Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareHistogenesis of Primary Motor Area of Fetal Cerebrum English0104Pandian MuthuchitraEnglish Sabnis AnjaliEnglish Shroff GautamEnglishIntroduction: Histogenesis of the fetal cerebrum can be useful in the treatment of Lisencephaly, Cerebral hypoplasia, Polymicrogyria and heterotopias which are sex-linked inherited disorders using the Targeted Drug Delivery system by Nanoparticles in in-utero in future. In the present study, we had measured the thickness of the cortical plate of the motor area in micrometre using Image J software. Aim: To study the thickness and number of layers in the primary motor area of the fetal cerebrum in different gestational ages. Material and Methods: Hundred cerebral hemispheres obtained from 50 fetal cerebrums were collected. These brains were obtained from fetuses ranging from the 17th week to the 40th week. The study was authorized by the Ethical Committee for Analysis of Research Projects. Cortical thickness of the motor area of both sides of the cerebrum was measured by Image J software after doing routine H & E stains. The number of layers was identified in different gestational ages of human fetuses. Results: The cortical thickness of the right motor area from 17th week to 40th week was 106.83 - 2298.19 micrometre and the left motor areas were from 111.14 – 2330.37 micrometre. At the 17th week, 3 layers were observed. 20th week 4 layers were observed, 22nd week 5 layers were observed and from 24th week onwards all the 6 layers were observed. Conclusion: The number of layers and cortical thickness increases with the increasing gestational age. By birth, the cerebral cortical thickness is approximately 2 mm. English Fetal cerebrum, Histogenesis, Cortical thickness, Lamination, Motor area, Gestational ageIntroduction:   The primary motor area of the cerebrum is of immense importance as it deals with motor control of the whole body. The histologically primary motor area is composed of six layers in adults. This complex structure of the primary motor area of an adult human cerebrum is formed from the fetal cerebrum through cellular proliferation, differentiation and migration. Histogenesis of the cerebral cortex (neocortex) - The layered structure of the adult cerebral cortex forms from the telencephalon as the surface area increases. At first, there are 3 zones to the cortex: 1) germinal zone, immediately surrounding the lateral ventricle, 2) intermediate zone, which becomes the white matter, and 3) marginal zone, which becomes the grey matter.1 Neuroblast of the germinal zone divides and migrate into the marginal zone to become neurons and glial cells.1 The marginal zone is formed by cells migrating a) early, which become the deeper layers of the cortex while those that migrate b) later, form the more superficial layers.1The neocortex represents the great majority of the cerebral cortex. It has six layers and contains between 10 and 14 billion neurons. The six layers of this part of the cortex are numbered with Roman numerals from superficial to deep.1 Layer I is the molecular layer, which contains very few neurons; layer II is the external granular layer; layer III is the external pyramidal layer; layer IV is the internal granular layer; layer V is the internal pyramidal layer, and layer VI is the multiform, or fusiform layer.1 Each cortical layer contains different neuronal shapes, sizes and densities as well as different organizations of nerve fibres. The cerebral cortex is the outer covering of grey matter over the hemispheres.1 It is typically 2- 3 mm thick, covering the gyri and sulci.2 Lamination is one of the hallmarks of the cerebral cortex.3 Despite the early recognition of this characteristic feature of cortical histology there is still little understanding of the fundamental organizing principle that governs it.4 It is not possible in the present state of the science to define the determinants of cortical cytoarchitecture”.5 We have yet to achieve a universal theory of cortical organization.6The motor cortex is an area of the frontal lobe located on the precentral gyrus that is involved in the planning, control, and execution of voluntary movement. In the present study, we are concentrating on the development of the number of layers and cortical thickness of grey mater from17th week to the 40th week of fetal gestational age. Material and methods: Hundred cerebral hemispheres from 50 fetuses ranging from 17th week to 40th week were collected from MGM Hospital after spontaneous abortions. After fixation of the fetal brain with formalin removal of brains was performed using a typical autopsy technique. The cerebrum was carefully removed from anterior to posterior by cutting the cranial nerves and spinal cord. Meninges were removed from the superolateral aspect of the cerebrum. The right and left cerebral hemispheres were separated by taking a cut on the corpus callosum. Inferior to the trunk of corpus extended the incision into the tela choroidea of the lateral and third ventricles, and the interthalamic adhesion connecting the medial surface of two thalami. The arachnoidal membranes and superficial vessels of the cerebral hemispheres were removed to simplify the identification of the sulci on the superolateral, medial and inferior cerebral surfaces. Fetal cerebral primary motor area tissues of both left and right sides were taken for block making and then for H/E stain. The development of layers and their cortical thickness in the primary motor area was observed and measured by image J software in a micrometre (Table- 1). The data is taken from the research study for PhD on “comparative study of microanatomy of fetal cerebrum of normal and eclamptic mothers”. The study was authorized by the Ethical Committee for Analysis of Research Projects. Specimens with congenital malformations and or structural damage were excluded. Result: The cortical thickness of the right motor area from 17th week to 40th week was 106.83 -2298.19 micrometre and the left motor area was from 111.14 – 2330.37 micrometre. In statistical analysis mean and standard deviation was calculated. At the 17th week, 3 layers were observed. The number of layers increased with increasing gestational age. 20th week 4 layers were observed, 22nd week 5 layers were observed and from 24th week onwards all the 6 layers were observed. Discussion:  In the present study on at 17th week, there appeared 3 layers in the cortical plate (Figure-1A, Table-2).   In layer I the cells are loosely packed and in layer III the cells are more tightly packed than layer II. At 20th and 21st weeks, 4 layers were seen (Fig. 1 B). In the book called “The development of the human neocortex,” it is written that the cortical plate is undifferentiated at the 4th and 5th months of gestational age.7 In the present study 5 layers were observed at 22nd and 23rd week (Fig.1 C) and from the 24th week onwards all the 6 layers were seen in the cortical plate (Fig. 1 D). It was observed that from the 6th month onwards all the 6 layers appeared in the cortical plate.7 Between 6 and 8 months 6 layers are observed in the marginal zone of the neocortex, recognized by cellular and fibre laminate.8 In the present study the 31st and 34th weeks show 6 layers in grey mater (Fig.2).             We had also measured the thickness of the cortical plate from the 17th week to the 40th week of both the right and left motor area of the fetal cerebral cortex. The cortical thickness was measured in micrometre by using image J software. The cortical thickness of the right motor area from the 17th week to the 40th week was 106.83 – 2298.19 micrometre and the left motor area was from 111.14 – 2330.37 micrometre (Table-1). The mammalian cerebral cortex primordial cytoarchitectural organization goes through four sequential stages, which, in order of appearance, are: the undifferentiated neuroepithelium (NE), the marginal zone (MZ), the primordial plexiform (PP), and the PCP appearance.9 At 11th-week fetal cortical thickness is 115 micrometre.7 At 15th-week fetal cortical thickness is 350 micrometres.9 The starting functional maturation of the deepest and older pyramidal neurons of the grey matter (PCP) establishes the first functional pyramidal cell stratum in the human motor cortex, which should correspond to layer V of the current nomenclature.9 By stage 20, the primordial plexiform lamina is well established, extends throughout the entire surface of the developing cerebral cortex, and is considered to be functionally active. It is, by this age, a superficial, 40 μm thick, complex fibrillar neuronal organization composed of numerous horizontal corticipetal fibres (demonstrable with silver methods), horizontal-bipolar Cajal-Retzius neurons and a few other, less defined, cellular elements.10  In the present study, the right motor area of the 20th week was 306.61 micrometre and the left motor area was 314.15 micrometre. It was observed that at the 20th week the length of the pyramidal neuron of stratum P1 is already 450 micrometers.9 The motor cortex grey matter thicknesses, including differentiated and undifferentiated pyramidal neurons, ranges between 400 and 600 micrometers.9 In the present study the right motor area of the 34th week was 1808.81 micrometre and the left motor area was 1895.3 micrometre. It was observed that at the 35th week the thickness of the motor area cortex grey mater ranges between 700 and 900 micrometres.9 In the present study the right motor area of the 40th week was 2298.19 micrometre and the left motor area was 2330.37 micrometre. The newborn primary cortex motor, already about 2 mm thick, is characterized by the abundance of pyramidal neurons.9 At birth, the human motor cortex grey matter thickness ranges from 1,500 to 1,700 micrometres.9 Before 28 gestational weeks the cortical plate was anechoic and a discrete layer from the underlying anechoic subplate zone, it was, therefore, inconspicuous on the sonographic image.11Any fetal CNS anomalies like Lissencephaly, intracranial hemorrhage, severe ventriculomegaly, microcephaly etc show abnormal cerebral lamination.11 Abnormal lamination will lead to abnormal migration of neurons which will, in turn, disturb the normal function of the brain. Conclusion:             The cortical thickness and number of layers in the primary motor area increase with the gestational age of the fetus on both sides. The proliferation of cells may increase the cortical thickness and number of layers in the primary motor area. Knowledge of thickness in the primary motor area may be useful to judge the thickness of the primary motor area of a newborn child in preterm delivery. This information may help to identify gestational lag while scanning fetuses of intrauterine growth retardation. Acknowledgement: Professor and head, OBGY Department, MGM Medical College, Dr. Sushil Kumar for permitting to collect fetuses from MGM Kalamboli hospital. Dr. Atul Deshmukh for helping us with using Image J software for measuring the cortical thickness. Conflicts of Interests: NIL Source of funding: NIL Contribution of authors: Dr. Pandian R. Muthuchitra1: Receiving and dissecting a fetal brain, making blocks and staining of slides, compiling data and statistical analysis. Dr. Sabnis S. Anjali2:  Interpretation of results and writing the article. Dr. Shroff A. Gautam3: Helped to get fetuses from OBGY department and interpretation of results. Englishhttp://ijcrr.com/abstract.php?article_id=4127http://ijcrr.com/article_html.php?did=4127 Malcolm B. carpenter, A.B. M.D. Neuroanatomy 4th edition. London Williams & Wilkins. Pg 390-391. Williams PL, Warwick R (eds): Gray’s Anatomy. Philadelphia: Saunders, 37th ed. Churchill Livingstone 1989. Pg. 1044. Braitenberg V cortical architectonics general and aerial. In: Brazier MAB, Petsche H (eds) Architectonics of the cerebral cortex. Raven, New York, 1978; 443- 465. Jone E. laminar distribution of cortical efferents cells. In: Peter A, Jones (eds) cerebral cortex,  vol 1. Plenum Press, New York, 1984; 521-553. Jones EG. Determinants of the cytoarchitecture of the cerebral cortex. In: Edelman GM, Gall WE, Cowan WM (eds) Signal and sense: local and global order in perceptual maps. Wiley, New York, 1990; 3–49. Rakic P, Singer W., Introduction. In: Rakic P, Singer W (eds) Neurobiology of the neocortex, report of the Dahlem workshop. Wiley, Berlin, 1988; 1–4. Altman J, Bayer S. Development of the human neocortex” A review and interpretation of the histological records, the laboratory of developmental neurobiology. Inc Ocala.  34481, USA 2015. Haldar A, Sahoo S, Chakraborty S, Banerjee P, Basu D. Cellular migration and histogenesis of the cerebral cortex with functional correlations in human fetuses at different weeks of gestation Int J Med Res. 2019;4(1): 51-54.  Marín-Padilla M. The human brain, prenatal development and structure.  Springer-Verlag Berlin Heidelberg. 2011. Miguel MP. Structural organization of the human cerebral cortex before the appearance of the cortical plate. Anat Embry. 1983;16(8): 21-40 Pugash D, Hendson G, Dunham CP, Dewar K, Moneys K, Prayer D. Sonographic assessment of normal and abnormal patterns of fetal cerebral lamination. Ultras Obstetgy. 2012; 40: 642-651.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareEffectiveness of Yogic Intervention in Non-Alcoholic Fatty Liver Disease: Case Series     English0508Panda Ashok KumarEnglish Palei DeeptiEnglish Mohanty Rakesh KumarEnglish Swain Dinesh Prasad SwainEnglish Prativa ShreeEnglishBackground: Non-Alcoholic Fatty Liver Disease (NAFLD) is most prevalent and projected as the state of disease and associated with metabolic syndrome high treatment cost. Regular exercise especially ‘Yoga’ is a preferable and economical preventive and curative measure in the management of NAFLD because there are no licensed drugs available for NAFLD and people embracing a sedentary lifestyle. Transient elastography (TE)provides the Liver stiffness measurement (LSM) used here as a marker of fibrosis in these NAFLD cases. Objectives: The objective of this case series was to evaluate the role of yoga in NAFLD patients without any medication. Methods: Three NAFLD patients identified retrospectively who had been prescribed yogic intervention without any medication. Result: This retrospective case series showed Kapalabhati Pranayama, Ardha matsyendrasana, Gomukhasana, Dhanurasana, Balasana and Dhyana (Meditation) are effective yogic interventions practised for 20 minutes in three NAFLD patients. This intervention can be corrected of blood sugar, blood lipids, elevated liver enzymes and liver fibrosis in studied three NAFLD patients Conclusion: This preliminary case series showed yogic intervention can useful in NAFLD. More studies are recommended. English NAFLD, Kapalabhati Pranayama, Ardha matsyendrasana, Gomukhasana, DhanurasanaIntroduction Non Alcoholic Fatty Liver Diseases (NAFLD) represents a spectrum of diseases from simple steatosis to fibrosis and is thought to be present in up to 70% of people with type 2 diabetes and obesity. The prevalence of NAFLD is to be around 9-32% in the general Indian population, with a higher incidence amongst overweight/obese and diabetic/ pre-diabetic patients.1 NAFLD is projected as the state of disease and associated with a doubling health care cost, need for liver transplantation; including raised death risk from cardiovascular disease, hepatocellular cancer, and other noncancer causes like liver Cirrhosis.2 Ayurveda medication is excellent, but limited evidence.3 Regular exercise especially ‘Yoga’ is a preferable and economical preventive and curative measure in the management of NAFLD because there are no licensed drugs available for NAFLD and people embracing a sedentary lifestyle.4 Yoga and Ayurveda are interlinked and yoga is one of the Indian philosophies that mean for self-improvement by gaining full potential of one’s body, mind and soul. Over ten years, Pranayama (breathing exercise), Asana (yogic posture), and dhyana (meditation) are very popular in clinical medicine for Non-pharmacological approaches in many non-communicable diseases. Yoga therapy has proven efficacy in obesity,5,6 prediabetic7 and can also correct liver function.8  Yoga therapy is beneficial in Alcoholic liver disease9 and Cirrhosis of the Liver10. The efficacy of Surya namaskar (sun salutation) on NAFLD is well studied with inconclusive result11.  Surya namaskar (sun salutation) is quite difficult to practice, therefore the efficacy of other yogic practices like- Kapalabhati Pranayama, Ardhamatsyendrasana, Gomukhasana, Dhanurasana, Balasanaand Dhyana (Meditation) in NAFLD is to be tested. Kapalabhati Pranayama is the type of rapid breathing technique to maintain homeostasis and well being. It can correct the functions of abdominal organs, purify blood and tone the abdominal muscle.12,13 Ardhamatsyendrasana(seated spinal twist)squeeze and twisting the intestines and liver, helpful in healing any damage caused by fibrosis, inflammation, and stress. It can correct the function of the Annavahasrotas (gastro-intestinal tract) and is thought to be an effective liver14. Dhanurasana(Bow pose) is a type of back bending posture to reduce belly fat and power to reverse the biological age and stimulate the abdominal organs.15 Gomukhasana(Cow face pose) is mentioned in Ghernda Samhita and Hatha Yoga pradipika, which can induce relaxation and alleviate fatigue. It stimulates the liver, pancreas and Kidney and prevents diabetics, low back pain. This pose can be practised for 30 seconds to one minute depending on the individual capacity for best therapeutic benefits and it can be increased gradually.16 Balasana (Child’spose) is one of the counter postures of dhanurasana (Bow pose) and maintain quality of life.17 Dhyana is the uninterrupted connection between the mind and the object chosen for meditation.18 The objective of the study- The objective of this case series was to evaluate the role of yogic techniques in NAFLD patients without any medication. Materials and Methods- We retrospectively identified three NAFLD patients who had been prescribed yogic intervention without any medication. The patients between the ages of 30-50 years were included and patients taking any medication were excluded from the study. Patient Information& clinical finding -Three patients were diagnosed sonographically. Among three patients, two were male and one female. All three patients were non-vegetarian. All patients complained of anorexia, indigestion and distension of the abdomen for more than three months. All patients having central obesity, overweight and BMI is more than 27 (Table no-1). Their viral hepatitis screening was negative antinuclear antibody, smooth muscle antibody, α1-antitrypsin, ceruloplasmin, and thyroid-stimulating hormone levels were within normal limits. All patients had elevated blood sugar, triglyceride and slightly elevated liver enzymes (SGOT & SGPT). The other liver enzymes and Platelet count were normal (Table no-2). All patients have elevated glucose levels. Timeline- The Specific Yoga asana and pranayama were practised under the guidance of a Yoga expert. The assessment was taken after 30days and after the completion of 90 days of intervention. Diagnostic assessment- The diagnosis of NAFLD requires evidence of hepatic steatosis by imaging or by histology. Ultrasound is very effective in diagnosis steatosis where more than 33% of hepatocytes are stenotic. Transient elastography (TE) provides the Liver stiffness measurement (LSM) using pulse-echo ultrasound as a surrogate marker of fibrosis. The Specific Yoga asana and pranayama for 90 days under the guidance of a Yoga expert. The important parameters before the commencement of the Yoga exercises (baseline values) and after the Yoga therapy were recorded.15-18 Yogic intervention–All the subjects within the yogic techniques were taughtKapalbhati pranayama, Yogasana and dhyana. The duration of practice was for 20 minutes from 7 A.M. to 8 A.M. It was advised to keep bowel and bladder emptied before yogic practice. The duration of Kapalbhati pranayama was 9 minutes approximately, that of asanawas9 minutes and dhyana 3 minutes approximately. Kapalbhatipranayamashould is practiced on an empty stomach. These studied patients were advised to sit comfortably with crossed leg position with straining of the back and hands should be rested on knees. Kapalavati is the exercise of contraction of the abdomen with forceful exhalation and inhalation. One stroke was completed with the completion of exhalation with inhalation. The patient begins with 30 strokes and ended with hundred eighty strokes.   After completing such 30 strokes inhale and exhale deeply and take a rest-pause of about 30 seconds. The patients were advised to keep their bodies steady without any movements of the head, shoulder and legs. This kapalabhati can be done for nine minutes. Two sitting asana like ArdhamatsyendrasanaandGomukhasana, two lie position of opposite body movement as DhanurasanaBalasana  and Dhyana, at last, were practised with a standard protocol( Table -3) Follow up and Result-The patient was followed up in 30days and 90days. The three patients have improved clinically and the radiological and biochemical parameters gradually developed during the period. After 30 days of treatment, their appetite appeared normal and got relieved abdominal discomfort, but no significant change in weight. The blood sugar and other parameter were slightly changed and significant change after three months of practice. The Ultrasound report of two patients became normal and change Midline stiff in fibro scan. There was a significant change in biochemical and radiological findings in all patients after three months(Table no-4) Result & Discussion-This present case series is a retrospective evaluation of 90 days of yogic intervention in a special protocol of kapalabhati, two sitting asana, two lay down asana and dhyana in three NAFLD patients. After 30 days of treatment, their appetite appeared normal and got relieved abdominal discomfort, but no significant change in weight. The blood sugar and other parameter were slightly changed and significant change after three months of practice. The Ultrasound report of two patients became normal and significant change in Midline stiffness in the fibro scan report. This yogic intervention is a preliminary report of the correction of liver fibrosis and elevated liver enzymes in three NAFLD patients. Although earlier two case reports were suggested that yogic intervention can stabilise SGOT and SGPT.11 This yogic intervention also corrected metabolism for which blood sugar, total cholesterol and serum triglyceride reduced significantly. Similar studies were found that yogic interventions have decreased fasting plasma glucose, postprandial blood sugar, total cholesterol, triglycerides and reduce weight. Kaphalbhati pranayama and dhyana are correct metabolic functions and heals the mind by reducing stress and anxiety respectively.19-22 KapalbhatiPrayanam(Breathing exercise) is aimed at pushing(exhaling) out air from the stomach as if it is pumping out toxins/negativity from the body. In NAFLD, oxygenation and blood flow are prevented by scar liver tissues. The liver becomes unable to filter toxins and perform its other vital functions leading to cirrhosis, liver failure, liver cancer. By practising the said yoga protocol, the liver gets stimulated, thereby ensuring that oxygen and blood flow freely through it. Management of weight and stress is quite important while dealing with any chronic illness like liver disease.23 Conclusion- This preliminary retrospective study reveals that yogic intervention can correct blood sugar, blood lipids, elevated liver enzymes and liver fibrosis of NAFLD patients. It will attract more Clinical trials in a high sample size. These Non-pharmacological interventions have more priorities and the potential to improve future clinical trials in NAFLD. This study will provide a more informative guide to patients and practitioners regarding Yogic intervention and Fatty liver. Widespread dissemination of this study will optimise the usefulnessYogic intervention in Fatty liver diseases. Acknowledgement – The authors acknowledged DG, CCRAS, vice-chancellor and Dean of Sri Sri  University and all participants of this study. Consent of patients -obtained Conflict of Interest -Nil No financial assistance was obtained from any sources. Author’s contribution AKP and DP conceived the idea of this case study and plan the study design. RKM, DPS and PSS have finalised the yogic intervention and guided the patients. All authors are involved in the study and drafting of the manuscript, revising and providing final approval for publication. Englishhttp://ijcrr.com/abstract.php?article_id=4128http://ijcrr.com/article_html.php?did=4128 Benedict M, Zhang X. Non-alcoholic fatty liver disease: An expanded review. World J Hepatol. 2017;9(16):715-732. Thomas G C , Mary R, Non Alcoholic liver disease 2020:The state of disease. Gatroenterology. 2020;158(7):1851-1864. Panda A.K, Hazra J. PotalaKaturohinyadiKwatha In KaphajaYakritDalludara (Non-Alcoholic Fatty Liver Disease): A Case Study. Int J Ayurv Pharma Res. 2020;8(11):1-8. Mishra AS, Sk R, Hs V, et al. Knowledge, Attitude, and Practice of Yoga in Rural and Urban India, KAPY 2017: A Nationwide Cluster Sample Survey. Medicines (Basel). 2020;7(2):8. Published 2020 Feb 5. doi:10.3390/medicines7020008 Gadham J, Sajja S,  Rooha S,  Effect of Yoga on obesity, hypertension and lipid prole Int J Res Med Sci. 2015 May;3(5):1061-1065 Bernstein AM. Yoga in the management of overweight and obesity. Am J Life Med. 8.1 (2014): 33-41. Jyotsna VP. Prediabetes and type 2 diabetes mellitus: Evidence for the effect of yoga. Ind J End Met.2014;18(6): 745. Sharma K. Krishna E. A study on the Effect of Yoga Therapy on Liver functions. Eur Sci J.2014; 10:62-65. Naveen GH, Nithin K, Selva KG, Management of Alcoholic Liver Disease by Naturopathy and Yoga Intervention: A Case Report. Int J Yoga Allied Sciences (ISSN: 2278 – 5159) 2014;3(2): 2014 Reva. S, V. Kavitha, A. Mooventhan. Effect of Yoga and naturopathy on the liver, renal and cardiorespiratory functions of patients with hepatic cirrhosis with portal hypertension. J Compl Integ Med.(2017);15(4):1-6. DOI: https://doi.org/10.1515/jcim-2017-0098 KayelarasiC.A. &VenkateswaranST. Efficacy of Surya namaskara on NAFLD patients-A Interventional study, Dissertation of The Tamilnadu Dr MGR Medical University, Chennai. 2016-2019. Dinkar RK. Effect of Kapalabhati Pranayama on body mass index and abdominal skinfold thickness. Indian Med Gaz. 2013;11:424-426. Ansari RM. Kapalabhati pranayama: An answer to modern-day polycystic ovarian syndrome and coexisting metabolic syndrome?. Int J Yoga. 2016;9(2):163-167. doi:10.4103/0973-6131.183705. Nitin S M, Desai P, Role of Ardha-Matsyendrasana on the disease of Annavahasrotas in perspective of Sharira. Int Ayu Med J. 2016;3453-3460. Jason S, Rana A, Yadav S.K An Anatomical Exploration of “Dhanurasana’’ Int J Trend Sci Res Devp. 2020;4(4):5-11. URL: https://www.ijtsrd.com/papers/ijtsrd30878.pdf McCall, Marcy C. How might yoga work? An overview of potential underlying mechanisms. J Yog Phys Ther. 2013; 3(1): 1. Joshi LN, Effect of selected yoga asana on quality of life of CLBP patents. Eur J Physical Educ Sport. 2017;3(1):105-113.  Telles S, Singh N, Gupta RK, Balkrishna A. A selective review of dharana and dhyana in healthy participants. J Ayurveda Integr Med. 2016;7(4):255-260. doi:10.1016/j.jaim.2016.09.004 Mondal S, Kundu B, Saha S. Yoga as a Therapeutic Intervention for the Management of Type 2 Diabetes Mellitus. Int J Yoga. 2018;11(2):129-138. doi:10.4103/ijoy.IJOY_74_16 Seo DY. Yoga training improves metabolic parameters in obese boys.  Kor J Phys Pharm. 16.3 (2012): 175-180. CAP RYT. A narrative review of yoga intervention clinical trials including weight-related outcomes. Alter Ther Health Med.  2013; 19(3): 32-35. Mungal S, Bondade A, Effect of Sudarsana kriya yoga on lipid profile, Int J Curr Res Rev. 2013;5(19):49-55. https://www.ourpositivestory.com/the-best-yoga-for-liver-cirrhosis-fatty-liver-and-hepatitis-a-b-c-d-e/

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareAdiponectin to Resistin Ratio concerning Insulin Resistance in Different Phenotypes of PCOS in Indian Population English0913Chaitali MEnglish Ramesh CGEnglish Raj REnglish Achal ACEnglishEnglishPCOS, Insulin Resistance, Adiponectin, Resistin, Adiponectin: Resistin RatioIntroduction: The first recorded observation of polycystic ovarian syndrome was described in 1935 by stein & Levinthal .1His Syndrome is an exceptionally common endocrine disorder in women of reproductive age. Amenorrhea, hirsutism, obesity, and ovaries with a gross polycystic appearance are the common manifestation of the disease. Initially, the diagnosis of PCOS was under controversy primarily because of its heterogeneous manifestations. Even these manifestations appear to change alter during the lifetime of the patient.2 There have been several attempts to make a consensus for the diagnosing criteria of this condition. After the 55 years of the first description of the syndrome in 1990, an initial consensus was obtained in the conference held by the National Institute of Child Health and Human Development (NICHD). Two criteria were found to be at the centre of the disease, 1) clinical and/or biochemical hyperandrogenemia; and 2) oligo- or anovulation, with the exclusion of other known disorders.3Later it is realized that the spectrum of PCOS is much broader than it was initially thought of and another need for the consensus on diagnosing criteria for PCOS was felt. In 2005 Rotterdam, Netherlands the diagnosing criteria were revised and termed as Rotterdam Criteria. The fulfilling of two of the following three features prescribed by the Rotterdam Criteria are considered as the cause of PCOS. Three identified features of Rotterdam criteria is 1) oligo- or anovulation; 2) clinical and/or biochemical hyperandrogenemia, and 3) PCO-Ultra Sound with the exclusion of other etiologies as mentioned in the NICHD criteria. Rotterdam criteria gave 4 identifiable phenotypes of the disease. Several Studies reported that PCOS is characterized by hyperinsulinemic insulin resistance 4 independent of obesity.5 Functional ovarian hyperandrogenism due to dysregulation of androgen secretion results in PCOS.6Studies show that there is an intensive relationship between Insulin & gonadal function. In animal models, it was researched that insulin signalling through theca cell insulin receptor results in hyperandrogenic anovulation .7 Excess Insulin up-regulates LH binding sites and enhance steroidogenesis in response to LH.8,6 Obesity plays a major leading to this endocrinological disorder via insulin resistance, while gonadotropin production is suppressed due to production of testosterone from circulating androstenedione .5 Bioavailability of testosterone also increase due to obesity-induced decrease in Sex hormone-binding globulin (SHBG) production.9 The expanded fat mass in obesity does not only act as the store for enormous energy but also act as an endocrine organ with a massive supply of adipokines/cytokines.10 Leptin, Adiponectin and Resistin have widely studied adipokines about PCOS.11Adiponectin has an insulin-sensitizing role and thereby alters glucose metabolism, exhibits anti-inflammatory and antiatherogenic properties.12 On the Other hand Resistinhas Insulin antagonising function. The favourable effect of adiponectin on whole-body metabolism is accepted and it is seen that circulating adiponectin shows an inverse correlation with adiposity.12Metabolic and cardiovascular diseases state normally shows hyper adiponectinemia. Low levels of adiponectin pave the way for insulin resistance and myocardial infraction therefore it may be considered as one of the causative elements of these disorders.13Cysteine rich protein Resistinis secreted primarily by white adipocytes as 94 amino acid polypeptide and circulating levels raised by obesity either genetic or diet-induced.14  PCOS shows disturbed adipokine secretion along with aberrant morphology of adipose tissue which has been linked with insulin resistance.15 PCOS exhibit significantly lower Adiponectin levels compared to weight-matched obese control. 16 Objective of the study is to observe the variation of the ratio of Adiponectin to Resistin in different phenotypes of PCOS with relation to insulin resistance. Materials & Method The study was conducted in the Department of Biochemistry, Mayo Institute of Medical Sciences, Barabanki, India. 144 female subjects diagnosed with PCOS aged between 18 – 40 years were chosen from the OPD of Obstetrics and Gynecology department of Mayo Institute of Medical Sciences, Barabanki India. These subjects were already diagnosed with PCOS as per Rotterdam criteria for that they underwent clinical examination, Sonography, Biochemical and Hormonal Assays. Subjects were categorized into four different phenotypes of PCOS, A) PCOS complete fulfilling all three criteria (PCO-COM), B) PCO on ultrasound with oligo or anovulation (PCO-O), C) anovulation with hyperandrogenism (O-HA) and D) PCO with hyperandrogenism (PCO-HA). Subjects less than 18 yrs and more than 40 yrs of age, with late-onset congenital adrenal hyperplasia, thyroid disease, hyperprolactinemia, androgen-secreting tumours were excluded from the study. Subjects using medication (including Oral Contraceptives), a hormonal intrauterine device and pregnant or lactating subjects were excluded from the studies. The study was approved by the institutional ethical committee and written informed consent was obtained from all participants. waist and hip circumference were recorded for all the subjects to calculate Waist Hip ratio (WHR). An overnight fasting blood sample was collected for the estimation of biochemical parameters. Enzyme-linked Immunosorbent Assay method was used for estimation of serum Insulin, Adiponectin and Resistin levels. Human Insulin ELISA Kit, Diameter, Italy, Adiponectin Elisa kit, Demeditec, Germany, Human Resistin Elisa kit, Sincere Biotech China were used for the study. Homeostasis Model Assessment (HOMA) was calculated for the estimate of Insulin Resistance. Statistical Analysis: Data were analyzed using Microsoft Excel 365 Statistical plugin software & statistical package provided by www.stats.blue. Results are expressed as Mean, Standard Deviation. ANOVA with Post hoc Tukey pairwise multiple comparison test and regression analysis were performed with data obtained. Results were considered statistically signifi­cant whenever p< 0.05. Results: Baseline observations of the subject population (Table 1) showed WHR was greatest among the group O-HA and lowest for the group PCO-O. HOMA-IR variation was observed among groups and a maximum value was obtained of 2.4in the A-HA group and a minimum of 1.3 for the PCO-HA group. A: R ratio was found to be highest among the PCO-HA group and lowest for O-HA. ANOVA results for A: R RATIO for the groups shows that the variance is significant (F = 329.258, F>0, p = 0) (Table 2). Post hoc Tukey pairwise multiple comparison tests (Table 3)shows the difference between the groups is significant. A: R ratio values decreases as PCO-HA>PCO-COM>PCO O> O-HA among the groups.  Linear regression analysis shows that there is a significant moderate negative association between HOMA IR and A: R Ratio ( r= -0.41, p= 0.000). Significant moderate association also observed between WHR&A:R ratio (r = - 0.34, p = 0.000).  Between HOMA IR &WHR, the former shows a stronger association with A: R Ratio (Table 4). Discussion Obesity is often measured by BMI despite the fact it may not necessarily be the most accurate measure of adiposity.17BMI do not describe the proportion of lean versus adipose tissues related to morbidity and mortality in clinical scenario.18 WHO guidelines also admit that Waist Hip ratio is a better predictor than BMI for assessment of abdominal adiposity.19Obesity is the leading determinant factor for cardiovascular complications among women with PCOS.20 In our study we observed that O-HA group having the maximum WHR thus visceral fat. our observation also depicts that insulin resistance is also found to be maximum in O-HA phenotypes and supports the theory that insulin resistance is a consequence of obesity among PCOS patients.21 Obesity and Adiponectin has an inverse relationship and seems to have a significant role in the pathophysiology of PCOS.22  Level of Serum Adiponectin in PCOS is controversial. Serum Adiponectin values were found to be lower than the control15whereasevidence are there to suggest that it didn’t differ among PCOS and healthy controls.23  Between Obese and non-obese PCOS patients Adiponectin levels were found to be lower in the former group.24 Resistin on the other hand performs its function as a paracrine and endocrine molecule. Resistin is believed to have an inhibitory effect on insulin signalling.25  Serum Resistin level in PCOS is also controversial and data with varied conclusions are available.10  Here authors are willing to suggest that it may be because the levels of Adiponectin and Resistin are not studied among the different phenotypes (Rotterdam Criteria) but most of the studies included PCOS as a whole without considering the phenotypes. Our study shows the Serum Adiponectin and Resistin level varies among the 4 phenotypes of Rotterdam criteria. Adiponectin /Leptin ratio and Adiponectin/Resistin Ratio was found to be significantly lower in women with PCOS when compared to normal control.26 The ratio is significant for both obese and non-obese PCOS pools. Adiponectin/Resistin ratio negatively correlated with HOMA IR.26 Our study reiterates the findings. Study also observed that the ratio of Adiponectin /Resistin ratio significantly differs among the study of the phenotype. A: R ratio was found to be significantly associated with Insulin resistance and WHR. Conclusion In conclusion, we would intend to suggest Adiponectin /Resistin as a sensitive parameter for different phenotypes of PCOS. Our study lacks in the estimation of actual fat content and used WHR as a proxy for adiposity. A large sample size with diverse backgrounds is required to understand the actual mechanism behind the pathophysiology of different manifestations of PCOS. Acknowledgement: The authors acknowledge the immense help received from the management of Mayo Institute of Medical Sciences and Nims University for providing the infrastructure for this research. The authors also acknowledge the help from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Source of Funding: Self-financed research project Conflict of Interest: The study has no conflict of interest Authors’ Contribution: All the authors contributed to this article significantly Author 1: Designing, data collection, data analysis, article writing Author 2: Designing, data verification, article editing Author 3: Data collection, article writing Ethical Clearance Letter No.: The study was approved by the   Institutional Ethics Committee vide approval letter no. MIMS/Ex/2019/199 dated 19/11/19 Englishhttp://ijcrr.com/abstract.php?article_id=4129http://ijcrr.com/article_html.php?did=4129 Shroff R, Syrop CH, Davis W, Van Voorhis BJ, Dokras A. Risk of metabolic complications in the new PCOS phenotypes based on the Rotterdam criteria. Fertil Steril. 2007;88(5):1389–1395. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005;352(12):1223–1236. Zawadzki JA, A. D. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. Dunaif A, Givens JR, Haseltine FP, Merriam GR, editors. Boston: Blackwell Scientific; 1992. 377–384 p. Nestler JE. Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications. Semin Reprod Endocrinol. 1997;15(2):111–122. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33(6):981–1030. Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37(5):467–520. Wu S, Divall S, Nwaopara A, Radovick S, Wondisford F, Ko C, et al. Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell. Diabetes. 2014;63(4):1270–1282. Endoh A, Kristiansen SB, Casson PR, Buster JE, Hornsby PJ. The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenases. J ClinEndocrinolMetab. 1996;81(10):3558–3565. Anderson A, Solorzano C, McCartney C. Childhood obesity and its impact on the development of adolescent PCOS. Semin Reprod Med. 2014;32(03):202–213. Chen X, Jia X, Qiao J, Guan Y, Kang J. Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome. J Mol Endocrinol. 2013;50(2): R21-37. Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J ClinEndocrinolMetab. 2008;93(11 Suppl 1):S64-S73. Ziemke F, Mantzoros CS. Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr. 2010;91(1):258S-261S. Deng Y, Scherer PE. Adipokines as novel biomarkers and regulators of the metabolic syndrome: Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci. 2010;1212(1): E1–E19. Farshchian F, RamezaniTehrani F, Amirrasouli H, Rahimi Pour H, Hedayati M, Kazerouni F, et al. Visfatin and resistin serum levels in normal-weight and obese women with polycystic ovary syndrome. Int J Endocrinol Metab. 2014;12(3):e15503. Mannerås-Holm L, Leonhardt H, Kullberg J, Jennische E, Odén A, Holm G, et al. Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance. J Clin Endocrinol Metab. 2011;96(2): E304-E311. Glintborg D, Andersen M, Hagen C, Frystyk J, Hulstrøm V, Flyvbjerg A, et al. Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls. Eur J Endocrinol. 2006;155(2):337–345. Mukherjee D, Ojha C. Obesity paradox in contemporary cardiology practice. JACC CardiovascInterv. 2017;10(13):1293–1294. Prado CMM, Heymsfield SB. Lean tissue imaging: a new era for nutritional assessment and intervention: A New Era for nutritional assessment and intervention. JPEN J Parenter Enteral Nutr. 2014;38(8):940–953. Nishida C, Ko GT, Kumanyika S. Body fat distribution and noncommunicable diseases in populations: an overview of 2008 WHO Expert Consultation on Waist Circumference and Waist-Hip Ratio. Eur J Clin Nutr. 2010;64(1):2–5. Shen S-H, Shen S-Y, Liou T-H, Hsu M-I, Chang Y-CI, Cheng C-Y, et al. Obesity and inflammatory biomarkers in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod  Biol. 2015;192:66–71. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989;38(9):1165–1174. Escobar-Morreale HF, Villuendas G, Botella-Carretero JI, Alvarez-Blasco F, Sanchón R, Luque-Ramírez M, et al. Adiponectin and resistin in PCOS: a clinical, biochemical and molecular genetic study. Hum Reprod. 2006;21(9):2257–2265. Lecke SB, Mattei F, Morsch DM, Spritzer PM. Abdominal subcutaneous fat gene expression and circulating levels of leptin and adiponectin in polycystic ovary syndrome. Fertil Steril. 2011;95(6):2044–2049. Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP, et al. Complex distribution, not the absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem. 2004;279(13):12152–12162. Shen YH, Zhang L, Gan Y, Wang X, Wang J, LeMaire SA, et al. Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK stress signal-induced inhibition of insulin signalling. A cross-talk between stress signalling and insulin signalling in resistin-treated human endothelial cells: A cross-talk between stress signalling and insulin signalling in resistin-treated human endothelial cells. J Biol Chem. 2006;281(12):7727–7736. Sarray S, Madan S, Saleh LR, Mahmoud N, Almawi WY. Validity of adiponectin-to-leptin and adiponectin-to-resistin ratios as predictors of polycystic ovary syndrome. Fertil Steril. 2015;104(2):460–466.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareKnowledge Discovery in Protein Sequence Analysis Using Hierarchical Clustering Method English1416Desai FarhanaEnglishIntroduction: New Data Mining techniques play a very important role in the large growing biological databases. The clustering technique is an unsupervised method in data mining. Hierarchical Clustering techniques are useful to represent relationships between protein families. Objective: Bioinformatics urges the need of discovering knowledge in the vast area of molecular biology by using data mining as the core. Data Mining aims to discover hidden data from a large volume of data. Method: This paper discusses the hierarchical clustering technique of data mining on protein sequence datasets to identify genes that are consistent, easy to implement, finding and grouping the number of clusters pattern recognition. However, the valuable data is sometimes not useful but the knowledge hidden in that valuable data is meaningful. Result: The distance is used to determine how closely two organisms are related, whereas the dendrogram shows a graphical representation of the distance calculated between the clusters. Conclusion: The hierarchical clustering will help the biologist to judge which genes were clustered rightfully by viewing the tree structure. e the dendrogram. Therefore, the main aim is to unfold the knowledge in the vast field of bioinformatics by using information technologies as the key. English Clustering, Phylogenetic tree, Sequence, Hierarchical clustering, Pattern, DendrogramINTRODUCTION Bioinformatics and data mining provide exciting research challenges for computational science. Data Mining is the process of knowledge discovery of various patterns from a sea of data whereas Bioinformatics involves the storage, analysis, and construction of information from biological data in the form of sequences, pathways, and gene expression. New Data Mining techniques play a very important role in the large growing biological databases. Many times Data Mining is also known as Knowledge Discovery, which means searching a large volume of data to discover patterns and new trends that go beyond simple analysis.1 The Clustering technique is an unsupervised method in data mining.2 It helps to improve the accuracy of the data. A phylogenetic tree can be build-using Hierarchical clustering for known corresponding protein sequences or DNA sequences. A Phylogenetic tree is useful for biologists in solving both scientific and practical problems. The problems would be stated as an evolution of complex features of the species, prediction about fossils, the evolution of diversity, etc. Hierarchical Clustering techniques are useful to represent relationships between protein families. There are two types of hierarchical clustering methods Agglomerative (bottom-up) and Divisive clustering (top-down). Using agglomerative clustering the very first single cluster is chosen and further in recursive fashion two or more relative clusters keep on merging. Divisive clustering starts with all data points merged in one cluster and further splits into most relative clusters recursively. Cluster analysis is a method for finding similar data objects present in the data.3This method divides the section into sets of clusters in such a way that two objects a picked, which resembles similar from the same cluster, whereas clusters, which belong to different clusters, are not similar. METHODOLOGY The process of data mining is part of many steps, which require repetition and refinement to achieve accuracy. Finding out new methods of Data Mining will act as a key factor in the vast mounting of biological data. It is a key point to state that the whole process of Data Mining covers a gathering of many techniques [Fig. 1], which involves finding the pattern from a large set of sequences, applying a hierarchical clustering algorithm and discovering knowledge through the result, which is a phylogenetic tree.   CONCLUSION The phylogenetic tree is compared against the problem if it is solved with a single phylogenetic tree then there is no recursive procedure to be followed else the data is changed and the hierarchical clustering steps are executed to get the right phylogenetic tree.4 The data is collected from a distance matrix [Fig. 2] on which the hierarchical clustering method is applied.5 The output of Hierarchical clustering is a dendrogram that is built from a  cluster hierarchy or,  in a different way,  a  tree of clusters.  Each cluster node arises from child clusters;  sibling clusters extract the points roofed by their common parent.  Such a method allows discovering data on various granularity levels.  The process continues in this form until the requested number of clusters i.e. a constant k is achieved.  RESULTS The closest clusters were displayed through the hierarchical clustering algorithm as follows: The closest Clusters are: C, DE:: 45 A, B:: 20 AB, CDE:: 72 D, E:: 30 The distance is used to determine how closely two organisms are related. The line that connects all other lines is the representation of the common ancestor.  Fig.3 describes the dendrogram generated from the distance matrix. DISCUSSION A dendrogram is a cluster tree, which is used to represent sequence data providing links to various groups. Each group is connected to a similar group and ends up forming a tree-like structure. The above figure shows the results of a hierarchical cluster analysis of the sequence. The horizontal axis shows the distance between each cluster, in which four clusters were identified with an optimal number of 2–4nodes in each cluster. Cluster 1 is a combination of A and B, which are the closest cluster with a distance of 20. The next closest found is D and E with a distance of 30. The common factors for C and (D and E) are grouped in Cluster 3, whereas Cluster 4 is a combination of (A and B) and (C and (D and E)). This information, which is divided amongst the nodes, has a huge impact on the selection of the closest cluster. The advantage of hierarchical clustering helps the biologist to judge which genes were clustered rightfully by viewing the tree structure. e the dendrogram. It also enables us to predict how the genes will change in the future. Phylogenetics provides a more accurate description of patterns based on sequence data. Acknowledgement: I am thankful to Dr. Acharya for productive discussion in the field of bioinformatics and computer science. Sir, guided me to include the best of computer skills in the study of bioinformatics. I also thank my Institute colleagues for their healthy discussion that supported my research. Conflict of interest: The author declares that there are no competing interests Source of Funding: No source of funding Authors’ Contribution: The author has proposed the approach and has also read and approved the final manuscript Englishhttp://ijcrr.com/abstract.php?article_id=4130http://ijcrr.com/article_html.php?did=41301. Vinothini B, Shobana D, Nithyakumari P. Application of Data mining in the Field of Bioinformatics. Int J Trend Res Dev. 2016. 3(1):21-3. 2. Ali Masood M, Khan MNA. Clustering techniques in bioinformatics. I.J. Modern education and computer science.Int J Med   Curr Sci. 2015; 1:38-46. 3. Murugananthi C, Ramyachitra D. Performance evaluation of partition and hierarchical clustering algorithms for protein sequences. Int J Comp Intell Inform Int J Curr Infor. 2014;3(4):272-7. 4. Staton JL. Understanding phylogenies: constructing and interpreting phylogenetic trees. J South Car Acad Sci. 2015;13(1):24-9. 5. Desai F, Kamat RK. Calculation and visualization of the phylogeny of clusters using java API (application programming interface). J Eng Appl Sci. 2017;12(11):2827-30.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareComparative Efficacy and Tolerability of Luliconazole versus Terbinafin in Pediatric Patients-A Randomized Trial English1722Harinkhere Sanjay KumarEnglish Arya Raj KumarEnglish Garg AnubhavEnglish Ranjan K. P.English Kothari SarojEnglishAim/Objective: Luliconazole is a newer imidazole antifungal drug effective against a variety of fungal infections, especially dermatophytosis, which is one of the most common superficial fungal infections, caused by dermatophytes. The present study is designed to compare the efficacy and tolerability of topical antifungal drug luliconazole with terbinafine used for the treatment of a variety of fungal infections, especially dermatophytosis. Materials and Method: In this perspective, the observational and open level study randomly selected patients (those fulfilling the inclusion criteria) are categorized according to diagnosis and had been advised to apply topically the respective drug during the study period. Results: In the present study we found that the luliconazole was more efficacious and tolerable than terbinafine at a short term therapy. Conclusion: Luliconazole was better efficacious and tolerable than terbinafine in relieving signs and symptoms of dermatophytosis, especially pruritus and desquamation. EnglishDermatophytosis, Efficacy, Pruritus, Tolerable, Dermatophytes, DesquamationIntroduction: Fungal infections are a major health problem all over the world and an important cause of morbidity and may be categorized as superficial or invasive. Superficial fungal infections are primarily caused by dermatophytes, Candida spp, and Malassezia species affects 20%–25% of the world’s population and are associated with interference with daily activities, poor quality of life, and health care expenditure.1Invasive fungal infections are usually appearing in the presence of one or more predisposing factors, especially in immune-compromised patients. Systemic fungal infections are an important cause of hospitalization and may even cause mortality. Dermatophytes are aerobic fungi and physiologically can digest keratin for their growth as they replicate in the superficial layers of the epidermis. Consequently, in clinical practice, hairs, nails and skin are mostly affected by dermatophytes infection due to rich keratin content. The continued existence of embedded arthroconidia (fungal element) for years in scales of hair and skin leads to frequent recurrence or relapse. These dermatophytes belong to three genera, i.e., trichophyton, microsporum, and epidermophyton. Although there is no standard definition of chronic dermatophytosis in literature at far patients with a duration of disease more than 6 months to 1 year, with or without recurrence, despite being treated with an adequate course of antifungal drugs are considered as chronic dermatophytosis. Recurrent dermatophytosis is defined as the reoccurrence of infection within few weeks of stopping the treatment.2 The lesion of dermatophytosis is present with an annular or ring-shaped red scaly plaque with central clearing, often associated with severe pruritus. Pruritus often leads to an intense desire to itch; affecting the quality of life of the patients and secondly, intense itching of a lesion increases the chance to develop a secondary bacterial infection. Inappropriate use of topical steroids results in unclear morphology of fungal infections. The clinical manifestations of dermatophytosis differ according to the site of infection and the patient’s immunologic response. Genetic susceptibility is also identified to affect the predisposition to dermatophytic infections.3 The commonest presentation is Tinea pedis, also known as dermatophytosis of the feet, caused by Trichophyton rubrum. The next most common fungal infections caused by T. rubrum, T. mentagrophytes, and Epidermophyton floccosum areTinea cruris and Tinea corporis. Onychomycosis i.e. invasion of the nail plate can be due to dermatophytes, candida, or non-dermatophytic moulds. Historically, the term medical mycology, specifically related to human fungal diseases, began with the discovery of the fungal aetiology of favus. According to Seeliger.4 However, Robert Remak recognized that the etiologic agent of favus was infectious. He cultured it on apple slices, and authentically described it as Achorionschoenleinii, in honour of his mentor and his initial discovery.5 Etothrix invasion of the beard and scalp by Microsporum, which is referring to the small spores around the hair shaft; audouinii, and endothrix hair invasion by Herpes (trichophyton) tonsurans.5 In addition to his observations on dermatophytes, he also explained the clinical and microscopic appearance of thrush in children5 Sabouraud’s treatment of tinea capitis by a single-dose, single-point roentgenology epilation achieved cures in 3 months in contrast to the current therapy of manual epilation and topical application of medications.6 Systemic or topical antifungal drugs are used as treatment strategies to deal with fungal infections. Antifungal drugs interfere with the biosynthesis of ergosterol which is an integral component of the fungal cell membrane and cell wall, thus causing inhibition of fungal growth and replication. Though, their action on different enzymes in the same pathway probably results in different properties and degrees of efficacy. Allylamines are squalene epoxidase inhibitors; act early in the ergosterol biosynthesis pathway with resulting accumulation of squalene compound that is toxic to the fungal cell membrane thus responsible for the fungicidal activity of allylamines. They have very good efficacy against Trichophyton spp. however only fungistatic action against C. albicans and M. furfur. Amorolfine is a morpholine antifungal compound, has strong activity against Trichophyton spp., C. albicans, and M. furfurthat acts by inhibiting both C14 reductase and C7–C8 isomerase activity.7 The azole antifungal drugs act by inhibiting 14α-lanosterol demethylase and have strong activity against C. Albicans and Trichophyton spp. As a consequence, lanosterol accumulation has a less toxic effect than squalene, so imidazoles have a fungistatic action.8 The efficacy of topical drugs in the treatment of superficial mycoses depends not only on the type of lesion and mechanism of action of the drug, but also on the viscosity, hydrophobicity, and acidity of the formulation as well and its distribution and retention in the stratum corneum. Regardless of the type of formulation, penetration of topical agents in hyperkeratotic lesions is often doubtful.9 Materials and Methods: The present prospective, observational and open-label study was conducted in the department of pharmacology in association with departments of microbiology and skin & VD, Gajra Raja Medical College and associated J.A. Group of Hospitals, Gwalior from a period of March 2018 to May 2019 after getting clearance from institutional ethical clearance letter No. Bio/MC/Ethical/555 dated 10/04/2018. A total of 100 clinically diagnosed dermatophytosis patients with the age ranges from 1 to 12 years, who fulfilling the inclusion criteria were randomly selected for the study after taking written informed consent. The inclusion criteria consist (1) Patients had an age between 1-12 years, (2) Both male and female were included, (3) those are positive by mycological (10% KOH mount) examination, (4) those patients who apply the medication for the recommended duration of therapy. The exclusion criteria consist (1) Patients below the age of 1 year and above the age of 12 years, (2) those patients who were taking immunosuppressant or corticosteroid therapy either orally or topically, (3) those patients who were receiving oral/topical other antifungal drugs, (4) patients having known history of hypersensitivity with terbinafine and luliconazole, (5) chronically ill patients, and (6) patients who were failed to follow-up for two consecutive visits. Clinically diagnosed Selected patients were grouped in Group A and Group B and treated with 1% luliconazole cream and terbinafine cream respectively and were instructed to apply for respective medicine over the affected part twice daily for 2 weeks. Clinical assessment was based on pruritus, erythema and desquamation on the affected lesion and graded accordingly. The mycological assessment was based on KOH and culture mounting of the specimen. Visual Analogue Scale (VAS) is a method, was used to assess the severity of pruritus.11      VAS grading: 0 – No Pruritus 1-3 – Mild Pruritus 4-7  – Moderate Pruritus 8-10 – Severe Pruritus Specimens were collected from the margins of the lesion by skin scraping and scales following all the aseptic precautions and then transported aseptically in the department of microbiology within 1-2 hours of collection, for mycological examination to confirm the infection. In the microbiology department, a 10% KOH mount slide of the specimen was made to see fungal hyphae under low (10X) and high power (40X) consecutively followed by culture on SDA with or without antibiotic media at 37oc for 48 hours incubation. After 48 hours, morphological identification of fungal isolates was done by Gram’s stain, LPCB (Lacto -phenol cotton blue) mount and slide culture. At the end of the study mycological examination was performed to ascertain the mycological cure. Patients were asked for any adverse reaction and effectiveness (relief from symptoms) of the drug during each visit.   All the data of total patients taking luliconazole and terbinafine including age group, sex, clinical feature, diagnosis, cure and adverse reactions to the respective drug was collected and tabulated. Data are summarized and compared statistically by frequency distribution and percentage proportion. Chi-square test and students t-test was applied to know the significant (p-value) ratio of difference statistically by using software IBM SPSS. Results: Out of total enrolled 100 patients, 79 patients with the age ranging from 1-12 years and fulfilled the inclusion criteria were included for the study statistically significant p-value:0.009616 as shown in Figure no.1, while rest 21 patients were fails to do regular follow up and were excluded from the study. In the present study, among the selected patients male patients contributes (n=44, 55.7%) and female (n=35, 44.3%) with male: female ratio was 5:4,statistically insignificant p-value:0.254286 as shown in Figure no.2. In the present study, cases were categorized according to diagnosis which shows that infection by Tinea corporis (59.5%) was commonest among the other species of tinea while only n=4 (5.1%) patients were showed infection by Tinea pedis. Data were summarized in Table no.1 / Figure 3 statistically significant p-value: 0.000001. In the present study patients treated with luliconazole antifungal cream (group A) were n=41/79,51.9%; while those treated with terbinafine were n=38,48.1% as shown in Fig 4. In the present study, we found that pruritus and desquamation were significantly reduced in patients treated with luliconazole (n=40/41) than terbinafine (n=27/38 and n=22/38 respectively) p=0.04 and p=0.005. Erythema was almost completely disappeared by luliconazole (n=41/41) than terbinafine (n=25/38) p=0.02. Data are summarized in table no 1. In the present study, we found that only n=5 /79, 6.33% of patients were reported with adverse drug reactions, which is more in terbinafine n=3/79 than luliconazole group n=2/79. Data is summarized in Figure no.5 statistically significant p-value: 0.000001. Discussion: Dermatophytosis is one of the earliest known fungal infections of humans and affects the world population.12 Although dermatophytosis does not cause mortality, it does cause morbidity especially in tropical countries like India due to its hot and humid climate.13  No race in the world is entirely free from dermatophytosis,14 as the degree of immunosuppression and the numbers of immunosuppressed patients are increasing at a speed; the management of dermatophytosis would be a big challenge in the years to come. It affects the quality of life of a patient due to the associated inflammatory symptoms mainly pruritus. Recurrence of tinea infections is common due to inadequate treatment or re-infections, especially of the intertriginous areas. In the present analysis based on data of 79 evaluable patients, both the study drugs showed a significant reduction in signs and symptoms (pruritus, erythema, and desquamation) of tinea infections as compared to baseline. At the end of the ‘Treatment Phase’ greater proportion of patients in luliconazole group had absence of pruritus (98%) and erythema (100%) as compared to terbinafin. In our study we found that luliconazole is more efficacious and safe compare to terbinafin in relieving the symptoms of dermatophytosis. A similar review study carried out by Khanna D et al.10 and Gupta A et al.15, both demonstrated that luliconazole is more efficacious than terbinafin which support the result of our study. In contrast to our study; a separate study carried out by Ghannoum MA et al.16 demonstrated that terbinafine is more efficacious than luliconazole. In the present study, we found that the overall symptoms cure rate (composite score) of luliconazole was 99.6% while terbinafine had89.73% composite score. Similarly reported by H.R.Jerajani et al.17 that means total composite score (pruritus, erythema, vesicle and desquamation) of luliconazole was 92.9% than it was terbinafine 91.2%. In the present study, we found that only a few patients (n=5/79, 6.33%) were reported adverse events during the treatment, out of which n= 2/41, 4.87% of patients were reported adverse reactions from luliconazole while n=3/38, 7.9% from terbinafine. These adverse reactions were very mild i.e. itching, burning and hyperpigmentation and did not require discontinuation of the drugs. A similar study from the other state of India was carried out by VC Laxmi et al.18 in their study they reported four patients in the terbinafine group showed mild contact dermatitis versus none in the luliconazole. Similarly, Jones et al.19 and Watanabe et al.20 reported fewer side effects of 1% application of luliconazole than terbinafine. No application site reactions or systemic events were reported in the other trials.17-23 In contrast to our study, a separate study is carried out by Chandana T et al.24and demonstrates that luliconazole has more adverse effects (20.0%) than terbinafine (16.6%). Conclusion: Adequate treatment of fungal skin lesions with most of the currently used antifungal drugs requires prolonged treatment for complete clearance of the fungal elements which frequently results in noncompliance of the patients; once the clinical features begin to subside. It is possible that a small number of dermatophytes may remain below the detection limit and can survive to some extent in these partially treated lesions and/or surrounding tissues. As a result, the high relapse rate in patients who were previously considered cured is one of the biggest challenges in the treatment of fungal infection. To tackle this, it is desirable for an ideal antifungal drug should have broad-spectrum fungicidal activity at a minimum concentration along with a high mycologic and clinical cure rate with a low incidence of adverse drug reactions even after short-term use. The present study reveals that luliconazole is a safe and effective drug for the treatment of dermatophytosis even in paediatric patients with mild adverse reactions at short term therapy. Acknowledgement: Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Source of Funding: Nil Conflict of Interest: Nil Authors’ Contribution: Dr. Harinkhere Sanjay Kumar (Postgraduate Student)– Principal Investigator            Dr. Arya Raj Kumar (Professor) - Co-Investigator/ Supervisor / Guide            Dr. GargAnubhav (Professor)- Co-Investigator/ Co-Supervisor / Co-Guide            Dr. Ranjan K. P. (Associate Professor)-Co-Investigator/ Co-Supervisor / Co-Guide Dr. Kothari Saroj- Professor and Head Englishhttp://ijcrr.com/abstract.php?article_id=4131http://ijcrr.com/article_html.php?did=4131 Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses 2008; 51: 2–15 Zayas N, Tosti A, Rebell G, Morelli R, Bardazzi F, Bailey H, et al. Autosomal dominant pattern of distal subungual onychomycosis caused by Trichophyton rubrum. J Am Acad Dermatol. 1996 Feb;34(2 Pt 1):302-4 Seeliger, H. P. R. The discovery of Achorionschoenleinii: facts and ‘‘stories.’’ Mykosen 1985; 28:161–182 Weitzman I, Summerbell RC. The dermatophytes. Clin Microbiol Rev. 1995 Apr;8(2):240-59. Borelli C, Korting HC, Bödeker R-H, Neumeister C. Safety and Efficacy of Sertaconazole Nitrate Cream 2% in the Treatment of Tinea Pedis Interdigitalis: A Subgroup Analysis. Cutis; 2010. 85:107-111. Nishiyama Y, Asagi Y, Hiratani T, Yamaguchi H, Yamada N, Osumi M et al. Morphological changes associated with growth inhibition of Trichophyton mentagrophytes by amorolfine. Clin Exp Dermatol. 1992;17 Supp 1:13–17 Nimura K, Niwano Y, Ishizuka S, Fukumoto R. Comparison of in vitro antifungal activities of topical antimycotics launched in 1990s in Japan. Int J Antimicrob Agents. 2001;18:173–178. Dias MF, Bernardes-Filho F, Quaresma-Santos MV, Amorim AG, Schechtman RC, Azulay DR et al. Treatment of superficial mycoses: Review. Part II. A Bras Dermatol. 2013;88:937–944. Khanna D, Bharti S. Luliconazole for the treatment of fungal infections: An evidence-based review. Core Evid. 2014 Sep 24;9:113-24  Phan NQ, Blome C, Fritz F. Assessment of pruritus intensity: a prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471patients with chronic pruritus. Acta DermVenereol 2012; 92:502–7. Venkatesan G., Ranjit Singh A.J.A., Murugesan A.G., C. Janaki C., Gokul Shankar S.Trichophyton rubrum – the predominant etiological agent in human dermatophytoses in Chennai, India. Afr J Microb Res. 2007,5: 009-012. Emmons, C. W. Dermatophytes: natural groupings based on the form of the spores and accessory organs. Arch. Dermatol. Syphilol. 1934; 30:337–362.  Rippon, J. W. The changing epidemiology and emerging patterns of dermatophyte species. Curr. Top. Med. Mycol. 1985; 1:209–234. Gupta A, Daigle D. A critical appraisal of once-daily topical luliconazole for the treatment of superficial fungal infections. Infect Drug Resist. 2016;9:1-6 Ghannoum MA, Long L, Kim HG, Cirino AJ, Miller AR, Mallefet P et al. Efficacy of terbinafine compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis in a guinea pig model. Med Mycol. 2010 May;48(3):491-7 Jerajani H, Janaki C, Kumar S, Phiske M. Comparative assessment of the efficacy and safety of sertaconazole (2%) cream versus terbinafine cream (1%) versus luliconazole (1%) cream in patients with dermatophytoses: a pilot study. Indian J Dermatol. 2013 Jan;58(1):34-8 Lakshmi VC, Bengalorkar GM, Shiva Kumar V. Clinical efficacy of topical terbinafine versus topical luliconazole in treatment of tinea corporis/tinea cruris patients. Br J Pharm Res. 2013;3:1001–1014.  Jones TM, Jarratt MT, Mendez-Moguel I. A randomized, multi-center, double-blind, vehicle-controlled study evaluating the efficacy and safety of luliconazole cream 1% once daily for 7 days in patients aged $12 years with tinea cruris. J Drugs Dermatol. 2014;13:32–38. Watanabe S, Takahashi H, Nishikawa T. A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment fortinea pedis. Mycoses. 2006;49:236–241.   Jarratt M, Jones T, Kempers S. Luliconazole for the treatment of interdigital tinea pedis: a double-blind, vehicle-controlled study. Cutis. 2013;91:203–210.   Selvan A, Girisha G, Vijaybhaskar, Suthakaran R. Comparative evaluation of newer topical anti-fungal agents in the treatment of superficial fungal infections (tinea or dermatophytic) Int Res J Pharm. 2013;4:224–228.  Jones T, Tavakkol A. Safety and tolerability of luliconazole solution 10 percent in patients with moderate to severe distal subungual onychomycosis. Antimicrob Agents Chemother. 2013;57:2684–2689. Chandana T, Saritha CH, Shankaraiah P. Comparison of safety and efficacy of laliconazole and other antifungal agents.  Int. J. Pharma Sci. Res. Vol 5 No 01 Jan 2014

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareClinical Study of Scleral Fixated Posterior Chamber Intraocular Lens Implantation and its Morbidity English2326Neha MaheshwariEnglish B.S. JoshiEnglish V H KarambelkarEnglishEnglish Glaucoma, Intraocular lens, Posterior chamber, Cataract surgery, Retinal detachment, Ab-externo fixation techniqueINTRODUCTION Implantation of intraocular lenses is the standard procedure done in cataract surgery. Ideally, the lens is placed in the capsular bag (Posterior chamber intraocular lenses), which is close to the nodal point of the eye. However, there are instances where it is not possible to achieve in conditions like congenital (e.g., familial or idiopathic ectopia lentis, Marfan syndrome, etc) and secondary weakness of the lens zonules, type of cataract (e.g., traumatic cataracts with lens subluxation, cataracts in pseudoexfoliative syndrome with zonular/capsular dehiscence) or to intraoperative surgical complications (e.g., large breaks in the posterior capsule or posterior capsular rupture during cataract extraction, accidental aspiration of the capsular bag etc), trauma, lens dislocation, surgeons need to employ a technique to fixate an IOL without the support of capsule. Three principal alternatives for fixation are-  1. Scleral suture-fixated posterior chamber intraocular lenses. (SFIOL). 2. Peripheral iris suture-fixated posterior chamber IOLs. 3. Anterior chamber intraocular lenses. (ACIOL). Anterior chamber angle supported lenses are close to the cornea and anterior chamber angle, increasing the risk for bullous keratopathy, glaucoma, and peripheral anterior synechiae.1  In absence of capsular support, SFIOLs have become increasingly popular over the past decade. 2 Also SFIOL is an alternative to patients with complications of implanted ACIOL and those with contraindications to ACIOL and iris or angle-related abnormality.  In 1986, Malbran and co-authors first reported trans-scleral sulcus fixation of posterior chamber lenses in aphakic patients. 3  Intraocular lens placement in the posterior chamber reduces the risk of various complications like bullous keratopathy, damage to anterior chamber angle, pupillary block glaucoma, iris chafing, hyphema, uveitis, and pseudo phacodonesis. 4 The surgical techniques which are explained for trans scleral sutures to fixate a posterior chamber intraocular lens are Ab interno (inside out) and ab externo (outside-in). 5,6  Ab- interno (inside out) technique involves the passage of sutures from the inside of the eye to the outside whereas the Ab-externo (outside-in) technique involves the passage of a suture from the outside of the eye to the inside. In the Ab-externo method, the intraocular lens placement occurs in the ciliary sulcus and the view of the surgical field is never obscured. The risk of vitreous haemorrhage decreases as all the manipulations occur in the iris plane. 7 MATERIALS AND METHODS This prospective study was conducted in Krishna institute of medical sciences Karad from OCTOBER 2018- MAY 2020 for 18 months INCLUSION CRITERIA-    •Patients who underwent scleral fixation of posterior chamber intraocular lens (SFIOL) implantation in the Ophthalmology Department in Krishna hospital, Karad during the study period.  EXCLUSION CRITERIA- •All anterior segment pathology like central corneal opacity, glaucoma, uveitis etc. affecting the visual outcome. •All Posterior segment pathologies affecting visual function like macular degeneration, chorioretinal atrophy etc., and complicating the surgery. •All patients with manifestations of systemic diseases affecting the outcome of surgery. •Patients who did not come for complete 3 month follow up period. METHODOLOGY Patients having a history of eye trauma with capsular bag rupture or complicated cataract surgery causing aphakia and those who completed 3 months follow-up were included in the study.  A standard case proforma was maintained and a detailed clinical history was taken. PREOPERATIVE EVALUATION 1. Uncorrected and best-corrected visual acuity using Snellen’s distance and near visual acuity chart. 2. Slit-lamp biomicroscopic examination- 3. Measurement of IOP in all patients preoperatively. 4. FUNDUS EXAMINATION 5. IOL POWER CALCULATION - using SRK-T formula. 6. B scan and OCT done whenever required. SURGICAL TECHNIQUE All the surgeries were performed by the same surgeon. Anaesthesia and akinesia of globe obtained by peribulbar block with a mixture of 2% xylocaine with adrenaline with 2ml of 0.75 % bupivacaine with the addition of hyaluronidase were used. The skin around the eye is painted with 5% povidone-iodine and the same drops instilled topically. 1. After preparing the patient, a superior conjunctival peritomy from 4 o&#39;clock to 10 o&#39;clock position was created. 2. Partial-thickness triangular scleral flap of 3×2 mm at 4 and 10 o&#39;clock positions created. 3. A 7 mm corneal scleral wound was made and a complete anterior vitrectomy was performed. 4. Anterior chamber and retro pupillary space were filled with viscoelastic substance. 5. Using a straight needle with 10-0 polypropylene suture was passed through one end of the sclera bed, 1 mm posterior to the surgical limbus and parallel to the iris until it was visualized through the pupil. 6. A 28 gauge hollow needle was passed through a 4 o&#39;clock sclera bed was used to retrieve the straight needle, via its barrel. 7. Using a sinskey hook the loop of suture was retrieved through the corneoscleral wound. 8. After cutting the loop of the suture, it was tied to superior and inferior eyelets of the haptic of the IOL. 9. The IOL was placed in the sulcus and sutures were gently pulled to secure the position of the lens. 10. A second 10-0 polypropylene suture is used to take a bite just anterior to the original suture exit point in the scleral bed. The long end of the second polypropylene suture is tied to both its short end and the lens-fixing suture. 11. This was repeated at the other end of the scleral bed. 12. The scleral flap and conjunctival peritomy was closed. Postoperatively patients were treated with topical Moxifloxacin 0.5 % + Dexamethasone 0.1 % eye drops 2 hourly which was gradually tapered. POSTOPERATIVE EVALUATION-All patients were examined on the next day and were followed up after one week, one month and three months of the surgical procedure. RESULTS In the present study, we observed that the majority of the study subjects belonged to the age group of 56 to 65 years (47.76%), followed by 66 to 75 years (20.90%) then 46 to 50 years (14.93%).  . Majority of the study subjects were males (58.21%), while 40.30% subjects were females Right eye was affected among 52.24% study subjects, while the left eye was affected among 47.76% subjects. The majority of the study subjects had preoperative BCVA as indicated in table 1 which was less than 6/60 (41.79%), followed by 6/24 among 38.81% subjects, 6/36 among 14.93% subjects and 6/18 among 4.48% subjects. In table 2, Postoperative BCVA has been indicated which was less than 6/18 (32.84%), followed by 6/24 and 6/60among 20.90% subjects, 6/12 among 14.93% subjects and 6/36 among 10.45% subjects. DISCUSSION In the present study, all the patients (67) were selected for scleral fixation of posterior chamber intraocular lens (SFIOL) implantation. The mean age of the study subjects was57.39 ± 12.67 years. In the kwong et al. study the mean age of the patients was 76.7 years.8 Our study had 39 males and 27 females. The male to female ratio was 1:0.69. Regarding laterality, both eyes were almost equally affected (35 right eyes and 32 left eyes). The most common diagnosis at presentation was post-surgical aphakia (65.67%) followed by the subluxated lens (19.41 %), traumatic subluxated lens (10.45%) and traumatic aphakia (5.98%). No studies have been found that included all the above inclusion criteria for SFIOL implantation. In our study, all the post-surgical aphakia patients had undergone secondary procedures and all the traumatic patients had undergone primary procedures. In Lee et al study there were 30(54.5%) in the primary group and 25(45.5%) in the secondary SFIOL group8.In 39 patients the pre-operative visual acuity was between 6/36 to 6/18 and 28 patients had visual acuity of 6/60 and less. The mean duration of SFIOL implantation was 60 minutes. In Kwong et al. study the mean duration was 65min (SD±24.12 min).7,8,9 The Kh value pre-operative and post-operative was analyzed using the paired t-test and the p-value was significant (P = 0.0008). The analysis of Kv value pre-operatively and post-operative showed significant change and the p-value was significant (P= 0.00001). The mean pre-operative astigmatism was 1.29 ± 1.47, while the mean postoperative astigmatism was 1.76 ± 1.50. The analysis of mean corneal astigmatism pre and post-operative was found to be significant (p=0.00107). Preoperatively, the majority of the cases had WTR astigmatism (43.28%), followed by ATR astigmatism (34.33%), OBL astigmatism (16.42%). Postoperatively we observed that 44.78% cases had WTR astigmatism, 32.84% cases had ATR astigmatism, and 13.43% had OBL astigmatism. The conversion of one type of astigmatism into another type was noted but the average percentage of the various types of corneal astigmatism has not altered much. Postoperatively BCVA after 1 week was improved to6/9 – 6/ 12 among 46.27% cases followed by 6/18- 6/ 36 among 50.75 cases and≤ 6/60 observed among 20.99 % cases. At 12 weeks 74.62 cases had 6/9- 6/12 visual acuity and the remaining had visual acuity between 6/18-6/36 in 20.89% of cases and ≤ 6/60 in 4.48% cases. The improvement in visual acuity after 12 weeks of follow up is due to treatment of associated complications. The immediate post-operative period was uneventful in 17.91% of cases. The immediate postoperative complications were: corneal oedema among 62.69%, followed by striate keratopathy among 11.94%, anterior uveitis among 2.99%, CME and raised IOP among 1.49% cases each.  68.66% had no postoperative complication after 12 weeks. The incidence of CME and ERM at the end of 12 weeks was 13.43% and 1.49% respectively which were treated medically. These cases were associated with vitreous loss either at the initial event with the loss of capsular support or during scleral fixation. Another contributing factor for the development of CME is light-induced retinal injury due to the increased operating time.10 Increased IOP was noted in 6 cases (8.96%) for 1 week and was controlled with antiglaucoma drugs.11 While doing scleral fixation of IOL, transient anterior uveitis was noted in 2 cases (2.99%) which was treated with steroids and topical cycloplegics. 2 cases (2.99%) had developed Retinal detachment 3 months postoperatively due to too posterior placement of suture fixation and underwent RD surgery. None of the patients had major complications like endothelial decompensation, suprachoroidal or vitreous haemorrhage, dislocation of IOL/ IOL tilt or endophthalmitis. CONCLUSION In our study, we have noted that the rate of complications in the late postoperative period (>3 months after surgery) and found that the complication rate was reduced as compared to the early postoperative period. SFIOL to conclude is a safe and effective option in cases of inadequate posterior capsular support due to surgery or trauma, providing better visual rehabilitation with decreasing long term complication rates. Acknowledgement: We acknowledge the contribution of our university and department for the unending support. Conflict of Interest: There is no conflict of Interest  Source of Funding: No Source of Funding Authors Contribution: This is a collaborative work among all authors. Neha Maheshwari   B.S Joshi, V H Karambelkar, performed the statistical analysis, wrote the protocol, and wrote the first draft of the manuscript. Neha Maheshwari managed the literature searches. All the authors read and approved the final manuscript. Englishhttp://ijcrr.com/abstract.php?article_id=4132http://ijcrr.com/article_html.php?did=41321. Lorente R, de Rojas V, de Parga PV, Moreno C, Landaluce ML, Domínguez R, Lorente B. Management of late spontaneous in-the-bag intraocular lens dislocation: retrospective analysis of 45 cases. J Cataract Refract Surg. 2010 Aug 1;36(8):1270-82. 2. Peyman GA. Vitreoretinal surgical techniques. Routledge; 2019 Jul 12. 3. Malbran ES, Malbran E, Negri I. Lens guide suture for transport and fixation in secondary IOL implantation after intracapsular extraction. Int Ophthalmol. 1986 May 1;9(2-3):151-60. 4. Brunin G, Sajjad A, Kim EJ, de Oca IM, Weikert MP, Wang L, Koch DD, Al-Mohtaseb Z. Secondary intraocular lens implantation: complication rates, visual acuity, and refractive outcomes. J Cataract Refract Surg. 2017 Mar 1;43(3):369-76. 5. Can E, Ba?aran MR, Gül A. Scleral fixation of a single-piece multifocal intraocular lens. Eur J Ophthalmol. 2013 Mar;23(2):249-51. 6. Rau R, Santana CR, Martinez AA, Silva AL, Allemann N. Positioning of intraocular lens haptics intentionally implanted in the ciliary sulcus by ultrasound biomicroscopy. Arquivos brasileiros de oftalmologia. 2013 Jun;76(3):147-51. 7. Seki M, Yamamoto S, Abe H, Fukuchi T. Modified ab externo method for introducing 2 polypropylene loops for scleral suture fixation of intraocular lenses. J Cataract Refract Surg. 2013 Sep 1;39(9):1291-6. 8. Kwong YY, Yuen HK, Lam RF, Lee VY, Rao SK, Lam DS. Comparison of outcomes of primary scleral-fixated versus primary anterior chamber intraocular lens implantation in complicated cataract surgeries. Ophth. 2007 Jan 1; 114(1):80-5. 9. Chan TC, Lam JK, Jhanji V, Li EY. Comparison of outcomes of primary anterior chamber versus secondary scleral-fixated intraocular lens implantation in complicated cataract surgeries.      Am. J. Ophthalmol. 2015 Feb 1; 159(2):221-6. 10. Ceballos EM, Parrish II RK, Schiffman JC. The outcome of Baerveldt glaucoma drainage implants for the treatment of uveitic glaucoma. Ophthalm. 2002 Dec 1; 109(12):2256-60. 11. Collins JF, Gaster RN, Krol WF, Colling CL, Kirk GF, Smith TJ, VA Cooperative Cataract Study Group. A comparison of the anterior chamber and posterior chamber intraocular lenses after the vitreous presentation during cataract surgery: the Department of Veterans Affairs Cooperative Cataract Study. Am. J. Ophthalmol.. 2003 Jul 1;136(1):1-9.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcarePotential Antibacterial Activity of Green Synthesized Copper Nanoparticles and its Characterization English2732Keerthika EEnglish Ishwarya KEnglish Jayashree LEnglish Maripandian SEnglish NivethaEnglish Irivichetty Sai ChandanaEnglishIntroduction and Objective: Copper oxide (CuO) nanoparticles are one of the most significant transition metal oxides in the burgeoning area of nanotechnology due to their intriguing features. Because of its simplicity, eco-friendliness, and potential as next-generation antibiotics, its synthesis using green chemistry principles is gaining traction. Cost-effectiveness, lower toxicity, and remarkable broad-spectrum antibacterial activity against a range of bacteria through the generation of reactive oxygen species (ROS) and release of copper ions. Materials and Methods: For CuO Nanoparticles synthesis Copper sulfate was used as starting material and its reduction was carried by Coriander Leaf Extract from Cu2+ to Cu0 The synthesized Cu nanoparticles were characterized by UV-Visible, FTIR and XRD methods. Transmission electron microscopy (TEM) demonstrated particle sizes in the range of 10–15 nm. CuO nanoparticles demonstrated antimicrobial activity against a range of Gram-positive and Gram-negative bacteria, including MRSA. Time kill determination assay was done. Results: According to TEM energy dispersive spectroscopy, the copper to oxygen element ratio is 54.18 per cent to 45.26 per cent. Most resistant human pathogenic strains, including Gram-positive and Gram-negative bacteria, showed significant inhibitory action (p0.0001). With a 31.66 mm zone of inhibition, the maximum effectiveness was recorded against Bacillus cereus. The addition of a sub-MIC concentration [broth dilution technique] of nano CuO reduced all populations to zero by 4 h. Conclusion: Studies of CuO nanoparticles suggest the release of ions may be required for optimum killing English Copper oxide nanoparticle, X-ray diffraction, Transmission electron microscope, methicillin-resistant Staphylococcus aureus (MRSA), broth dilution technique and Fourier transform Infra-red spectroscopyIntroduction: Copper oxide nanomaterials have been given a wide scope of their applications in various fields from the wellbeing and climate area. 1 Additionally, the antimicrobial action of CuO nanomaterial has made them the solid possibility to be utilized as helpful agents.2 as of now, analysts are confronting a significant test in the medical care area to battle drug opposition. In such manner, step by step a few improved blend procedures are building up that incorporates physical, compound and natural processes.3 Anyway, the utilization of vegetables for the union of nanoparticles is extremely restricted. Here, we use Coriander leaf separate for the blend of Cu NP. Coriander (CoriandrumsativumL.) is a flavour crop that has a place with the family Apiaceae (Umbelliferae) is primarily developed from its seeds over time. 4 Constituent of Coriander is phenolic corrosive including caffeic and chlorogenic corrosive. The flavonoids incorporate quercetin, kaempferol, rhamnetin, apigenin and the majority of these mixes are known to hinder free extremists created in the cell when they are gotten through the eating routine.5 Coriander has been accounted for to have numerous pharmacological exercises like cell reinforcement and antimicrobial. Restricted data on the conceivable antimicrobial movement of nano CuO is accessible. CuO is less expensive than silver, effectively blended in with polymers and generally stable as far as both compound and actual properties. Exceptionally ionic nanoparticulate metal oxides, for example, CuO, might be especially significant antimicrobial specialists as they can be set up with amazingly high surface territories and abnormal gem morphologies.6 The points of this examination were to portray truly, what&#39;s more, synthetically nano CuO and to explore this compound concerning its expected antimicrobial applications. Materials and Methods: Material All of the chemicals and reagents used in this experiment were bought from Sisco Research Laboratory in Chennai and were of analytical quality. Coriander leaves were cleaned well and dried in the shade. To make the plant broth solution, combine all of the ingredients in a large mixing bowl. 20 gm dried leaves of coriander was cut into small pieces and washed with distilled water. This was taken in a 250ml beaker with 100ml of distilled water and then boiled the mixture for 20 minutes at 80°C. Synthesis of Cu nanoparticles using Coriander leaf extract: 10 ml of coriander leaf extract was added to 100ml 0f 1mM aqueous copper sulphate solution in a 250ml conical flask. Kept this flask at room temperature overnight and Cu nanoparticles were separated and settle at the bottom of this solution. The Cu nanoparticle thus obtained was purified by repeated centrifugation method at 5000 rpm for 15minute followed by redispersion of the pellet in deionized water. Then the Cu nanoparticles were dried in the oven at 80°C. Physiochemical Characterization of CuNPs: Spectroscopy in the UV-Visible Range Visualization of peaks acquired from a UV-Vis spectral scan from 200 nm to 800 nm in a UV-Visible spectrophotometer was used to examine optical characteristics (Motras Scientific; UV Plus). Infrared Spectroscopy using Fourier Transform The sample was grounded with a KBr pellet and examined on a Perkin Elmer (Model: Spectrum Two) with a spectrum recorded in the 400–4000 cm1 band for the Fourier transform infrared spectroscopy (FTIR) study. Diffraction of X-Rays With Cu-K radiations (= 0.154 nm) in 2 ranges from 20o to 80o, an X-ray diffractometer (XRD, Model: Mini Flex II; Make: Rigaku) was used to assess the crystallite size, structure, and crystallinity of nanoparticles, followed by data analysis in PowderX software. According to the JCPDS (Joint Committee on Powder Diffraction Standards) database and the International Centre for Diffraction Data, the mean size of nanocrystals for the particle was estimated from the diffraction peaks corresponding to the most intense reflections (ICCD). TRANSMISSION ELECTRON MICROSCOPE The size of the produced particles was determined by transmission electron microscopy (TEM) using a 200kV JEOL transmission electron microscope (JEOL Ltd.). The sample was prepared for TEM investigation by pouring 20 litres of CuO nanomaterial solution onto a Cu grid, drying it at room temperature, and then examining it under the microscope at various magnifications. CuONP Biological Screening. In vitro Antimicrobial Activity of CuONPsagainst Multidrug-Resistant Bacterial Strains According to CLSI (Clinical Laboratory Standard Institute) guidelines, the susceptibility of CuONPs to multidrug-resistant bacterial strains was tested using Kirby-disk Bauer&#39;s diffusion and agar well diffusion methods (2009). 24,25,26 The researchers utilised seven Gram-positive (Staphylococcus aureus, Streptococcus mutans, Streptococcus pyogenes, Streptococcus viridans, Staphylococcus epidermidis, Corynebacteriumxerosis, and Bacillus cereus) and four Gram-negative (Escherichia coli, Klebsiella pneumonia, Pseudomonas an Each strain was tested with around 50L of the test sample (concentration of CuONPs 1.25 mg/50L DMSO). Kept for 37 0C. DMSO was used as negative control while 50μL aqueous extract of Coriandrumsativum was used as positive control and 10μg Streptomycin disk for Gram-positive and 10μg Norfloxacin disk for Gram-negative strains were used as standard: positive control. Antibacterial activity was assessed using a zone of inhibition (ZoI) measured after the incubation period against each tested micro-organisms. Time–kill determination To investigate possible antibacterial activity and thus minimise potential toxicity and resistance problems, mixtures of nanoparticles were also tested. CuO at sub-MBC concentrations was used in killing assays against the following strains: S. aureus strains – MRSA and S. aureusOxford (NCTC 6571); S. epidermidisSE-51; E. coli NCTC 9001; P. aeruginosaPAOI; and Proteus spp. All nanoparticles were prepared in phosphate-buffered saline (PBS) with sonication as described above. At time zero, ca. 5×107 CFU/mL of each microorganism was added to the nanoparticle suspension at a dilution of 1 in 80. Incubation was then carried out in a shaking incubator (200rpm at 37 ?C in air for up to 4 h). Inoculated nano particle-free suspensions in PBS were used as negative controls. Growth was assessed by plating serial dilutions of each nanoparticle/bacterial suspension at different time points onto tryptone soya agar plates. Plates were then incubated at 37 ?C in the air with CO2 for 24 h. Statistical Analysis The experiment was repeated three times, and the mean SEM (S.D) was compared to the standard and statistically analysed using graph-paid instant Dataset1.One way ANOVA. RESULTS The Coriander leaves were purchased from the Local vegetable market in Madurai, India. The extract was filtered through Whatman filter no. 1 and then was stored at 5°C and used within a week. The colour of the solution changes from blue to pale yellow and stirred the solution of coriander leaf extract and copper sulphate solution for homogeneous mixing. [figure: 1a,b,c,d,e]                   The synthesized Cu nanoparticles were characterized by pH of the solution, UV-Visible, FTIR, and XRD. pH of solution the pH of the copper sulphate solution was 2.16, when we added coriander leaf extract to this solution, pH changes from 2.16 to 2.64. the pH of coriander leaf extract was 6.78. From this, we confirmed that the capping between Cu and coriander leaf extract was taken place. UV-Visible The reduction of copper sulphate to pure Cu nanoparticles was monitored by using an ultraviolet visible spectrophotometer. UV-Vis spectral analysis was done by using a double beam spectrophotometer 2203 Systronics range of 400-700. The absorption spectrum of pale yellow nanoparticle solution prepared with the proposed method showed a plasmon absorption band with a maximum of 560nm. [figure:2] FTIR FTIR spectra of biosynthesized copper nanoparticles were recorded to identify the capping and efficient stabilization of the metal nanoparticles by biomolecules present in the coriander leaf extract. The FTIR spectrum of synthesized Cu nanoparticles using coriander leaf extract was shown in Figure 3. The band at 3500 cm-1 corresponds to the O-H stretching of alcohols and phenols. The band at 1575 cm-1 corresponds to the N-H bend of primary amines. The peak at 1418 cm-1corresponds to C-Nstretching of the aromatic amino group. The band corresponds to 2670 cm-1 corresponds to the carbonyl group of flavonoids, phenolic acids etc. The band at 3225 cm-1corresponds to C-O linkages of phenol, acid, flavonoids. The band below 600 cm-1 corresponds to copper. Therefore, the synthesized copper nanoparticles were surrounded by proteins and metabolites such as phenolic acid, carboxylic acid, flavonoids. From the analysis of FTIR studies, we confirmed that phenolic compounds have the stronger ability to bind metal indicating that the phenols could form the metal nanoparticles to prevent agglomeration and thereby stabilized the medium. This suggests that the biological molecules could perform dual functions of formation and stabilization of Cu nanoparticles in the aqueous medium.                 XRD XRD pattern of synthesized Cu nanoparticles using Coriander leaf borth extract is shown in Figure 3. The sample demonstrated a high crystallinity level with diffraction angles of 22.74°, 27.55°, 29.63°, and 33.12° [figure: 4] which correspond to the characteristic of face-centered cubic of copper lines indexed at (1111), (2211), (2100) and (2200). The diffraction angle observed at 21.3° which is related to the Coriander leaf extract. The average size of the copper NPs was found to be 13.88nm. The size of copper nanoparticle was found in the range of 21.66nmto 41.65nm. TEM analysis: TEM analysis demonstrated that nano CuO particles exhibited an approximate equi-axes shape with no sharp edges observed (figure: 5). The particle size was determined to be in the range 22.4–94.8 nm. Minimum bactericidal concentration and time-kill determinations Using time-kill assays, populations of Gram-positive (×4 strains) and Gram-negative (×3 strains) organisms tested were reduced by 68% and 65%, respectively, in the presence of 1000µg/mL nano CuO within 2 h. This was increased to 88% (pEnglishhttp://ijcrr.com/abstract.php?article_id=4133http://ijcrr.com/article_html.php?did=4133[1] Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, The bactericidaleffect of silver nanoparticles. Nanotechnology. 2005;16:2346–53. [2] Sondi I, Salopek-Sondi B. Silver nanoparticles as an antimicrobial agent: a case study on E. coli as a model for gram-negative bacteria. J Colloid Interface Sci. 2004;275:177–82. [3] Cioffi N, Torsi L, Ditaranto N, Tantillo G. Copper nanoparticle/polymer composites with antifungal and bacteriostatic properties. Chem Mater. 2005;17:5255–62. [4] Li Z, Lee D, Sheng X, Cohen RE, Rubner MF. Two-level antibacterial coating with both release-killing and contact-killing capabilities. Langmuir. 2006;33:9820–3. [5] Cava RJ. Structural chemistry and the local charge picture of copper oxide superconductors. Science. 1990;247:656–62. [6] Tranquada JM, Sternlieb BJ, Axe JD, Nakamura Y, Uchida S. Evidence for stripe correlations of spins and holes in copper oxide superconductors. Nature.1995;375:561. [7] Kwak K, Kim C. Viscosity and thermal conductivity of copper oxide nanofluid dispersed in ethylene glycol. Korea–Australia Rheol J. 2005;17:35–40. [8] Xu JF,JiW, Shen ZX, Tang SH, Ye XR, Jia DZ. Preparation and characterization of CuO nanocrystals. J Solid State Chem. 1999;147:516–19. [9] Stoimenov PK, Klinger RL, Marchin GL, Klabunde KJ. Metal oxide nanoparticles as bactericidal agents. Langmuir. 2002;18:6679–86. [10] Kawahara K, Tsuruda K, Morishita M, Uhida M. Antibacterial effect of silverzeoliteon oral bacteria under anaerobic conditions. Dent Mater. 2000;16:452–5.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareA Study to Compare the Effect of Electromyography Biofeedback Versus Mime Therapy on Clinical and Electrophysiological Parameters in Subjects with Bell’s Palsy - A Comparative Interventional Study English3338Bhagat P.English Kakkad A.EnglishBackground: Bell’s palsy is the weakness of muscles supplied by the 7th cranial nerve i.e., the facial nerve. It is a lower motor neuron type of disease of the facial nerve. Objectives: To compare the effects of Electromyography Biofeedback (EMG BFB) and Mime Therapy on electrophysiological parameters in subjects with Bell’s palsy. Method: A group of 31 subjects were selected for the study and randomly divided into two groups: Group A and Group B. There were 16 subjects in Group A and 15 subjects in Group B. Group A received EMG BFB (for Frontalis, Nasalis & Mentalis muscle), and group B received Mime Therapy. Pre and post measurements are taken by using the Electromyography (EMG) test (Amplitude of Frontalis, Nasalis & Mentalis muscles), Nerve Conduction Test (Latency & Amplitude of the facial nerve)and, Sunny brook facial grading score. Results: Wilcoxon signed-rank test was done to see the difference within the group and the Mann-Whitney U test was used to see the difference between the groups. The p-value was set at pEnglishBell’s Palsy, Facial Muscle Weakness, Nerve Conduction Studies, Electromyography biofeedback, Mime therapy, Sunnybrook facial grading score.INTRODUCTION Bell’s palsy is an acute, apparently isolated, lower motor neuron facial palsy for which no cause can be found.1 It is a lower motor neuron type of paralysis or weakness of the 7th cranial nerve i.e., facial nerve demonstrated by unilateral peripheral facial muscle paralysis or weakness. It may affect the forehead, face, and neck muscles. Facial palsy may depend on local axonal damage. Within a few days after the infliction of the primary injury, the distal parts of the affected axons degenerate. Significant initial damage normally leaves the sequel with incomplete facial function. Due to immobility, skeletal muscles atrophy very quickly. A reduction in fibre size and diameter appears to be the most striking morphologic finding, together with a simultaneous increase in intramuscular connective tissue and a reduction in capillary density. Facial muscles differ from other skeletal muscles and do not react in the same way during periods without movement. These muscles are relatively slow to degenerate, have small motor units, and are mostly without muscle spindles. Restoration occurs slowly (months), through the growth of new neurons from the area of the injury, or distally through the growth of branches from remaining axons.2Bell’s palsy accounts for half peripheral facial nerve paralysis with an incidence at about 1 in 60 persons. It is more common in people with diabetes. Idiopathic facial paralysis occurs in every decade of life, with a mean age of between 40 and 44 years. It was less common before the age of 15 and after the age of 60 years. The incidence in men and women was similar. Between 6% and 9% of patients had a previous history of facial paralysis. Facial paresis alone occurred in 31%, while the remainder had total unilateral paralysis.3 The Surface Electromyography(SEMG) Biofeedback provides the information necessary for the correction of the movement and supports the process of rehabilitation3.SEMG biofeedback may be used as an adjunct to the retraining exercises in each of the treatment-based categories. Learning facial movements is difficult without feedback. The use of SEMG biofeedback is to provide a visual or auditory representation of facial function at the time of the rehabilitation session.4            Mime therapy is a performance art to improve the symmetry of facial muscle functions and increases the voluntary strength of muscle to help subjects regain functions of their facial muscles. Mime therapy includes stretching exercises, massage, specific facial expression exercises like vowels & consonants, relaxation techniques & active-assisted range of motion exercises.2 The brain reduces abnormal patterns of movement and restores appropriate patterns of facial muscle activity for intended facial actions.5 The primary outcome measure chosen was Sunnybrook facial grading system with 13 items and Electrophysiologically, Electromyography (EMG) test and Nerve conduction test were the objective investigations of facial muscles function most useful in determining the prognosis of a Facial Nerve Lesion. Bell’s palsy is very common at a young age & as it affects the cosmetic part of an individual, it becomes the responsibility of the physiotherapist to provide his/her best effort for recovery in subjects. Nowadays many recent advances are available for treatments of Bell’s palsy e.g., mime therapy, EMG BFB, Taping, etc. along with conventional treatment like electrical stimulation, facial exercises, etc. The systematic review showed the usefulness of these modalities,6 but no single form of treatment seemed to be superior. In the era of evidence-based practice, individually mime therapy & EMG biofeedback both are proven effective but one out of these two treatments, which one is more effective is not currently available in any literature. Therefore, the purpose of the present study was to compare the effectiveness of EMG BFB&Mime therapy on clinical &electrophysiological parameters in Bell’s palsy. MATERIALS AND METHODS Study Design: Comparative Interventional Study Sampling technique:  Purposive Sampling Study Settings & SourceofData: Various Physiotherapy OPDs in Surat. Allocation: Subjects were allocated to Group A and Group B by Simple Random Sampling (chit method) Sample Size: 31 Group A: 16, Group B: 15 Inclusion criteria: Unilateral Bell’s palsy, Acute onset 1-3 weeks, Age group 16-75 years Exclusion criteria: Central facial palsy7, Facial palsy recurrence7, Subject along with surgery for ear & facial nerve palsy. Ethical clearance was taken from Institutional Ethical Committee. The reason for the study was explained and written informed consent and demographic details were obtained from all the subjects. Description of the groups: Group A: Electromyography Biofeedback + Conventional therapy Group B: Mime therapy + Conventional therapy      All the subjects were treated with the session of Conventional therapy for 30 minutes, 6 days per week, and additional treatment of EMG BFB or Mime therapy was given for 30 minutes, 6 days per week.2The procedure was continued for 5 weeks for both groups. Description of the Intervention: Conventional treatment 4 Interrupted Direct Current (I.D.C.) was used with a pulse duration of 100msfor the muscles of the face (Frontalis, Orbicularis oculi, Buccinators, Nasalis, Orbicularis oris, Mentalis. Ninety contractions were given to each muscle in three sessions. Stimulus intensity was adjusted according to the subject’s tolerance at the level which produced a visible muscle contraction without discomfort. Electrical stimulation was given by using Tapsi computerized muscle stimulator, Model no. 535 and serial no.750213. Electromyography Biofeedback (EMG BFB) 6 A ground electrode was placed on the chin or base of the neck. The reference electrode was placed on a 3cm distal from the recording electrode. Active electrode placement accordingly to activate the muscle (Frontalis-1 cm above the eyebrow, Nasalis- posterior end of the lower margin of ala, and Mentalis-1 cm lateral to middle of chin midway between chin lower border & the lip.) Subjects were asked to perform the actions of those muscles. EMG BFB therapy was initiated as soon as the first action potential in the affected muscle was recorded. EMG BFB was given by the Bio Stream MEDICAID machine. Serial No. Bo 71713 with sweep speed of 10 ms/division & Gain or sensitivity of 200uV. Mime therapy 8 It includes: Stretching exercises to relieve muscles involved in synkinesis. Massage for face and neck daily for 10-15 minutes. Facial expression exercises: 5 repetitions. Relaxation technique, which is combined significant asymmetry of facial posture at rest (as for movement control category) with muscle twitching and facial spasm. Outcome measures: Data of all subjects were taken on before the 1st session, at the end of the 15th session, and end of the 30th session. Data were evaluated by the Sunnybrook scale, Electromyograph test, and Nerve conduction test. Amplitude (mV) of Motor Unit Action Potential (MUAP) of facial muscles by Electromyography test: The amplitude of Motor Unit Action Potential (MUAP) was measured from peak to peak of phase. The ground electrode is on the chin or base of the neck. The reference electrode was placed at 3 cm distal to the recording electrode. Recording active electrode was placed accordingly to activate the muscle (Frontalis-1 cm above the eyebrow, Nasalis- posterior end of the lower margin of ala and mentalis-1 cm lateral to middle of chin midway between chin lower border & the lip). Subjects were asked to perform the actions of those muscles.9 The latency (ms) and amplitude of Compound Motor Action Potential (CMAP) of the facial nerve: The latency (ms) of the facial nerve is measured from stimulus artefact to the 1st deflection from the baseline. The normal latency (ms) is below 4.1ms. Amplitude is measured from peak to peak of the negative phase with all the subjects in supine lying. Recording surface electrodes are placed on Nasalis for evaluation of facial nerve. The reference electrode was placed on the bridge of the nose. A ground electrode was placed on the chin or base of the neck. The nerve is stimulated just below the earlobe either anterior or posterior to it.9 Sunny-brook facial grading system score: Subjects were assessed with Sunny-brook facial grading system score. STATISTICAL ANALYSIS                The whole statistical analysis was done by using the SPSS 20.0 version for Microsoft windows. All statistical analysis was calculated using an alpha level of 0.05. The normality of the data was checked by the Shapiro-Wilk test. Means and standard deviations were calculated as a measure of central tendency and measure of dispersion respectively. RESULTS In the present study, 31 subjects with the age group of 16 to 75 years were taken and randomized into 2 groups. Group A (EMG BFB &Conventional treatment) and Group B (Mime therapy &Conventional treatment). Subjects were evaluated before the 1st session and at end of the 30th session. See Table 1 for baseline characteristics of the subject of both groups. Patients in both groups were found with no significant difference in their baseline characteristics. The effects of treatment in Group A on the EMG test, Nerve conduction test and Sunny brook facial grading score were evaluated using Wilcoxon signed-rank test as shown in Table 2. A significant difference was found in all outcome measures except amplitude (mV) in the nerve conduction test suggestive of the effectiveness of SFBFB with conventional treatment. The effects of treatment in Group B on the EMG test, Nerve conduction test and Sunny brook facial grading score were evaluated using Wilcoxon signed-rank test as shown in Table 3. A significant difference was found in all outcome measures except amplitude (mV) in the nerve conduction test suggestive of the effectiveness of Mime therapy with conventional treatment. The effects over time of the interventions on Sunnybrook facial grading score, EMG test, and Nerve conduction test were evaluated using Mann Whitney U test for intergroup analysis and no significant difference was found when compared intergroup improvements as explained in Table 4. DISCUSSION  The study was conducted to compare the effect of EMG BFB and Mime Therapy on patients with acute Bell’s palsy. All the patients had received conventional physiotherapy treatment along with EMG BFB in Group A and Mime therapy in Group B. The duration of electromyography biofeedback is 20 minutes and conventional treatment was 30 minutes. Treatment was given 6 days for 5 weeks. For the comparison of pre and post effects of both the groups&#39; Electromyography test, Nerve conduction test, and Sunnybrook facial grading score. The result of intragroup comparison in Group A (EMG BFB) showed significant improvement in amplitude (mV) of MUAP Frontalis, Nasalis, and Mentalis muscle in EMG test with a significant reduction in latency (ms) of Nerve conduction test and significant improvement in Sunnybrook facial grading score in patients with Bell’s palsy. There is no significant improvement in amplitude (mV) of CMAP in the nerve conduction test. The result of intragroup comparison in Group B (Mime therapy) shows significant improvement in amplitude (mV) of Frontalis, Nasalis and Mentalis muscle in EMG test with a significant reduction in latency (ms) in Nerve conduction test as well as significant improvement Sunnybrook facial grading score on patients with Bell’s palsy. There is no significant improvement in amplitude (mV) of CMAP in the nerve conduction test. The result of the intergroup comparison showed there is no significant difference between EMG BFB and Mime therapy on EMG test, Nerve conduction test, and Sunnybrook facial grading score. The study did not demonstrate statistically significant differences among the two different treatment groups. A systematic review about exercise therapy for Bell’s palsy was published in 2008 with four studies. Meta-analysis was not done because the studies had an opposing combination of characteristics like time of duration of the intervention, treatment type, and outcome measures. The study did not demonstrate clinical or statistical differences among the different treatment groups but improvements were noted in all treatment groups.9                              Similar findings were reported in a previous study of Balliet et al. (1992) conducted a study on combined with EMG facial exercises to increase functional facial movements, including eyelid control, through a comprehensive program as neuromuscular retraining with 7 to 8-month program. Balliet referred to his comprehensive program as neuromuscular facial retraining.10 May et al(1972) reported improvement in 12 of 13 Bell’s palsy patients in only 1 or 2 EMG sessions.11In accordance with a study of Cronin and Steenerson (2003) conducted a study on surface electromyography results revealed improvement in facial symmetry.12 Referred to as EMG biofeedback, its purpose is to bring the normally unconscious control of muscles under conscious control. Decreased activity in hyperactive muscles and increased activity in weak muscles as well as improve coordination of muscle groups.EMG is an important part of the program because it provides immediate feedback to the patient, providing an objective means of measuring movements and outcomes. The facial paralysis, and aberrant regeneration presented before treatment in the treatment group and the success made in normalization of movements and function as a result of treatment support the need for this type of intervention.13 In 2008, the Cochrane Library published a systematic review about physical therapy and Bell’s palsy including six studies with patients who had a whole diagnosis of Bell’s palsy and underwent various types of treatment: faradic stimulation, galvanic current, massage, infrared, acupuncture, and drugs. No statistically significant inter-group differences were found.9     Mistry Gopi et al. (2013) conducted a study on the comparison of the role of Mime therapy vs. conventional therapy on Sunnybrook facial grading system in patients with acute Bell’s palsy. The result showed that Mime therapy improved facial symmetry & functions more than conventional therapy & home exercise in people with acute Bell’s palsy. So, this study supported the use of Mime therapy. Massage done in Mime therapy increases production and creates new growth of connective tissue and collagen in facial muscles and restores facial muscle action. The cost of the treatment is low as along with therapy at a physiotherapy centre, a home program is an integral part of the treatment. So, Mime therapy is also a good choice of treatment for people with Bell’s palsy. Thus, Mime therapy can be used in the treatment of people with acute Bell’s palsy to get improvement in facial asymmetry within a shorter period.14 Statistical analysis for both the groups demonstrated that there is no significant difference in EMG BFB and Mime therapy on the EMG test, Nerve conduction test, and Sunnybrook facial grading score outcome measures between the two groups. LIMITATIONS: The sample size was small. Subjects were not followed up for a longer period. The therapist was not blinded.           FUTURE RECOMMENDATIONS: The same study can be done with larger sample size. A comparative study including different age groups can be done. The same study can be done with sub-acute & chronic Bell’s palsy patients. A future study can be carried out to know the long-term benefits of the intervention. Different outcome measures can be taken. A Control group can be added.          CONCLUSION From this study, one can state that conventional physiotherapy with an EMG biofeedback and Mime therapy has a positive effect on electrophysiological parameters in patients with Bell’s palsy. Hence, both interventions are effective for improving facial muscle functions in patients with Bell’s palsy.  However, both treatments EMG BFB and Mime therapy are equally effective in patients with Bell’s palsy. AUTHOR’S CONTRIBUTION: The first author searched the literature, collected data and wrote the manuscript. The second author reviewed and revised the manuscript as her supervisor. ACKNOWLEDGEMENT We would like to thank the Management, Principal, and Staff members of SPB Physiotherapy College, Surat for allowing us for this research. CONFLICT OF INTEREST: Nil SOURCE OF FUNDING: Nil Englishhttp://ijcrr.com/abstract.php?article_id=4134http://ijcrr.com/article_html.php?did=4134 Golwalla A. Golwalla&#39;s Medicine for Students. Delhi: Jaypee Brothers Medical P; 2017 Sharvani Belle Praveen Kumar et al., Efficacy of mime therapy and conventional therapy versus conventional therapy in improving the facial functions of Bell’s palsy.Int J Sci Res Rev. 2018, 7(1), 427–441 Balliet R, Shinn JB, Bach-y-Rita P. Facial paralysis rehabilitation: retraining selective muscle control. Int Rehab Medicine. 1982 Jan 1;4(2):67-74. Mistry G., Sheth M., Vyas N.Comparison of the effect of mime therapy versus conventional therapy on the sunny brook facial grading system in subjects with acute Bell’s palsy. Int J Med Res Health Sci. 2014 Jan 1;3(1):133-136.                                                             Peitersen E. Bell&#39;s palsy: the spontaneous course of 2,500 peripheral facial nerve palsies of different etiologies. Acta Oto-Laryng. 2002 Jan 1;122(7):4-30. Sittel C, Steinert E. Prognostic value of electromyography in acute peripheral facial nerve palsy. Otol Neur. 2001 Jan 1;22(1):100-4. Ordahan B, Karahan A. Role of low-level laser therapy added to facial expression exercises in subjects with idiopathic facial (Bell’s) palsy. Lasers  Med Sci. 2017 May 1;32(4):931-6. Hauser S, Josephson S. Harrison&#39;s Neurology in Clinical Medicine, 3E. New York: McGraw-Hill Publishing; 2013. Misra D. Clinical Neurophysiology. [Place of publication not identified]: Elsevier India; 2014. Akcan FA, Dundar Y, Uluat A, Korkmaz H, Ozdek A. Clinical prognostic factors in patients with idiopathic peripheral facial nerve paralysis (Bell’s palsy). The European Research Journal. 2017;3(2):170-4. Peitersen E. Bell&#39;s palsy: the spontaneous course of 2,500 peripheral facial nerve palsies of different etiologies. Acta Oto-Laryngologica. 2002 Jan 1;122(7):4-30. GW Cronin, RL Steenerson. The effectiveness of neuromuscular facial retraining combined with electromyography in facial paralysis rehabilitation. Otolaryngology-Head and Neck Surgery 128(4):534-538 Neely JG, Cherian NG, Dickerson CB, Nedzelski JM. Sunnybrook facial grading system: reliability and criteria for grading. The laryngoscope. 2010 May;120(5):1038-1045. Mistry G, Sheth M, Vyas N. Comparison of the effect of mime therapy versus conventional therapy on the sunnybrook facial grading system in patients with acute bell&#39;s palsy. International Journal of Medical Research & Health Sciences. 2014;3(1):133.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareValidated Approach of High-performance Liquid Chromatography Method for Degradation Study of Saxagliptin and Metformin HCl English3948Abhilasha MittalEnglish Manoj ChardeEnglish Imran A SheikhEnglishIntroduction: The study focus on its degradation pattern well know antidiabetic drugs are Saxagliptin and Metformin HCl Aim: The research study aims to validate the high-performance liquid chromatography method for the degradation study of Saxagliptin and Metformin HCl. Method: In support of the determination and to study its degradation pattern in various pharmaceutical dosage forms a novel and simple reverse phase liquid chromatographic method has been established. Saxagliptin and Metformin HCl are well known to use in Type 2 Diabetes. The planned work was performed on Younglin (S.K) isocratic System UV Detector C18 column (150 mm × 4.6 mm). A mixture of Potassium Acetonitrile: Pot. Phosphate Buffer (ph 3.2) in the ratio of 25:75 was used as mobile phase in this method and the method was validated as per ICH guidelines along with flow rate 1.0 ml/min (UV detection at 212 nm) Result: By exposing the drug the Saxagliptin and Metformin HCl to acidic, alkaline, H2 O2 and Neutral degradations forced degradation studies were performed. This method (RP-HPLC) is suitable for kinetic studies as well as the assay of pharmaceutical dosage forms and was found to be robust and specific. Conclusion: In any pharmacopoeia, Saxagliptin is not an official drug. While MET was determined by United States Pharmacopeia (USP), and British Pharmacopoeia (BP) both suggest a non-aqueous titration method using anhydrous formic acid as a solvent and 0.1 M perchloric acid as titrant for the assay of MET. An endpoint is determined potentiometrically. EnglishSaxagliptin, Metformin HCl, RP-HPLC, validation, stability-indicating, pharmacopoeia., USP The study focus on its degradation pattern well know antidiabetic drugs are Saxagliptin and Metformin HClIntroduction The Metformin hydrochloride- biguanide in patients with type 2 diabetes improves glucose tolerance and is a highly recommended drug, especially when compared to other antihyperglycemic drugs. Its chemical name is N, N -Dimethyl imidodicarbonimi dicyandiamide. The recommended dose is 500 mg orally twice daily or 500 to 2000 mg once daily. Lactic acidosis is a rare, but serious, problem that can occur due to the accumulation of metformin. Hemodialysis is recommended to correct the acidosis and to remove accumulated Metformin.1 Saxagliptin competes with a DPP4 inhibitor that reduces the activity of incretin hormones, thereby increasing its concentration in the blood and reducing glucose uptake and glucose-based preparation in patients with type 2 diabetes. The recommended dose is 2.5mg or 5mg orally once daily.2        2. Material and Methods Materials: 2.1 Chemicals and reagents Saxagliptin and Metformin HCl were provided from Merck Laboratories ltd. HPLC grade Potassium Acetonitrile, Pot. Phosphate Buffer was procured from Merck Ltd. Millipore Mili Q plus purification system was used to prepare highly pure water. Commercial Formulation: Saxagliptin and Metformin HCl tablets were available in the market. The tablets were checked and stored properly. 2.2 HPLC instrumentation and conditions Chromatographic conditions Subsequent chromatographic conditions were established by trial and error and maintained consistently throughout the study Chromatographic conditions for proposed method HPLC: Younglin (S.K) isocratic System UV Detector Software:Autochro -3000 Column:4.6 x 150 mm Stationary phase:C18 (Primesil) Particle size packinV: 5 mm Mobile Phase: Acetonitrile: Pot.Phosphate Buffer(ph 3.2 with opa):25: 75 Detection Wavelenth: 212 nm Flow rate:1.0 ml/min Temperature: Ambient Sample size: 20 ml 2.2.1 Standard Sample Preparation Preparation of the Metformin & Saxagliptin Standard & Sample Solution: Standard Solution Preparation: The drug’s standard stock solution was prepared by weighing accurately and transferred 10 mg Metformin and 10mg Saxagliptin working standard into a 10ml & 100ml clean dry volumetric flask respectively. To dissolve it completely about 7ml & 70ml of diluent were added and sonicated and with the same solvent, the volume was made up to the mark. Further pipette out 2ml of Metformin and Saxagliptin into a 10ml volumetric flask and diluted up to the mark with diluents from the above prepared Stock Solution. Sample Solution Preparation: The Sample Stock Solution was prepared by weighing accurately and transferred 936.9 mg of Metformin and Saxagliptin Tablet powder into a 100ml clean dry volumetric flask. 70ml of the diluents was added and sonicated to dissolve it completely and the volume was made up to the mark with the same solvent. Further from the above-prepared Stock                                    Std. Metformin Hcl 1000  mg and 10 mg Saxagliptin  in 100  ml NAOH= 10,000 µgm/ml Metformin Hcl and  100µgm/ml   Saxagliptin stock-001 Take   0.1 ml stock  and make 10 ml with mobile phase   =     1 µg/m/ml Saxagliptin & 100 µgm/ml Metformin Hcl                                                                                                   Take   0.2 ml  stock  and make 10 ml with mobile phase   =    2 µg/ml Saxagliptin  & Metformin Hcl   200 µgm/ml                                                                                                   Take   0.3 ml  stock  and make 10 ml with mobile phase   =      3µm/ml Saxagliptin & Metformin Hcl   300 µgm/ml                                                                                                                                                                                       Take   0.4 ml  stock  and make 40 ml with mobile phase   =     4 µg/ml Saxagliptin & Metformin Hcl   400 µgm/ml                                                                                                   Take   0.5 ml  stock  and make 50 ml with mobile phase   =                      5 µgm/ml Saxagliptin & Metformin Hcl   500 µg/ml               Tab solution Preparation 20 tablets were taken and were triturated to powder weighing Powder wt. =12.00 gms, having average Powder Weight = 1.200   gms. / Tablet  Eq.Wt for 1000 mg= 1000 x1200 / 500 = 2400 mg. 2400 mgs was taken in 100 ml NAOH i.e =   10000 µgm/ml Metformin Hcl and 100 µgm/ml Saxagliptin STOCK –I   (Sonicate 30 min then fitter with 0.45 µm) was taken as Tablet Stock solution     Tablet Assay Take 0.3 ml from tab stock and makeup 10 ml with MP     3+ 300    µgm/ml    for assay  2.3 Forced degradation studies 5, 6 To prove the stability-indicating property of the method the forced degradation studies were performed on Metformin HCl and Saxagliptin. The stress conditions employed for degradation study of Metformin Hcl and Saxagliptin include light exposure, water hydrolysis and oxidation (3 % H2O2), acid hydrolysis (1 N HCl), base hydrolysis (1N NaOH), heat (105°C), Peak purity of the principal peak in the chromatogram of stressed samples of Saxagliptin and Metformin Hcl tablets was checked using PDA detector.   2.4 Method Ruggedness 7 Ruggedness was tested by analyzing six samples from the corresponding combination of one group by a different analyst using a different column, format and date. % RSD for% assay of ruggedness found was 0.10% for Saxagliptin and 0.32% for Metformin Hcl and Overall% RSD found was 0.14% for Saxagliptin and 0.29% for Metformin Hcl as based in Table no. 3 Linearity 8, 11 With the emergence of the analysis method, the mixture of the standard solution of Saxagliptin and Metformin Hcl at concentration concentrations of 0.5123 μg / ml to 11.2299 μg / ml of Saxagliptin and 159.6713 μg / ml to 3500.0690 μg / ml according to the analysis method according to Metformin in the HPLC system. The coefficient (r) of Saxagliptin and Metformin Hcl using the regression equation and 1 / (concentration2) of the equilibrium weight were calculated. The correlation coefficient (r) found was 0.99942 for Saxagliptin and 0.99990 for Metformin HCl. Method Precision 13, 15 From a homogenous mixture of a single batch six samples were prepared as per the test procedure of methodology and analyzed on HPLC system to evaluate the method of precision for the analytical method. The % RSD of six samples found was 0.16% and 0.15% for % assay of Saxagliptin and Metformin Hcl as tabulated in Table no.2 Accuracy 9, 12 For the determination of the accuracy of the method, a recovery study was carried out by analyzing the samples at three different concentrations at 50, 100 and 150%. The percentage of recoveries at three concentrations was calculated. Robustness 10, 14 A robustness study of the method was carried because of the insignificant variations of the technique, such as changes in the composition of the mobile column temperature, altering flow rate, and mobile phase. Results: Tablet assay: The assay results for Saxagliptin and Metformin HCl were found within the specifications. The developed method was validated as per ICH guidelines. Results are shown in Table 1. Forced Degradation Study: In these results of the study the report on the stability-indicating assay of combination Saxagliptin and Metformin HCl by HPLC in presence of degradation products. For analysis of combination, in this method, the isocratic elution method was selected. The reason behind it is, it gave better peak width and baseline separation, which is suitable for routine analysis of combination. In the study as per ICH guidelines, the developed method was validated. The important part of the process of drug product development is the stability testing forms. How the drug quality substance varies with time under influence of various environmental factors such as light, humidity, temperature, and enables recommendations of retest periods, shelf life to be established, storage conditions is stability testing intends to provide evidence. Results are shown in Figures 3-6. Linearity: The calibration curve showed good linearity in the range of 100-500 mg/ml for Metformin HCl and 1-5 mg/ml For Saxagliptin. In the results, a typical calibration curve has the regression equation of y = 59.68x – 3931 and R² = 0.999 for Metformin HCl and y = 190.7x + 22.55 and R² = 0.999 for Saxagliptin. Results are shown in table no. 2 and figure 7 and 8. Precision: The results of system precision for Metformin HCl and Saxagliptin method precision are found within the prescribed limit of ICH guidelines. Results are shown in table 3. Accuracy: For the accuracy study from all the samples, i.e. n=3 for 80 %, n=3 for 100 % and n=3 for 120 %. The results indicated that the mean of recovery for Saxagliptin was 100.08 %, and % RSD was 0.86, similarly, the mean of recovery for Metformin Hcl was 99.99 %, and % RSD was 1.17. As both % RSD values are less than 2 % hence, the reported % recovery by the developed method of the known added amount of analyte in the sample was within the confidence intervals. The results are shown in Tables No 4 and 5. Robustness: Chromatographic small changes influence the conditions such as organic content in pH of buffer in the mobile phase (0.2%), the wavelength of detection (5%), mobile phase (2%), and change in flow rate (10%), various previous research supported to determine the robustness of the method are also in favour of the developed RP-HPLC. The results are shown in table number 6. Repeatability: Here, the average area, standard deviation and % RSD were calculated for two drugs and obtained as 0.5% and 0.5% respectively for Dapagliflozin and Saxagliptin (Table 16, 17). The combination Saxagliptin and Metformin HCl in presence of degradation products by HPLC is the report on the stability-indicating assay. For analysis of combination in this method, the isocratic elution method was selected. The reason, it gave better peak width, baseline separation, which is suitable for routine analysis of combination. As per ICH guidelines, the developed method was validated. The important part of the process of drug product development is stability testing. The important part of the process of drug product development is the stability testing forms. How the drug quality substance varies with time under influence of various environmental factors such as light, humidity, temperature, and enables recommendations of retest periods, shelf life to be established, storage conditions is stability testing intends to provide evidence. The results are shown in table number  7. Conclusion: The procured pure drug of Saxagliptin and Metformin HCl were found to melt in the range of 149-169°C respectively. The drug was found to be freely soluble in Acetonitrile, potassium buffer, Sparingly soluble in water, alcohol. UV absorption of 10µg/ml of Saxagliptin and Metformin HCl methanol was generated and absorbance was taken in the range of 200-400 nm. λmax of saxagliptin and Metformin HCl in acetonitrile was 214nm and 234 nm respectively. It has been observed that using the mobile phase of acetonitrile + pH buffer gave adequate retention time with good peak shape. Assay for % Label claim for %RSD Calculated. The analysis process was repeated five times with tablet formulations. Tablet Assay for % Label claim for % RSD Calculated. To validate the accuracy of the established method the recovery studies were done. To analysed tablet solution, a definite concentration of standard drug (80%,100%, and 120%), to ascertain the resolution and reproducibility of the proposed chromatographic system for estimation of Saxagliptin and Metformin HCl system suitability parameters were studied. Hereby analyzing various replicates standards of Saxagliptin and Metformin HCl, the method was established. To record any intra-day & inter-day variation in the result that concluded respectively all the solution was analyzed thrice. The Robustness of a method is its capability to remain unpretentious by small thoughtful changes in parameters. Small but careful variations in the optimized method parameters were done to assess the robustness of the proposed method. The effect of changes in mobile phase composition and tailing factor of drug peak, wavelength, flow rate, and retention time was studied. The mobile phase composition was changed in proportion to flow rate was varied and wavelength change of optimized chromatographic condition. %RSD for peak area for Metformin HCl was calculated which should be less than 2%. the result was revealed in the analytical method that was determined. %RSD for peak area for Saxagliptin was calculated which should be less than 2%. the result was revealed in the analytical method that was determined. Liquid chromatography is a technique of physical separation in which the components of a liquid mixture are distributed between two immiscible phases; this has provided us with information regarding the degradation part of the drug under study. Acknowledgement: Authors are thankful to Principal NIMS Institute of Pharmacy Jaipur and RSITC Jalgaon for giving me the opportunity to carry out research work successfully. Conflict of interest: None Source of Funding: Research work is self-financed  Author’s contribution:  Complete Englishhttp://ijcrr.com/abstract.php?article_id=4135http://ijcrr.com/article_html.php?did=4135 Thangabalan B, Srisowmya P, ManoharBabu S. Method development and validation for simultaneous estimation of saxagliptin and metformin in tablet dosage form by RP-HPLC method. Int J Pharm Res. 2014;3(4):363-9. Aswini R, Eswarudu MM, Babu PS. A novel RP-HPLC method for simultaneous estimation of dapagliflozin and saxagliptin in the bulk and pharmaceutical dosage form.Int J  Pharm Sci Res. 2018 Dec 1;9(12):5161-7. Nyola N, Jeyalaban G. Simultaneous Estimation of Saxagliptin Hydrochloride And Metformin Hydrochloride In Active Pharmaceutical Ingredient by RP-HPLC. Ame. J. pharm Res  Sci. 2013;4(3):70-7. Chandrika SK, Yoganarasimha RB, Pujitha S, Quantification of Novel Dpp4 Inhibitor-Saxagliptin by Spectrophotometric and Chromatographic Techniques: Brief Review. Int J Curr Res.  2019; 11(05) 3796-3804. Karimulla SK, Vasanth PM, Ramesh T, Ramesh M. Method development and validation of sitagliptin and metformin using reverse phase HPLC method in bulk and tablet dosage form. Der Pharmacia Lettre. 2013;5(5):168-74. Sheikh IA, Chakole RD, Charde MS,  Application of Validated HPLC Method for Degradation Study of Sitagliptin and Metformin HCl, Int J Adv Pharm. 2017; 07(02): 21-24. Sudhir A, Bidkar JS. Sunil H, Dama GY. RP- HPLC Method Development and Validation for Simultaneous Estimation for Metformin and Sitagliptin in Bulk and Tablet Formulation, Int J Chemtech Res.  2018; 11(11): 428-435. Shaikh J, Shaikh A, Mohamad A, Pathan A, Ali K. Validation of stability-indicating high performance liquid chromatographic method for simultaneous determination of assay of Linagliptin and Metformin drugs in the pharmaceuticals tablet formulations using bupropion as a common internal standard. J Int Phar Sci. 2018;5 (1): 21-28. Harshalatha P, Chandrasekhar KB, Chandrasekhar MV. A novel RP-HPLC method for simultaneous determination of Ertugliflozin and Sitagliptin in bulk and tablet dosage form. Int J Res Pharm Sci. 2019;9(3):1042-50. Sultana S, Hossain MS, Islam MS, Rouf AS. Quantitation of Sitagliptin in Drug Product by Validated Reversed-Phase Liquid Chromatographic Technique. Dhaka University J Pharm. Sci. 2018 Jun 24;17(1):123-129. Gundala A, Prasad VK, Koganti B. Application of quality by design approach in RP-HPLC method development for simultaneous estimation of saxagliptin and dapagliflozin in the tablet dosage form. Brazilian J Pharm Sci. 2019;55. Upadhyay NK, Rathore C, Sapra S, Negi P. Novel RP-HPLC method development and validation for the simultaneous estimation of saxagliptin and glimepiride. Int J App Pharm. 2018;10(3):151-156. Donepudi S, Achanta S. Simultaneous Estimation of Saxagliptin and Dapagliflozin in Human Plasma by Validated High-Performance Liquid Chromatography - Ultraviolet Method. Turk J Pharm Sci. 2019 Jun;16(2):227-233. Vetapalem R, Yejella RP, Atmakuri LR. Development and Validation of a Stability Indicating RP-HPLC Method for Simultaneous Estimation of Teneligliptin and Metformin. Turk J Pharm Sci. 2020 Apr;17(2):141-147.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11Healthcare“Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma” English4957Amr Y. ZakariaEnglish Rania M. LabibEnglish Sameh A. AbdelshafiEnglish Asmaa SalamaEnglish Omneya HassanainEnglish Hoda RabeaEnglish Enas El NadiEnglishBackground: Osteosarcoma (OS) is one of the aggressive bone tumours commonly diagnosed in adolescents and young adults. Aim: The study aimed to investigate the effect of 9 single nucleotide polymorphisms (SNPs) in 5 genes on methotrexate (MTX) plasma level and the association between the SNPs and MTX toxicities. Subjects and Methods: One hundred and thirty-three children with OS were enrolled and treated with four weeks of high-dose methotrexate (HDMTX) as neo-adjuvant therapy in a children’s cancer hospital. Blood samples were genotyped for the studied SNPs (MTHFR rs1801133C>T, SLCO1B1 rs11045879C>T, rs4149081 A>G, rs2306283 A>G, ABCC3 rs4793665C>T, rs4148412T>C, rs733392G>A, ABCG2 rs2231142 G>T, and ABCC2 rs717620C>T using TaqMan® RT-PCR assay. Plasma concentrations of MTX were measured. Toxicities were evaluated, besides the studying of survival analysis and tumour necrosis (TN%). Significance was considered at p < 0.004. Results: Older patients experienced an increased risk of delayed MTX elimination at 72-hour [p = 0.00059, OR 1.19, 95% CI (1.09-1.29)]. Moreover, older patients were associated with protection of developing higher grades of enzymatic hepatotoxicity for (ALT) [p = 0.002, OR 0.88, 95% CI (0.8-0.95)] and (AST) [p = 0.001, OR 0.82, 95% CI (0.76-0.89)]. Patients with (CC) genotypegroup of ABCC3 (rs4793665) C>T(14% of the studied population) associated with protective effect against severe nephrotoxicity [p = 0.003, OR 0.31, 95% CI (0.14-0.67)]. Conclusion: The genotyping of ABCC3 (rs4793665 C>T) and age could help in predicting patients with OS at risk of toxicities due to HDMTX. English Osteosarcoma, SNPs, Methotrexate, Toxicity, Genotyping, ABCC3 (rs4793665). Introduction Osteosarcoma is one of the primary aggressive bone tumours most often diagnosed with approximately 70% in children and adolescents. The most frequent primary sites are the distal femur and proximal tibia. It is distinguished by mesenchymal spindle cells that deposit immature osteoid matrix.1The Rizzoli Institute studies outlined a crucial role of MTX, cisplatin, and doxorubicin as the most active chemotherapeutic agents for OS. The study by El-Refaey et al. highlighted the evidence of 3-year disease-free survival rates of 60-70% following the administration of pre-operative multi-agent chemotherapy followed by surgical resection and maintenance chemotherapy.2 The European and American osteosarcoma study group (EURAMOS) protocol is an international randomized study on patients with OS, which consists of HDMTX (12 g/m2) infused over 4-hours per week as neo-adjuvant chemotherapy for four weeks.3 MTX is an antineoplastic agent and is prescribed in various cancer treatment protocols such as acute leukaemia, breast cancer, and OS. MTX competitively inhibits certain folate-dependent enzymes and the biosynthesis of DNA nucleotides such as purines, pyrimidines, and encoded proteins resulting in apoptosis.4 Extracellular MTX is transported to the cell by various pathways, primarily through active transport mediated by reduced folate carriers. Passive diffusion adds to the transfer of MTX by cellular inflow. The majority of MTX is eliminated by renal excretion and less than 20% undergoes biliary secretion. MTX is transmitted intracellularly by the solute carrier organic anion transporters family member 1B1 (SLCO1B1).5 On the other hand, ABC genes that encode p-glycoprotein are responsible for the efflux of MTX out of the cell, such as human multidrug resistance-related protein 2 (MRP 2), encoded by ABC subfamily C member2 (ABCC2).6Methylene-tetrahydrofolate Reductase (MTHFR) 677C>T rs1801133 is located at the coding region of the gene and may affect its phenotype. Several studies thus far have linked this SNP with toxicity and clinical outcome.7The useful PKs biomarker is the beta elimination half-life in the prediction of delayed elimination when extended.8 Substantially, HDMTX is included in many protocol treatments. HDMTX has a narrow therapeutic index. It can cause significant toxicities such as haematological toxicity, hepatotoxicity, and nephrotoxicity. Acute kidney injury (AKI) represents 2-12% of patients. Nephrotoxicity may be due to the MTX crystals in the lumen of the renal tubules, causing irreversible tubular toxicity. AKI and other toxicities of HDMTX can lead to significant treatment delaying, a decrease in renal function, and morbidity.9 Age, gender, and inter-individual genetic variations may be associated with a decrease in the effectiveness of drug therapy, or side effects, or toxicity, or treatment failure.10 According to the American Society of Health-System Pharmacists (ASHP), ? Pharmacogenetics (PGs) investigates the effect of genomic variations on drug responses. PGs testing can improve drug response that may include sub-optimal clinical outcomes, decreased cost of treatment, better medication adherence, more appropriate selection of therapeutic agents, decreased length of treatment, and enhanced patient safety. ? SNPs are the leading cause of genetic variations and account for approximately 90% of the variation in the human genome. It may influence the role or expression of the gene, the inter-individual differences in pharmacokinetics (PKs), and pharmacodynamics (PDs) parameters.11Based on data available from the Pharmacogenomics Knowledge database (www.pharmagkb.com), we selected SNPs with a reported minor allele frequency higher than 10% (MAF ≥0.1) in the Caucasian (Egyptian populations). Each SNP of these genes is predicted to affect therapeutic limitation and clinical decisions, including ethnic PKs and PDs gene variations that affect phenotype.12 The current study aimed to determine the allelic frequencies of 9 SNPs in 5 genes (MTHFR, SLCO1B1, ABCC3, ABCG2, and ABCC2) involved in the MTX pathway in the children with OS. Our study investigated the role of PGs variations on MTX elimination, toxicities, survival, and tumour necrosis (TN%). Hopefully, this will help us in the future to build models that accurately predict strategies for individual patients and use this knowledge to personalize treatment plans. Patients/Methods 2.1. Design and participants A retrospective cohort study included 133 patients diagnosed with a localized non-metastatic OS of the extremity treated based on the EURAMOS protocol at the hospital between 2013 and 2018 in Cairo, Egypt. The study was approved by the Institutional Review Board (IRB) with serial number 1112018 (25 June 2018). All patients and their parents or legal guardians have signed written informed consent. The samples and data were collected and documented between April 2018 to Jan 2019. Patients were included if they fit the following eligibility criteria. Patient inclusion criteria       Newly diagnosed non-metastatic localized resectable disease, primary OS, histological evidence of high-grade OS of an extremity (femur, tibia, humerus, fibula, radius, and ulna), age £ 18 years at the date of the diagnostic biopsy, started chemotherapy within 30 days of diagnostic biopsy, and adequate bone marrow function; neutrophils count > 1.5 x 109/L (or WBC > 3 x 109/L if neutrophils were not available) and platelet count > 100 x 109/L., renal function (glomerular filtration rate ≥70 ml/min/1.73 m2), and liver function (total bilirubin ≤1.5 × upper limit of normal (ULN)). Patient exclusion criteria       Any previous treatment for OS and any medical history of chemotherapy, juxtacortical (periosteal, parosteal) OS, unresectable primary disease, or metastatic, or both, and if patients had been administered any drug before MTX clinical protocol that can affect MTX level that would be recorded. Clinical protocol All patients were treated with HDMTX (12000 mg/m2 I.V over 4-hours infusion), administered at weeks 4, 5, 9, and 10 as per protocol. The leucovorin rescue (LR) of 15 mg/m2/q 6-hours started 24-hours after the initiation of the infusion of HDMTX.13 The patients’ data were collected from Cerner (electronic medical records) using (RED-Capâ), a web-based data collection tool. Genotyping Blood samples (5ml) in EDTA vacutainers were collected for genotyping. Genomic DNA was extracted using the Gene-JET™ kits TaqMan®- Thermo- fisher scientific Baltics UAB V, Lithuania. DNA concentrations were detected using Nano-Quant Infinite M200 PRO (Tecan Group Ltd., Switzerland). Genotyping was carried out using Quant-Studio 12 K Flex Real-Time PCR System Life Technologies Ltd (Paisley PA4 9RF, UK). The predesigned and drug-metabolizing enzymes (DME) studied genes SNPs were processed according to (Thermo- fisher scientific Baltics protocol). The volumes of plate wells didn’t exceed 10-μL for the cycling system. Life Technologies software was adapted for allele discrimination analysis.12 Plasma level analysis of MTX The analyses of MTX levels were carried out post-24-hours infusion initiation time, and every 24-hours, until the MTX level was ≤0.2 μMol/L.14 This was measured by the enzyme multiple immunoassay techniques (EMIT® MTX 2011), supplied with Siemens Healthcare Diagnostics Inc., SYVA®, USA.13 Outcome analysis TN% followed preoperative chemotherapy was histopathological determined. All patients were assessed for HDMTX toxicities and were graded and recorded according to the common terminology criteria for adverse events version 5 (CTCAE v5.0). 5-year overall survival (O.S) and event-free survival (EFS) were analyzed. Statistics The patients were divided into two groups according to genotyping results: group 1 was “homozygous wild”, and group 2 included patients with at least one variant allele “homozygous variant and heterozygous”. Patients` levels of MTX  at 72-hour were categorized  to "good elimination" (72-hour 90% was considered to be good responders.16  Cumulative logit link function for ordinal outcomes was used to examine the relationship between SNPs and toxicities to determine the significance of the selected variables and to estimate effect sizes. 5-years O.S and EFS were estimated using Kaplan – Meier. The log-rank test analyzed the study differences in the estimates of endpoint events over time concerning the SNPs investigated. Hazard ratios and 95 % confidence intervals (CIs) were calculated by Cox proportional hazards regression model for univariate and multivariate analyses to identify independent predictors of O.S and EFS (both SNPs and demographic variables). Quantitative variables were summarized using the range, mean, and standard deviation. The frequency and percentage were used for qualitative variables.The analysis was done using R for statistical computing R version 3.6.1.The significance levels were adjusted using the Bonferroni method. The adjusted significance level was 0.0045. Significance was considered at p < 0.004. Results Patients’ demographics            One hundred and thirty-three patients were eligible and included in this study. The main characteristics of the patients were included in (Table 1). Genotyping The results of genotyping and allelic frequencies are listed in (Table 2). The minor allele frequency (MAF) for MTHFR (rs1801133) C>T, SLCO1B1 (rs4149081) A>G, ABCG2 (rs2231142) G> T, ABCC2 (rs717620) C>T, and ABCC3 (rs4148412) T> C were (0.29, 0.49, 0.27, 0.11, and 0.42, respectively). While for SLCO1B1 (rs11045879) C>T, SLCO1B1 (rs2306283) A>G, ABCC3 (rs4793665) C>T, and ABCC3 (rs733392) G>A, the variant allele was more predominant with an allelic frequency of (0.63, 0.53, 0.60, and 0.85, respectively). *Predominant variant alleles, HW: Homozygous wild genotype; HT: Heterozygous genotype; HV: Homozygous variant genotype., SNPs: Single nucleotide polymorphisms, rs: reference SNP number, N: Number of patients, A: Adenine, G: Guanine, C: Cytosine, T: Thymine, MTHFR: Methylene-tetrahydrofolate reductase, SLCO1B1: Solute Carrier Organic Anion Transporter Family Member 1B1, ABCG2: ATP Binding Cassette Subfamily G Member 2, ABCC2: ATP Binding Cassette Subfamily C Member 2, ABCC3: ATP Binding Cassette Subfamily C Member 3. 4.3.  Genotypes-MTX level analysis  Association between the two patients’ groups of each gene SNP and delayed MTX pattern at 72-hour MTX levels is illustrated in (Table 3). Only age was significantly associated with delayed elimination at 72-hour. A one-year increase in patients&#39; age was associated with a 19% increase in the risk of MTX delayed excretion [p = 0.00059, OR 1.19, 95% CI (1.09-1.29)]. *Significant (P ≤ 0.0045), Exp(B)=Estimated Odds Ratio (OR), CI: The confidence interval, (ref): Reference group, SNPs: Single nucleotide polymorphisms, rs: reference SNP number, MTHFR: Methylene-tetrahydrofolate reductase, SLCO1B1: Solute Carrier Organic Anion Transporter Family Member 1B1, ABCG2: ATP Binding Cassette Subfamily G Member 2, ABCC2: ATP Binding Cassette Subfamily C Member 2, ABCC3: ATP Binding Cassette Subfamily C Member 3.   4.4.  Genotypes-toxicity analysis Older patients were associated with protection of developing higher grades of enzymatic hepatotoxicity for (ALT) [p = 0.002, OR 0.88, 95% CI (0.8-0.95)] and (AST) [p = 0.001, OR 0.82, 95% CI (0.76-0.89)]. Patients with (CC) genotypegroup of ABCC3 (rs4793665) C>T(14% of the studied population) associated with protective effect against severe nephrotoxicity [p = 0.003, OR 0.31, 95% CI (0.14-0.67)]. Association between the two patients’ groups of each gene SNP, age, gender, and different severe toxicities after four HDMTX cycles is illustrated in (Table 4). *Significant (P ≤ 0.0045), Exp (B): Estimated Odds Ratio (OR), CI: The confidence interval, ALT: alanine transaminase, AST: aspartate aminotransferase, (ref): Reference group, SNPs: Single nucleotide polymorphisms, rs: reference SNP number, MTHFR: Methylene-tetrahydrofolate reductase, SLCO1B1: Solute Carrier Organic Anion Transporter Family Member 1B1, ABCG2: ATP Binding Cassette Subfamily G Member 2, ABCC2: ATP Binding Cassette Subfamily C Member 2, ABCC3: ATP Binding Cassette Subfamily C Member 3. 4.5.  Genotypes-outcome analysis The SNPs had not been significantly associated with TN% or O.S and EFS. The survival analysis for ABCC3 (rs4793665) C>T is illustrated in (Figures 1a and1b). Discussion This study examined the emerging role of the pharmacogenetic markers in children with OS to minimize inter-individual variations in chemotherapy such as HDMTX. The objectives of many studies are to design prognostic tools for protection against any potential toxicity resulting in treatment failure, prolongation of hospitalization, and decrease in survival. It was achieved by studying the relation between PGs involving gene SNPs, drug PKs, and PDs. The problem here, many studies had divergent, conflicting findings and a lack of reproducibility, a small number of homogeneous ethnicities, variations in ethnic groups, differences in treatment protocols, varied assessment of toxicity criteria, and clinical outcomes.17 The present study offered essential findings on a retrospective cohort of patients larger than published in prior similar studies. It provided an in-depth analysis of a homogeneous Egyptian ethnicity with the same pre-therapy conditions. They had been treated with the same protocol, reliable, and well-recorded data using the Bonferroni correction method. Toxicity criteria were available/used, survival, and TN% analyses were performed. The most important clinically relevant finding was the reliability of the MTX terminal elimination pattern at 72-hour. The relationship is based on the studies of Imanishi and Trevino et al. on HDMTX in pediatric acute lymphoblastic leukaemia (ALL).8 Therefore, our study relied on an objective and quantifiable marker that was cut off the 72-hour MTX level. Regarding the allelic frequency determination, the significant finding was that the variant allele was more predominant with an allelic frequency of SLCO1B1 (rs11045879) C>T, SLCO1B1 (rs2306283) A>G, ABCC3(rs4793665) C>T, and ABCC3 (rs733392) G>A in Egyptian children with OS. Recent developments in the field of PGs have led to a renewed interest in the polymorphic effect of transporter and metabolism genes on PKs and PDs of MTX. In the current study, a one-year increase in age was associated with a 19% increased risk of MTX delayed elimination pattern at 72-hour. So, older age children were considered poor eliminators of HDMTX in the studied sample. The interpretation of our results may be the low volume of distribution of MTX. The young children have high body water content leading to more MTX elimination than elder children. These results match those observed in earlier studies.18, 19The study of Csordas et al. reported the significant association between high MTX levels in children aged more than 14 years because the metabolism resembles those of adult patients. The younger children were less likely to have delayed elimination due to their physiology.18 The findings of the present study further support the idea of different genotypes did not have a significant association with MTX level as consistent with prior studies.13, 18 Prior studies demonstrated that the risk factors related to the appearance of certain types of toxicities after HDMTX administration. These factors may be due to higher MTX levels after multiple HDMTX cycles or other factors. The previous studies offered contradictory findings of several factors that participate in this association.19-21 The high MTX level wouldn&#39;t predict the appearance- a specific type of toxicity except for nephrotoxicity after multiple HDMTX cycles, described by Tsurusawa et al.22 Mandal et al. revealed that MTX levels didn&#39;t associate with toxicity. He explained that gender, body mass index, and the pre-cycles ANC made that association. Besides, basic serum creatinine was the predictor of toxicity.20 The study of Vaishnavi et al. in low and middle–income countries at a single centre in (Chandigarh, India) recommended that the safe give full HDMTX to ALL patients with extended hydration, additional doses of LR, monitoring of serum creatinine, and pH without therapeutic drug monitoring (TDM) of MTX.23 Herein, older children have significant protection against the risk of severe elevation in liver enzymes, consistent with Holmboe et al.24 The increase in (ALT) and (AST) values might be temporary and reversible, which may not result in chronic liver disease following administration of HDMTX.25 Our study&#39;s recommendations are to translate our findings to patients&#39; bedsides as preventive measures. AST and ALT levels should be closely monitored before and during MTX cycles. Concurrent hepatic inflammation or dysfunction exacerbated by HDMTX doses should be managed, particularly in younger children. As far as ABCC3 is located in the gall bladder, and kidney. The expression of ABCC3 mRNA is associated with drug resistance. Its biological function is organic anion excretion like MTX and bile.26 Children in group 1 having ABCC3 (rs4793665) (CC) genotype (14% of the tested population) were associated with protection against the risk of severe nephrotoxicity even after adjusting for age. The findings were inconsistent with prior studies.6, 12The study results of Hegyi et al. demonstrated that the presence of at least one variant allele T in patients with ABCC3 (rs4793665) causes higher MTX concentrations than wild-type allele C.6 Consequently, our findings explain children with allele C may cause protection against impaired excretion of MTX, 7-hydroxy-MTX, and inactive 7-hydroxy-MTX, and 4-amino-4-deoxy-N-methylpteroic acid (DAMPA). The high-risk patients who suffered from severe nephrotoxicity had involved in the solubilities of HDMTX metabolites in urine may reach ten folds lower than MTX. As a consequence, it may cause renal tubules obstruction, and extended contact of MTX with the renal tubular epithelial tissue lining exposes it to direct toxic AKI. Englishhttp://ijcrr.com/abstract.php?article_id=4136http://ijcrr.com/article_html.php?did=41361. Durfee, R.A., M. Mohammed, And H.H. Luu. Review Of Osteosarcoma And Current Management. Rheumatol Ther, 2016. 3(2): P. 221-243. 2. El-Refaey, O.M. Intensive Chemotherapy For Resectable High-Grade Osteosarcoma Of The Extremities. Cu Theses, 2016. 3. Tsuda, Y., Et Al. The Outcomes And Prognostic Factors In Patients With Osteosarcoma According To Age: A Japanese Nationwide Study With Focusing On The Age Differences. BMC Cancer, 2018. 18(1):1-7. 4. LuengoA., D.Y. Gui, M.G. Vander Heiden.Targeting Metabolism For Cancer Therapy. Cell Chem. Biol., 2017. 24(9):1161-1180. 5. Lui G. A Pharmacokinetic And Pharmacogenetic Analysis Of Osteosarcoma Patients Treated With High?Dose Methotrexate: Data From The OS2006/Sarcoma?09 Trial. J. Clin. Pharmacol, 2018. 58(12):1541-1549. 6. Hegyi, M. Pharmacogenetic Analysis Of High-Dose Methotrexate Treatment In Children With Osteosarcoma. Oncotarget, 2017. 8(6):9388. 7. Giletti AP. Esperon.Genetic Markers In Methotrexate Treatments. Pharmacogenomics J., 2018. 18(6): P. 689-703. 8. Treviño LR. Germline Genetic Variation In An Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics And Clinical Effects. J. Clin. Oncol., 2009. 27(35):5972. 9. HowardS.C.Preventing And Managing Toxicities Of High-Dose Methotrexate. The Oncologist, 2016. 21(12):1471-1482. 10. KalyanpadY. Methotrexate A Double-Edged Sword–Effect Of Methotrexate In Patients Of Psoriasis Due To Medication Errors. Int J Cur Res Rev, 2017. 9(20): P. 10. 11. Jiang, X.-L. Clinical Pharmacokinetics And Pharmacodynamics Of Clopidogrel. Clin. Pharmacokinet., 2015. 54(2): 147-166. 12. De ROTTE, M.C. ABCB1 And ABCC3 Gene Polymorphisms Are Associated With First-Year Response To Methotrexate In Juvenile Idiopathic Arthritis. J. Rheumatol., 2012. 39(10):2032-2040. 13. El Mesallamy, H.O.High-Dose Methotrexate In Egyptian Pediatric Acute Lymphoblastic Leukemia: The Impact Of ABCG2 C421A Genetic Polymorphism On Plasma Levels, What Is Next? J. Cancer Res. Clin. Oncol., 2014. 140(8):1359-1365. 14. Howard SC. Preventing And Managing Toxicities Of High-Dose Methotrexate. The Oncologist, 2016. 21(12):1471. 15. Martinez D. Endogenous Metabolites?Mediated Communication Between OAT1/OAT3 And OATP1B1 May Explain The Association Between SLCO1B1 Snps And Methotrexate Toxicity. Clin. Pharmacol. Ther., 2018. 104(4):687-698. 16. Hattinger CM. Pharmacogenomics Of Genes Involved In Antifolate Drug Response And Toxicity In Osteosarcoma. Expert Opinion On Expert Opin. Drug Metab. Toxicol., 2017. 13(3):245-257. 17. Lopez-Lopez E.Pharmacogenetics Of Childhood Acute Lymphoblastic Leukemia. Pharmacogenomics, 2014. 15(10):1383-1398. 18. Csordas, K. Comparison Of Pharmacokinetics And Toxicity After High-Dose Methotrexate Treatments In Children With Acute Lymphoblastic Leukemia. Anti-Cancer Drugs, 2013. 24(2):189-197. 19. Young EP. Risk Factors Associated With Delayed Methotrexate Clearance And Increased Toxicity In Pediatric Patients With Osteosarcoma. Pediatr. Blood Cancer, 2020. 67(4): E28123. 20. Mandal P. Adverse Effects With Intravenous Methotrexate In Children With Acute Lymphoblastic Leukemia/Lymphoma: A Retrospective Study. Indian J Hematol Blood Transfus, 2020:1-7. 21. LiX. Identifying Risk Factors For High-Dose Methotrexate-Induced Toxicities In Children With Acute Lymphoblastic Leukemia. Cancer Manag. Res., 2019. 11: 6265. 22. TsurusawaM. Statistical Analysis Of Relation Between Plasma Methotrexate Concentration And Toxicity In High?Dose Methotrexate Therapy Of Childhood Nonhodgkin Lymphoma. Pediatr. Blood Cancer, 2015. 62(2):279-284. 23. Vaishnavi K. Improving The Safety Of High?Dose Methotrexate For Children With Hematologic Cancers In Settings Without Access To MTX Levels Using Extended Hydration And Additional Leucovorin. Pediatr. Blood Cancer, 2018. 65(12): E27241. 24. HolmboeL. High Dose Methotrexate Chemotherapy: Pharmacokinetics, Folate And Toxicity In Osteosarcoma Patients. Br. J. Clin. Pharmacol., 2012. 73(1): P. 106-114. 25. HowardS.C. Preventing And Managing Toxicities Of High-Dose Methotrexate. The Oncologist. 2016; 20(10) 0160-0164. 26. Liu, S. Predictive Potential Of ABCB1, ABCC3, And GSTP1 Gene Polymorphisms On Osteosarcoma Survival After Chemotherapy. Tumour Biol. 2014. 35(10): 9897-9904. 27. PerazellaM.A.,G.W. Moeckel. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareTolerance and Remediation Potential of Water Microbes against Nitrate English5864Thakur PreetiEnglish Gauba PammiEnglishIntroduction: Nitrate is the major concern of groundwater. High concentration arises due to the massive application of chemical fertilizers. It causes various issues Blue Baby Syndrome, respiratory problems etc. Conventional methods are available to remove nitrate, but they can sequester the nitrate and not treat it. Bioremediation is a low-cost technique and is efficient in nitrate removal. Objective: Isolation and identification of nitrate-reducing microbes from the polluted site of Yamuna river. Methods: This paper focuses on microbe’s isolationusingBioremediation technique and their identification through Molecular and Biochemical tests. Result: 4 microbes were found to have the potential for remediating nitrate. Microbes were inoculated in nitrate broth and incubated (37?C) under both aerobic and anaerobic conditions. Phenotypical and molecular characterization was done. The consensus sequence was submitted in GenBank and accession numbers were obtained.These were Enterobacteraerogenes (MN252552), Lelliotiaamnigena (MN647560), E. coli K12 (MN754025) and Klebsiella oxytoca (MT457847) respectively. After incubation, these strains showed 48.4%, 34.1%, 42.90% and 33.66% of nitrate remediation under anaerobic conditions while almost negligible under aerobic. Further, these microbes were inoculated in broth containing 1500mg/l nitrate equivalent to the maximum reported nitrate in Yamuna River. E. coli and Enterobacter aerogenes remediated 44% and 46% of 1500mg/l nitrate respectively. Conclusion: These two microbes were found to have moderate potential to remediate nitrate (1500mg/l) which brings novelty to this study. A further detailed study on using microbial consortium to enhance the capability of nitrate remediation will be useful. English Nitrate, Fertilizers, Blue Baby Syndrome, Mutation, Bioremediation, ConsortiumIntroduction Nitrogen is one of the essential nutrients required by plants for their physiological activity, but its availability is limited.1 Plants uptake nitrogen from the soil in the form of nitrate (NO3-) and ammonium ion (NH4+).2 Therefore, chemical fertilizers (nitrogenous fertilizers) are required to boost the fertility of soil 3 and its sufficient amount needed to grow food for the increasing human population.4The use of chemical fertilizers has increased by 80% from 1960 to 2000.5 This overuse of nitrogenous fertilizers has a hazardous effect on the nitrogen cycle, and this also has degraded water quality around the world.6 Ammonium nitrate, ammonium sulfate and urea are the commonly used nitrogenous fertilizers. Ammonium (NH4+) is a positively charged ion that is quickly absorbed by soil and with the help of soil microflora, converts ammonia into nitrate (nitrification).7 Nitrate (NO3-) is a negatively charged ion and its highly soluble property makes it mobile as it easily mixes with groundwater.8                                 There are various detrimental effects of nitrate load in drinking water like- Methemoglobinemia in infants commonly known as Blue Baby Syndrome7, Non-Hodgkin Lymphoma,9 respiratory problems, birth defects, tumour in children10, genetic mutation etc. Besides these, the presence of nitrogenous compounds in water leads to eutrophication which is an anaerobic condition responsible for the death of aquatic animals and plants. In wake of these problems, World Health Organization (WHO) set a maximum limit of nitrate in public drinking water as 50mg/l nitrate or 11.3mg/l as nitrate-nitrogen.11The permissible limit of nitrate is 50mg/l for drinking water and no relaxation for the maximum limit. The maximum reported concentration of nitrate in groundwater, Delhi is 1500mg/l.12 Various conventional technologies available to remove nitrate are ion exchange resins, electrodialysis, distillation and reverse osmosis.13 These can remove nitrate, but they produce secondary wastes. Thus, the worthwhile alternative for the denitrification process lies in bioremediation as it is cost-effective and safe.14          Several denitrifying microbes have been reported to remediate nitrates such as E. coli, Enterobacter aerogenes, Shigella sonnei, Klebsiella pneumonia and Enterobacter amnigenusetc. These all belong to the Enterobacteriaceae family which are Gram-negative and rod-shaped(bacilli). According to the reported data mostly nitrate-reducing microbes are bacilli in nature.15E.coli and Enterobacter amnigenus16have the potential to remediate nitrate. The current study aims to isolate and identify such microbes from the Okhla barrage which is one of the most polluted sites of the Yamuna river.17 Materials and Methods Water quality assessment The physical parameters were visually analysed while chemical parameters were analysed by using a water testing kit (CPCB water testing kit) to examine the water quality of the Yamuna river. Physical parameters checked were colour, odour, turbidity, and pH, and chemical parameters evaluated were Alkalinity, Hardness, TDS, Chloride, nitrates, phosphates, ammonia, etc. Chemicals:  Potassium Nitrate (96% used for nitrate standard) and sulphuric acid (95%) from Qualigens. Salicylic acid (99%) and Nitrate broth from CDH and Himedia respectively. Nutrient broth from CDH. Pure water used was from the Milli Q Biocel unit (Millipore SAS, Malsheim, France).  Nitrate broth containing Peptone-5g, Beef extract-3g, Potassium nitrate-1g/l, pH(7.0). Nutrient broth containing the following: Peptic digest of animal tissue-5g, Beef extract-1.50g, Yeast extract-1.50g, NaCl-5g/l, pH(7.4). Collection and isolation of bacterial species Water samples were collected from the polluted site of Okhla barrage reported as one of the most polluted sites of Yamuna River (CPCB 2017)18 (Table I). Water samples were serially diluted and transferred to nutrient agar containing 500mg/l nitrate and incubated at 37°C for 24hrs. After incubation, bacterial colonies were picked up and then sub-cultured for pure culture isolation. Standard graph for nitrate  3.6g of KNO3 dried at 105°C for 24hrs. It was then weighed and dissolved in 500ml of deionized water and labelled as a 1000mg/L nitrate-nitrogen solution. Nitrate-nitrogen into nitrate and nitrate into nitrate-nitrogen vice versa calculations were done using the formula: Nitrate = Nitrate-nitrogen ×4.43                                    Nitrate-nitrogen= Nitrate ×0.226 Isolation of bacteria and estimating its nitrate remediation potential Four different isolates showed tolerance up to 500mg/l nitrate concentration. These isolates were further checked for their nitrate remediation potential.19 Each isolate was inoculated (4% inoculum) in Nitrate broth and incubated for 72hrs (3 days) at 120rpm under both aerobic and anaerobic conditions. The culture was centrifuged at 8609RCF (Relative Centrifugal Force) for 10mins.20 40µl supernatants were taken and 200µl salicylic acid (5% salicylic acid in sulphuric acid) was added to it. The mixture was vortexed and incubated in dark for 10mins. The reaction was stopped by the addition of 2ml NaOH (4N NaOH). The absorbance was taken at 420nm after 20 mins of incubation.21 The degree of remediation of nitrate was calculated by using the formula: Where X0 is the initial amount of nitrate,   X1 is the amount of nitrate after remediation(72hrs). The final results are calculated with the respect to control samples. (nitrate broth without microorganisms).                                           To check the remediation rate of isolated microbes whether they are capable to remediate or not 1500mg/l nitrate concentration which is equivalent up to the reported nitrate concentration of Yamuna river. Phenotypic characterization These isolates were phenotypically characterized by biochemical tests like Gram stain, colony morphology, nitrate reduction, Indole production, Citrate test, Methyl red test, Voges Proskauer reaction and utilization of carbohydrates (Rita B et al 2009). IMVIC test and eight carbohydrate tests(Glucose, Adonitol, Arabinose, Lactose, Sorbitol, Mannitol, Rhamnose and Sucrose) were analysed using Hi-Media kit (KB001). Metabolic profiling of the microbes helps in identification. Identification of microbes using 16S rRNA gene sequence Isolation of Genomic DNA from Bacteria Each isolated colony was inoculated in 5ml Nitrate Broth and incubated at 37?C at 200rpm in a shaker incubator. 1.5ml bacterial culture was taken in a microcentrifuge tube and centrifuged at 4?C for 10mins at 4000rpm. After centrifugation, the supernatant was removed. Pellet was resuspended in 180µl of lysozyme solution (pH 8.0) followed by incubation at 37?C for 30mins till lysis was observed. Cells were kept at -80?C for 10mins. After that,30µl lysis solution (pH 8.0) was added and incubated in ice for 10mins. An equal volume of Phenol-Chloroform was added (1:1) to separate the DNA from the protein. The tube was centrifuged at 8000rpm for 5mins at 4?C to collect the upper layer.22 Upper layer was taken in another tube and chloroform (500 µl) was added and then again centrifuged. After centrifuging, the upper layer was collected in a new centrifuge tube and 1/10th part of 1M NaCl, 2-2.5 ethanol (absolute ethanol) was added. The tube was kept at -80?C for 30mins and further centrifuged at 10,000rpm for 30mins at 4?C. The supernatant was completely decanted and the DNA pellet was washed with 70% chilled ethanol. Pellet was centrifuged at 8000rpm for 5mins at 4?C then dry pellet and dissolved in 20µl TE buffer.23 Polymerase Chain Reaction The polymerase chain reaction was used to identify the microbes by isolating bacterial Genomic DNA using Sambrook protocol23,22Universal primer 27F(5`-AGAGTTTGATCCTGGCTCAG-3`) and 1492r (5`- CGGTTACCTTGTTACGACTT-3`) were used in amplification reactions, which were prepared in a total volume of 20µl with the following conditions: -10µl PCR master mix (Genei),0.4µl Primer F, 0.4µl Primer R, 2µl DNA template(50ng/µl) and 7.2µl Nuclease free water (Hyclone) was added. According to thermal profile 95?C 5mins, 95?C 1mins, 58?C 1mins, 72?C 2mins for 30 cycles and followed by 72?C 10mins in Simple Amplifier thermal cycler (Applied Biosystems) and analysed by 1% agarose gel electrophoresis and stained with ethidium bromide under UV light. Results Water Quality Assessment The physical parameters analysed were pH, colour, odour and turbidity (Table II) and the chemical parameters evaluated were Alkalinity, Hardness, chloride, TDS, Fluoride, Iron, Ammonia, Nitrites, Nitrates, Phosphates, Chlorine, BOD and COD. (Table III) Collection and isolation of bacterial species The observed concentration of nitrate in water samples collected from the Okhla barrage was found to be between 75-100mg/l.           Eleven different bacterial colonies (PP1-PP11)were identified initially from water samples collected from the Okhla Barrage site on a low concentration of nitrate (range start from 50mg/l). Four, out of these were tolerant to high concentrations of nitrate (up to 500mg/l). They were PP3, 5,7 & 10. The remediation potential of these strains was then checked. Remediation potential of Bacterial strains The four bacterial strains which showed tolerance against nitrate were selected to further check their nitrate remediation potential. They were marked as PP3, PP5, PP7 & PP10. 4% inoculum was inoculated in Nitrate broth and incubated at 37°C for 72hrs. After incubation, the optical density of each bacterial strain was measured at 420nm along with control. The nitrate remediation rate of each bacterial strain was checked. PP3, PP5, PP7 and PP10 showed negligible nitrate remediation under aerobic conditions. PP3,PP5,PP7 and PP10 showed remediation of 34.1%, 42.9%, 33.6% and 48.4% respectively under anaerobic conditions (Graph I). Each microbe was then phenotypically characterized.                                            Further, these four bacterial strains were inoculated in nutrient broth containing 1500mg/l nitrate and then incubated under the same above conditions to check their remediation rate. It was seen that PP5 and PP10 showed 44% and 46% nitrate remediation rates while the rest of the two PP3 and PP7 did show slight remediation potential. Phenotypic Characterization                                                                                                                                                                       All microbes were found to be Gram-negative and rod-shaped bacteria. They belong to the Enterobacteriaceae family based on the results of biochemical tests which are shown in Table IV. Genotypic characterization of microbes These isolates were chosen further to identify the genus and species of microbes and also check similarity percentage with strains using BLAST. Identification of isolates was done using phylogenetic analysis of 16S rRNA sequences. Genomic DNA and PCR band of isolates (PP3, PP5, PP7 and PP10) are shown in figure I. Phylogenetic analysis The partial 16S rRNA gene sequence of 1399 base pairs of strain PP10 sequence showed 99% similarity with Enterobacter aerogenes (KP764198). 1476 base pair of strain PP3 had 99% similarity with Lelliotiaamnigena and 1409 base pair of PP5 had similarity with E.coli K12. 1398 base pair of PP7 strain had similarity with Klebsiella oxytoca. A Phylogenetic tree was constructed using Clustal W (multiple sequence alignment) and MEGA software. The phylogenetic tree was inferred from 16S rRNA sequences data using neighbour-joining tree are shown in figure II. Nucleotide Sequence Accession Number The nucleotide sequence of isolates PP3, PP5, PP7and PP10 were deposited in the GenBank nucleotide sequence database under accession number MN647560, MN754025, MT457847, and MN252552 respectively. Statistical Analysis One-way analysis of variance(ANOVA) was used to compare among different groups. Microsoft Excel was used for data presentation. Each experiment was repeated three times in replicates. Mean and standard deviation were calculated and associated probability (P) Englishhttp://ijcrr.com/abstract.php?article_id=4137http://ijcrr.com/article_html.php?did=41371. Sharma S, Jha PK, Ranjan MR, Singh UK, Jindal T, Sakram G, et al. Nitrate removal efficiency of bacterial consortium (Pseudomonas sp. KW1 and Bacillus sp. YW4) in synthetic nitrate-rich water. Bioresour. Technol. [Internet]. 2017;157(2):553–63. Available from: http://dx.doi.org/10.1016/B978-0-12-818307-6.00010-X 2. Chadwick DR, John F, Pain BF, Chambers BJ, Williams J. Plant uptake of nitrogen from the organic nitrogen fraction of animal manures: A laboratory experiment. J Agric. Sci. 2000;134(2):159–68. 3. Savci S. An Agricultural Pollutant?: Chemical Fertilizer. Int. J. Environ. Sci. Technol 2012;3(1):11–4. 4. Galloway JN, Townsend AR, Erisman JW, Bekunda M, Cai Z, Freney JR, et al. Transformation of the nitrogen cycle: Recent trends, questions, and potential solutions. Science (80- ). 2008;320(5878):889–92. 5. Brender JD, Weyer PJ, Romitti PA, Mohanty BP, Shinde MU, Vuong AM, et al. Prenatal nitrate intake from drinking water and selected birth defects in offspring of participants in the national birth defects prevention study. EnvironHealth Perspect. 2013;121(9):1083–9. 6. Kim HR, Yu S, Oh J, Kim KH, Lee JH, Moniruzzaman M, et al. Nitrate contamination and subsequent hydrogeochemical processes of shallow groundwater in agro-livestock farming districts in South Korea. Agric. Ecosyst Environ [Internet]. 2019;2720:50–61.Available from: https://doi.org/10.1016/j.agee.2018.12.010 7. The D, Parameters C, Quality OF, Drinking OF, In ACS. OF QUALITY OF DRINKING WATER?; A CASE STUDY in Int. J Curr Res Rev. 2011;03(09):33–6. 8. Lin B Le, Sakoda A, Shibasaki R, Suzuki M. A modelling approach to global nitrate leaching caused by anthropogenic fertilisation. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareMachine Learning and Data Analytics based Analysis for Heart Disease Prediction English6569Patil Rina S.English Gangwar MohitEnglishThe heart is the subsequent major organ connecting to the brain, which has stronger precedence in the human evidence. It elevates the blood and accumulations to all devices of the entire body. Forecast of circumstances of heart conditions in the medical field is important to work. Data analytics is beneficial for divining more knowledge, and it helps the medical centre predict various conditions. A huge number of patient-related data is prepared each month. The collected data can be beneficial for the source of predicting the emergence of future weaknesses. Unusual data mining and machine learning procedures have been used to indicate heart disease. This research proposed heart disease prediction using various modified Recurrent Neural Network (mRNN) deep learning algorithms. Numerous feature extraction and selection methods have been used to get important features and data collection using custom-generated IoT environments. The system effectively provides heart risk scores with the highest accuracy in a runtime environment. English Internet of Things, Deep Learning, Feature selection, Feature extraction, Optimization, Classification, Supervised learningIntroduction Health data mining provides immense promise to discover the secret trends in the scientific domain names data sets. For psychiatric disorders, these structures can be used. The providing raw patient records are therefore widely dispersed, homogenous, and weighty. It is useful to acquire such data in a structured manner. The health monitoring system, data gathered can then be incorporated. A user-oriented methodology to new and secret trends in the information is generated by business intelligence. It has been estimated from the WHO that 12 million people die internationally each year due to heart failure. Related to cardio-related disease, half the deaths in the USA and other developing nations occur. It is also the primary cause of casualties in many developed countries. Most of all, it is considered the main reason for deaths worldwide. The word High Cholesterol includes the different diseases that cause the condition. The main cause of fatalities in various countries such as Sri Lanka was breast cancer. In the Western World, heart illness kills one adult every 34 seconds. Other types of heart disorders include coronary heart disease, cardiomyopathy and cardiovascular disease. A wide variety of conditions influencing the cardiovascular framework and how air is filtered and distributed through the body are included in the word &#39;cardiovascular disease.&#39; Several diseases, injuries and deaths arise from cardiovascular disease (CVD). A critical and complicated role in medication is the diagnosis of disorders. Psychological care is an essential but complex task that remains to be improved precisely and effectively. This program&#39;s automation would be highly beneficial. Regrettably, in any sub-speciality, all physicians do not have the experience. Besides, there is a lack of staff at some sites. Therefore, putting all of them together, and an automated medical diagnosis scheme would possibly be extremely helpful. Reasonable judgment on computer-based knowledge Help networks will support the achievement of clinical studies at a lower cost. A comparative analysis of the different technologies applied includes effective and precise implementations of the electronic machine. This paper aims to analyze the various statistical and machine learning strategies for evaluating machine learning introduced in the past months. Review of Literature This section focused on the study of various existing systems, and the work has done by various existing research in IDS A new deep learning model for sex and age identification using a standard inertial sensor is suggested by Sun et al. (2019).1 This approach is assessed with data obtained from more than 700 individuals using the highest sensor-based training repository value. Ten experiments of Monte-Carlo test sets were given to confirm the robustness and efficacy of the presented method. In protection applications, such as cell phone authorization, biometrics has been commonly embraced. The reliability of hard biometrics-standard physiological properties like face, including fingerprint and behavioural factors such as visual features and voice-is also the subject of these implementations. A supervised neural technique uses a single inertial sensor attached to the lower back of gender and age recognition issues. Machine learning-based techniques have been commonly used throughout vision-based gender detection. Still, they haven&#39;t been used for electromagnetic sensor-based gender acknowledgement to our best understanding. According to Lo et al.2, a point fulfilment network utilizes a specific dimensional image taken from every suitable angle of view to perform 3d model of objects. The suggested technique has resolved many primary problems in vision-based disease diagnosis relative to previous methods, such as view deformation and scale uncertainty. For testing this method, various experiments were carried out. Still, the feasibility of SVM and NB, the algorithm was demonstrated in the robust prediction. Tested objects have asked to remember the complete description of food products eaten over the last 24 hours and the corresponding portion sizes to measure the calorie consumption. The size of both the food component relies mainly on the entity&#39;s personal opinions, which is often too unreliable. Under the circumstances of view occlusion, this approach demonstrates the effectiveness and accuracy of food volume estimation. The finished pixel value of the obstructed food products can be accessed by using the point fulfilment network. According to Uddin and Hassan3, a comprehensive approach to healthcare monitoring activity recognition using body receptors and a complex Convolutional Neural Network called CNN. They analyze signals from various body sensors in healthcare services, like ECG, wearable sensors, and control system sensors. A CNN Based operation is equipped based on the features after removing essential characteristics from the wearable sensors based on PCA. Eventually, the deeply educated CNN was used for the identification of data testing events. A publicly accessible standard dataset is applied to the defined solution and then contrasted with other traditional methods. The experimental of these system findings suggests that the counsel made is superior to others, showing both approaches&#39; robustness to be implemented in the environment sensor-based intelligent health systems for behavioural assisting. As a growing field of study, esteemed solutions to implementing a comprehensive smart healthcare delivery system for individuals to extend their independent lives must now be explored. The detectors were positioned on the neck, right wrist, or left ankle of the subject, separately, and connected using elastic bands. Several sensors help us quantify the movement experienced by different body parts, including momentum, turn frequency, and direction of the gravitational flux, thereby better measuring the body&#39;s nature. According to Ganesan and Sivakumar,4 a fresh Cloud and IoT-based Healthcare application were developed to monitor and diagnose serious diseases. In the training phase, the classifier was trained using the data from the benchmark dataset. During the testing phase, the actual patient data to identify disease was used to identify the presence of disease. According to Majumder et al.,5 proposed a multiple sensors system using a smart IoT that gives an early warning of disease risk, constantly collects the data from the user, and sends it to the smartphone via Bluetooth using Body Area Sensor (BAS) system. All the processing and data analysis took place in the application to view real-time user plots of future cardiac arrest. An IoT system with a low power consumption communication model developed regularly collects body temperatures and heart rate using a smartphone. Here ML and signal processing techniques were used to analyze sensor data and predict high accuracy cardiac arrests. A wearable device was implemented based on a smartphone for heart rate detection. It used a combination of ECG and body temperature. A heart rate analysis is done on the Android platform where users can view body temperature and plots of real-time ECG signals. According to Yu et al.6 an adversarial training approach is proposed to multitask learning to estimate multi-type Cardiac Indices in MRI and CT. By using multitask learning networks, these task dependencies are shared and learned. Lastly, they transferred parameters learned from MRI to CT. A series of experiments were performed. The authors first optimized system efficiency over 2900 cardiac MRI images through ten-fold cross-validation. Then the network was run on an independent data set with 2360 cardiac CT images. The results of all experiments on the proposed reverse mapping indicate excellent performance in estimating multiple cardiac indices. Ali et al.7 implemented an optimally designed OCI- DBN, a deep belief network to resolve these problems and boost system performance. They used Ruzzo-approach Tompa&#39;s to delete features that do not contribute enough to boost processing speed. They stacked evolutional algorithms stacking two genetic algorithms to have an optimally designed DBN to obtain maximal configuration settings. To provide an insight into how the system operates, an RBM and DBN study was conducted. According to Kumar et al.8 cloud-based and IoT-based m-healthcare applications have been produced and updated to observe and diagnose the genuine level of severity. To gather medical data in remote areas, such instruments are used. The approximate estimate can be collected as vital information, connected to the human body, gained from IoT devices. They were using the UCI Repository dataset and clinical sensors to foresee the average person with a major influence on non-communicable diseases medicinal knowledge is produced. The resulting information is securely stored by implementing a new federal storage method in five different steps, such as data storage, data recovery, data gathering, database division, and file merging. According to Park et al.9 a smart wheelchair method was installed that monitors but visualizes the user&#39;s location through a mobile app that attempts to address the inconsistent position of the user. They used strain gauges and shift sensing, using IoT and Wireless techniques to communicate with low consumption. It&#39;s an extension of Arduino that detects various user stances. This integration complements the user by offering real-time interactive and visualized data for mobile apps to sit properly and understand their present incarnation. With pressure displayed in red, yellow, pink and green triangles. This is a great example of Information systems. Kumar and Devi10 introduced IoT&#39;s three-tier architecture with early detection using a supervised learning algorithm to detect cardiac disease. This system also suggested multi-tier architectures that stored and processed massive quantities of data from wearable IoT environments. First-tier focuses on data collection from numerous analogue sensors; Tier two demonstrates Apache Hadoop that stores vast quantities of data into the cloud storage, while Tier three uses Apache-based Mahout to build a logistics learning base detection as well as a prediction model. In conclusion, ROC demonstrates to get entire system analysis of heart disease prediction. Nashif et al.11designed a disease prediction system based on the cloud. A real-time monitoring system sensing health parameters like blood pressure, temperature, heartbeat and humidity was developed using an Arduino microcontroller. The proposed system can detect heart disease using ML techniques as recorded data transmitted to a central server is updated every 10 seconds.   Santhi and Renuka12 implemented an optimized prediction model using a genetic algorithm. They studied various prediction models and important feature selection algorithms. Its performance is better than other traditional prediction models. The various prediction models were retested with heart disease data sets and validated with real-time data sets. The n–cross-validation methodology is applied to produce balanced training and testing data set. Alotaibi 13 used the Rapid miner tool and various ML approaches to improve the previous accuracy score and to predict heart disease. UCI heart disease dataset was tested. The proposed work improved the previous accuracy score. Proposed works System Architecture According to many factors, the medical remote management forecast period demand has expanded significantly. When it is very common today in developing countries that older adults typically live separately in their own homes, the elderly population is growing. Besides, the Internet of Things (IoT) makes these remote patient monitoring systems theoretically feasible (IoT as the idea of a capable and modifiable environment of surveillance in which controls or actuators to human and non-living particles) and makes it financially viable because of the even lower expense of sensors. Because of the advent of smart mobile technology, this is also understood that consumers are now prepared to embrace these types of solutions that capture private and sensitive data from people in real-time, such as temperatures, blood glucose, breathing, mass spectrometry sensor, to name a few. For example, personal health observers such as smart beds instantly notify who is utilizing them. More, they are sure to enlighten different patients&#39; physical levels, making real smart home drug dispensers automatically warn when medication is not taken, for example. Several virtual care monitoring devices use various technologies inside facilities and their residences to monitor and/or track clinicians or diagnostic applications. Regrettably, most of these systems are not versatile when new sensors are introduced during runtime, as far as we know. Neither has it allowed regular users with the smart technologies added to generate ad-hoc notifications automatically. Distributed data processing is one of the processes involved that can resolve a number of the protection, distribution, integration, and management challenges of aggressive data innovation. For a genuine analysis and diagnosis system that results in incredible medicinal implementations, the primary requirement for continuous and limitless access to patient details from anywhere and from any computerized gadget is necessary. This propels current research towards thinking about pervasive clinical frameworks focused on the internet. The Predictive Analytic System hardware implementation predicts that disease relative to body temperature, pulse rate, and individual tension. The sensors are mounted on the human chest to monitor the physician&#39;s metabolic rate, heart rate, cholesterol levels. It sends data from the information it predicts and diagnoses the disease to the Arduino microcontroller. This information is hosted in the cloud via the end receiver. It can be monitored and anywhere whenever through the internet. The condition of the physician will be registered on the database and retained. A smartphone framework for machine learning is designed for viewing data from sensors and sending emergency alerts. Healthcare practitioners can track, anticipate, diagnose, and inform their clients at any moment by using this method. The conceptual system can control several predictor variables on wearable technology, integrated with such a handheld device. Sensor networks work together again to obtain the necessary data, except encountered some problems. It operates by reducing less human involvement to preserve its precision. Using cardiovascular sensors is a legitimate diagnostic device for remote areas heart-prone clinicians that monitor heart rate, cholesterol levels, metabolic rate, and many other metrics. N number of measurements obtained can be preserved and viewed subsequently by practitioners to correct acute and chronic treatment as depicts in Figure 1. The methodology of computer vision will sensitize and evaluate the teaching context to inculcate heart performance. Two major physician and patient interfaces would allow data to be transmitted to each other. In actual environments, this system recognizes fundamental heart problems for the sake of the health of the individual. It produces alarm in the sense of Text messaging, email, etc. based between high and low input parameters set a right for a physician and any close relative registered liable. It&#39;ll also enrich that system with a sense of focus and consideration that adds value to the condition of the individual. Algorithm Design Algorithm 1: Proposed modified Recurrent Neural Network Algorithm (mRNN) Input:  Train_Feature set {} which having values of numeric or string of training dataset, Test_Feature set {} which having values of numeric or string of test dataset, Threshold denominator Th, Collection List cL. Output: classified all instances with the desired weight. Step 1: Read all features from the Testing dataset using the below function Step 2: Read all features from the training dataset using the below function Step 3: Read all features from Trainset using below Step 4: Generate the weight of both feature set Step 5: Verify with Th Selected_Instance= result = Weight >Th ?1 : 0; Add each selected_instance into cL, when n = null Step 6: Return cL Results The proposed research focuses on the soft computing approach and classification-based recognition, fundamentally this approach consuming the respectable exposure rate, nevertheless generating sometimes more false-positive ratio. Figure 2 below displays the 3-fold classification technique used on all parameters and explains all implementation consistency. The above Figure 2 improves the importance of different experimental research focusing on various statistical tests with seven distinct algorithms: Fuzzy Logic, Q-Learning, Naïve Bayes, Linear Regression, ANN and Random Forest with Recommended Perceptron Algorithm. Discussions The proposed system makes sense to interrelate quantitative assessment and clinical scores and could potentially address many challenges in decision-making. The generated training repository was applied with six machine learning models to establish patterns of common, questionable and dangerous activities. To test and rate the machine learning strategies, the 3-fold, 5-fold and 10-fold cross-validation model was employed using the behaviour classification, training database. For data management, the mRNN classification algorithm was used during the classifier. The neural network was shown and debated for each model. Both uncertainty metrics show the system accuracy of properly classifying, wrongly classifying, recession, and device recall. Conclusions This study introduced an ideal framework for prediction models in real-time. Users with the coronary disease can use that. Unlike many other systems, it is capable of tracking and predicting both. The system&#39;s diagnostic method will predict cardiovascular disease utilizing ML algorithms. The predictive conclusions are based on the dataset example of heart disease. On the other hand, the device is very economical; we used an enthused pulse sensor and sent the data via the Arduino suite microcontroller to mobile devices. To check the variances and raise the alarm if the patient&#39;s heart rate increases above the usual heart rate. To prove the system&#39;s efficacy, we performed tests with both the tracking and diagnostic method. We conducted experiments with supervised machine classification methods such as QL, Linear Regression, Random Forest, Naive Bayes, ANN and Fuzzy Logic, etc. The procedure was done with the validation set test, and 89% efficacy of the proposed method was obtained for mRNN. To extract various feature extraction and selection with embedded deep learning techniques will be an interesting future work for the system. Acknowledgement The authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed Source of Funding: Self. Conflict of Interest: None. Authors’ Contribution: Ms. Patil performed the data analysis and developed the overall paper under the supervision of Dr. Gangwar Englishhttp://ijcrr.com/abstract.php?article_id=4138http://ijcrr.com/article_html.php?did=4138[1] Sun Y, Lo FP, Lo B. A deep learning approach on gender and age recognition using a single inertial sensor. In2019 IEEE 16th International Conference on Wearable and Implantable Body Sensor Networks (BSN) IEEE.2019; 19:1-4. [2] Lo FP, Sun Y, Qiu J, Lo B. A novel vision-based approach for the dietary assessment using deep learning view synthesis. In2019 IEEE 16th International Conference on Wearable and Implantable Body Sensor Networks (BSN) IEEE. 2019 May 19 :1-4. [3] Uddin MZ, Hassan MM. Activity recognition for cognitive assistance using body sensors data and deep convolutional neural network. IEEE Sensors Journal. 2018 Sep 20;19(19):8413-9. [4] Ganesan M, Sivakumar N. IoT-based heart disease prediction and diagnosis model for healthcare using machine learning models. In2019 IEEE International Conference on System, Computation, Automation and Networking (ICSCAN) 2019 Mar 29 (pp. 1-5). IEEE. [5] Majumder AK, ElSaadany YA, Young R, Ucci DR. An energy-efficient wearable smart IoT system to predict cardiac arrest. Advances in Human-Computer Interaction. 2019;2(12);2019. [6] Yu C, Gao Z, Zhang W, Yang G, Zhao S, Zhang H, Zhang Y, Li S. Multitask learning for estimating multitype cardiac indices in MRI and CT based on adversarial reverse mapping. IEEE transactions on neural networks and learning systems. 2020 Apr 16. [7] Ali SA, Raza B, Malik AK, Shahid AR, Faheem M, Alquhayz H, Kumar YJ. An Optimally Configured and Improved Deep Belief Network (OCI-DBN) Approach for Heart Disease Prediction Based on Ruzzo–Tompa and Stacked Genetic Algorithm. IEEE Access. 2020 Apr 3;8:65947-58. [8] Kumar PM, Lokesh S, Varatharajan R, Babu GC, Parthasarathy P. Cloud and IoT based disease prediction and diagnosis system for healthcare using Fuzzy neural classifier. Fut Gen Compt Sys. 2018 Sep 1;86:527-34. [9] Park M, Song Y, Lee J, Paek J. Design and implementation of a smart chair system for iot. In2016 International Conference on Information and Communication Technology Convergence (ICTC). IEEE. 2016;19:1200-1203. [10] Kumar PM, Gandhi UD. A novel three-tier Internet of Things architecture with a machine learning algorithm for early detection of heart diseases. Compt Elect Engg. 2018 Jan 1;65:222-35. [11] Nashif S, Raihan MR, Islam MR, Imam MH. Heart disease detection by using machine learning algorithms and a real-time cardiovascular health monitoring system. World J Engg Tech. 2018 Sep 12;6(4):854-73. [12] Salem T. Study and analysis of prediction model for heart disease: an optimization approach using genetic algorithm. Int J Pure Appl Mathem. 2018;119(16):5323-36.. [13] Alotaibi FS. Implementation of a machine learning model to predict heart failure disease. Int J Adv Compt SciAppl. 2019;10(6):261-8..

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareStudy of Ocular Manifestations in Systemic Malignancies English7075Khochikar Nilima M.English Karambelkar VHEnglishIntroduction: Primary ophthalmic tumours are well known, but the eye is a rare site for disseminated malignancy. The eye and orbit can get affected by cancer due to the direct effect of metastatic neoplastic infiltration or compression or by circulating anti-bodies involving paraneoplastic retinal degeneration. Aim: The present study aims to objectify the ocular manifestations in systemic malignancies. Methodology: This cross-sectional study was conducted on patients presenting with systemic malignancies to the out-patient department of Krishna Hospital Karad, Maharashtra, from December 2018 to May 2020. Result: Ophthalmic manifestations were seen in 21.77% of patients with systemic malignancies. Conclusion: All patients with systemic malignancies (primary and metastatic) should undergo a thorough ophthalmic examination regularly to prevent visual loss. English Ocular manifestations, Systemic malignancies, Metastatic, Visual loss, Ophthalmic, AntibodiesINTRODUCTION: Primary ophthalmic tumours are well known, but the eye is a rare site for disseminated malignancy. The eye and orbit can get affected by cancer due to the direct effect of metastatic neoplastic infiltration or compression or by circulating antibodies involving paraneoplastic retinal degeneration. Hematogenous and direct spread also do account for the ocular manifestations of systemic malignancies.1 Metastatic tumour to the uvea is the most common form of presentation. The choroid is the most common site for uveal metastasis. Iris and ciliary body metastases are present in 10% of cases. Retina, optic disc, vitreous, and conjunctiva are affected when there is already uveal tract involvement. Choroidal metastases are associated with an unusually large amount of subretinal ?uid presenting as complete retinal detachment and or a mass on ocular ultrasound.1 In cases of space-occupying lesions, papilledema, abducent nerve palsy, nystagmus and optic atrophy are the most common presenting signs.2 Breast and lung carcinomas for women and lung and gastrointestinal (GI) carcinomas for men most commonly metastasize to the eye and orbit. The incidence of metastasis to the eye from breast cancer is around 47%, from lung cancer is around 21%, and that from the GI tract is around 4%. Melanoma, urological malignancies also manifest with ocular metastasis. Most patients presenting with ocular metastases already have a history of treated primary cancer. However, approximately 1/3rd of patients has no history of primary cancer viz. primary adenocarcinoma of the lung, which can present for the ?rst time with ocular metastases in up to 50% of cases.1,3,4 Metastasis to the eye and orbit and paraneoplastic disorders represent a very bad prognostic sign. The average survival following a diagnosis of uveal metastases is 7 months.3 As the incidence of malignancy is on the rise in India, it is important to study the ocular manifestation of these non-ocular malignancies especially when there is sparse literature on this. The majority of the studies conducted in the past were autopsy studies. Early and prompt diagnosis with appropriate investigations and apt treatment can restore the vision and improve the quality of life in these unfortunate patients. Therefore, this research was conducted to study the occurrence and clinical features of ocular manifestations in systemic malignancies. METHODOLOGY: This cross-sectional study was conducted on patients presenting with systemic malignancies to the out-patient department of Krishna Hospital Karad, Maharashtra, from December 2018 to May 2020. According to a study “ocular-metastases”,5 the proportion of ocular manifestations in systemic malignancies is 10%. Therefore, by using formula – N=4PQ/L,2 where P=10%, Q= 100-P (90%), L=4%, at 95% confidence interval, the sample size comes up to 225. Patients with primary ophthalmic tumours and malignancies arising from radiation were excluded. Data entry was done in Microsoft excel 2019 and imported to SPSS version 21.0 for data analysis. The p-values were considered statistically significant if and when p > 0.05. The ethical clearance has been given and by protocol number 0236/2018-2019). RESULTS: This cross-sectional study including 225 participants with systemic malignancies yielded the following results. Baseline characteristics: The mean age of patients in the study population was 52.32 ± 20.26 years. The majority of 113 (50.2%) patients were in the age group of 51-75 years. Ophthalmic manifestations were seen in 49 patients (21.77%) of which, 31(63%) were males and 18(37%) were females. The primary malignancies in which ophthalmic manifestations were seen are depicted in Figure 1. The most common primary malignancy was Head and Neck malignancy (28.57%), followed by breast (24.48%), genitourinary tract (20.40%), hematopoietic (10.20%), lung (8.16%), bone (4.08%), skin and endometrium (2.04%). Table 1 shows the list of ophthalmic manifestations in the patients. The different primary malignancies have different tissues of preference in the eye. The details are depicted in Table 2. More cases in the intraocular group 28 (57.14%) as compared to adnexa group 21(42.86%) respectively. There was no significant difference among any of the study variables (malignancies) with ocular manifestation (p>0.05). Various malignancies affect different structures in the eye. Ca. the breast had ocular manifestation in the posterior segment (8.16%), adnexa (8.16%) and CNS manifestation (8.16%), but no manifestation in the anterior segment. Ca. Lung had ocular manifestation in the posterior segment (2.04%) and CNS manifestation (6.12%), but no manifestations in the anterior segment and adnexa. Haemopoietic malignancies (10.20%) and Bone cancers (2.04%) had ocular manifestation only in the posterior segment. The genitourinary tract had ocular manifestations in the anterior segment (2.04%), posterior segment (6.12%), adnexa (10.20%) and CNS manifestations (4.08%). Head neck cancers manifested in the adnexa (10.20%) and had CNS manifestations (18.37). DISCUSSION: This observational study was conducted on 225 patients. Ocular manifestations were seen in 49 (21.77%) patients. The mean age of these patients was 54.2 ± 22.39 years, of which 61% were males and 39% were females. Ocular metastasis is often detected late because the patients may not have any visual symptoms or the systemic symptoms may be too severe.5 Even in our study the majority of our patients, i.e., 41% presented within 6 months to two years of being diagnosed with malignancy. Around 37% presented later than two years. Shah et al., in their study of 187 patients with uveal metastasis from lung cancer reported that the mean age at presentation was 62 years. The mean interval between the diagnoses of lung cancer and uveal metastases was around 2.5 years.6 In our study, most of the ocular metastasis was from head and neck malignancy (28.57%), followed by breast (24.48%), genitourinary tract (20.40%), hematopoietic (10.20%), lung (8.16%), bone (4.08%), skin and endometrium (2.04%). Among the head and neck cancers like Ca larynx presented with LR palsy (6.1%) and ptosis (4.1%), Ca Maxilla presented with proptosis (8.2%), Ca Ethmoid also presented with proptosis (2.04%), Temporal Lobe Glioblastoma presented with LR Palsy (2.04%), astrocytoma of the temporal lobe (R) and left parietal lobe astrocytoma presented with Papilledema (2.04% each), and left temporal lobe astrocytoma presented with optic atrophy (2.04%). Similar to our study, Yan and Gao in their retrospective study of 35 males and 11 females with a mean age of 47 years, also reported head and neck cancers (nasopharyngeal carcinoma, 30.34%) as the most common malignancy with ocular manifestations. Other head and neck cancers were medullary thyroid carcinoma (2.17%) and lacrimal gland carcinoma (2.17%). The most common ocular presentations were abnormal eye position (65.22%), followed by proptosis (63.04%), increased orbital pressure (54.35%), diplopia (54.35%), and decreased ocular motility (52.17%).7 The incidence of ocular metastasis with primary breast cancer ranges between 5 and 30%.8,9 In our study it was 24.48%. The most common ocular manifestation in breast carcinoma was proptosis, followed by choroidal METS, Lateral rectus palsy, ptosis, and retinopathy. Kreusel et al. reported intraocular metastasis in 4.6% of patients with breast cancer with the choroid being the most common site.9 Supriya and Lokesh reported a case of Exudative Retinal Detachment in a 38-year-old female with adenocarcinoma of the breast. It was characterized by the collection of sub-retinal fluid with no retinal breaks or traction. 10 Madanagopalan et al. reported a rare case of CRVO in a case of breast carcinoma where the retina showed extensive haemorrhages and dilated retinal veins. 11 Francone et al. 12 and Maliepaard et al. 13 reported cases where ocular metastases were the primary presentation of breast cancer. The incidence of ocular metastasis with primary lung cancer is reported to be 0.2% to 7%.6,14 In our study it was 8.16%. Similar to our study, Yan and Gao reported an incidence of that 8.6%.7 In a review of 950 uveal metastases by Shields et al. the incidence of ocular metastasis with primary in the lung was reported in 21% cases.15 The most common ocular manifestations seen in our study were LR Palsy, Ptosis, and Carcinoma Associated with Retinopathy (CAR). They are more common in men. Contradictory to our study, Shah et al. reported that choroid was the commonest involvement (88%), followed by iris (10%) and ciliary body (2%).6 Hoang et al. and Hernández-Da Mota et al. reported ocular metastasis as first presentation in older male patients due to metastatic lung adenocarcinoma.16,17 Many case studies are reported where the first clinical presentation was ocular in case of primary in lung. 18,19 Ocular manifestations in haematological malignancies are well documented now. In our study, sub-hyaloid haemorrhage (10.2%) was the only ocular manifestation that was seen in such malignancies. Similar to our findings, Koshy et al. reported a prevalence of 10.4% for sub hyaloid haemorrhages in patients of acute/chronic leukaemia.20 Carcinoma of the Genito-urinary tract can also present with ocular metastasis. In our study, Ca Prostate presented with proptosis (10.20%), LR Palsy and ptosis (2.04% each), Ca Urinary Bladder presented with Choroidal Mets (4.1%), and RCC presented with Choroidal Mets (2.04%) too. Uluocak et al. reported a metastatic orbital cancer secondary to prostatic adenocarcinoma in a 73-year-old man presenting with a history of ipsilateral visual loss and one-sided proptosis, periorbital swelling, and pain. 21 Lefresne et al. also reported an 81-year-old man with poorly differentiated carcinoma prostate who presented with pain, proptosis, and blindness.22  Pompeu et al. reported two cases where one patient presented with a mass in the eye and another with an ulcerated lesion on the inferior tarsal conjunctiva both of whom had primary RCC. 23 Hart et al. reported a 70-year-old man with persistent lateral rectus mass and orbital haemorrhage after retrobulbar anaesthesia. On biopsy, the lesion was found to be metastatic RCC. 24 Patil et al. reported a case of a 43-year-old male with sudden onset of binocular diplopia on lateral gazes. The patient showed features of ipsilateral one?and?a?half syndrome and investigations further revealed primary RCC. 25 Mitsui et al. reported a case of a 43-year-old bladder cancer patient, 17 months post radical cystectomy with a choroidal disorder and multiple nodules in the abdomen and head. On biopsy, it was revealed as a metastasis from the bladder cancer. 26 In another case report by Wiltshire et al. an 88-year-old man presented with acute loss of vision due to choroidal metastasis. A diagnosis of primary urothelial carcinoma of the bladder was later made.27 Therefore, it is necessary that in an older male with visual and urinary symptoms, the genitourinary system should be evaluated as a potential primary site. In our study, a case of Osteogenic Sarcoma and Mandibular Sarcoma presented with Sub hyaloid Hemorrhage (2.04% each). Very few case reports are published in this area. Agarwal A. reported a case of orbital metastasis presenting as proptosis in osteosarcoma.28 Rajabi et al. reported a case of a 55-year-old male known case of scapular bone osteosarcoma presenting with pain, decreased vision, proptosis, conjunctival injection, and chemosis.29 Other systemic malignancies that can present as ocular metastasis are the Gastrointestinal tract30 and skin. 31 In our study a patient presented with ocular symptoms like ptosis, exposure keratopathy, and optic atrophy whose primary was squamous cell Carcinoma of the lid. We found no ocular manifestation in Gastrointestinal malignancies. CONCLUSION: Ophthalmic manifestations were seen in 21.77% of patients with systemic malignancies. So, to conclude, the authors believe that all patients with systemic malignancies (primary and metastatic) should undergo a thorough ophthalmic examination regularly in a time framed manner to diagnose asymptomatic patients with ocular involvement at the earliest and prevent visual loss.  Acknowledgement: We acknowledge the contribution of our university and department for the unending support. Conflict of Interest: There is no conflict of Interest  Source of Funding: No Source of Funding Authors Contribution: This is a collaborative work among all authors. Khochikar Nilima .M.  & Karambelkar V.H., performed the statistical analysis, wrote the protocol, and wrote the first draft of the manuscript. Khochikar Nilima M.  managed the literature searches too. Both the authors read and approved the final manuscript. Englishhttp://ijcrr.com/abstract.php?article_id=4139http://ijcrr.com/article_html.php?did=41391. Bloch RS, Gartner S. The incidence of ocular metastatic carcinoma. Arch. Ophthalmol.. 1971 Jun 1;85(6):673-5. 2. Alswaina N, Elkhamary SM, Shammari MA, Khan AO. Ophthalmic features of outpatient children diagnosed with intracranial space-occupying lesions by ophthalmologists. Middle East Afr. J. Ophthalmol. 2015 Jul;22(3):327. 3. De Potter P. Ocular manifestations of cancer. Curr Opin Ophthalmol. 1998 Dec 1;9(6):100-4. 4. Georgalas I, Paraskevopoulos T, Koutsandrea C, Kardara E, Malamos P, Ladas D, Papaconstantinou D. Ophthalmic metastasis of breast cancer and ocular side effects from breast cancer treatment and management: mini-review. BioMed Res. Int.. 2015 May 11;2015. 5. Cohen VM. Ocular metastases. Eye. 2013 Feb;27(2):137-41. 6. Shah SU, Mashayekhi A, Shields CL, Walia HS, Hubbard III GB, Zhang J, Shields JA. Uveal metastasis from lung cancer: clinical features, treatment, and outcome in 194 patients. Ophthalmology. 2014 Jan 1;121(1):352-7. 7. Yan J, Gao S. Metastatic orbital tumors in southern China during an 18-year period. Graefe’s Arch Clin Exp Ophthalmol. 2011 Sep;249(9):1387–93. 8. Nelson CC, Hertzberg BS, Klintworth GK. A histopathologic study of 716 unselected eyes in patients with cancer at the time of death. Am. J. Ophthalmol. 1983 Jun 1;95(6):788-93. 9. Kreusel KM, Wiegel T, Stange M, Bornfeld N, Foerster MH. Intraocular metastases of metastatic breast carcinoma in the woman. Incidence, risk factors and therapy. Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 2000 May 1;97(5):342-6. 10. Supriya BN, Lokesh HM. A rare case of unilateral carcinoma of breast manifesting as an exudative retinal detachment-A case report. Res J Med Allied Heal Sci. 2019 2(2):28–9. 11. Madanagopalan VG, Selvam VP, Sivan NS, Govindaraju NV. Central retinal vein occlusion in a patient with breast carcinoma. GMS ophthalmology cases. 2019;9. 12. Francone E, Murelli F, Paroldi A, Margarine C, Friedman D. Orbital swelling as the first symptom in breast carcinoma diagnosis: a case report. J. Med. Case Rep. 2010 Dec;4(1):1-2. 13. Maliepaard M, Mesham M, Aleksic Z, Scholtz R, Edge J. Ocular metastasis as initial presentation in breast cancer. South African Med J. 2017 Aug 1;107(8):694–6. 14. Kreusel KM, Bechrakis NE, Krause L, Wiegel T, Foerster MH. Incidence and clinical characteristics of symptomatic choroidal metastasis from breast cancer. Acta ophthalmologica Scandinavica. 2007 May;85(3):298-302. 15. Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology. 1997 Aug 1;104(8):1265-76. 16. Hoang A, Khine KT, O’Rese JK, Tesser RA, Chesnutt DA. A rare ocular presentation of metastatic lung cancer: unilateral anterior chamber angle, bilateral choroidal, and multiple intracranial metastases. J. Glaucoma. 2017 Feb 1;26(2):e93-5. 17. Hernández-Da Mota SE, Ulaje-Nuñez JM, Salinas-Gallegos JL, Rodríguez-Reyes A. Iris metastasis as a first manifestation of lung adenocarcinoma. Archivos de la Sociedad Española de Oftalmología (English Edition). 2018 Jul 1;93(7):357-9. 18. Maturu VN, Singh N, Bansal P, Mittal BR, Gupta N, Behera D, Gupta A. Combination of intravitreal bevacizumab and systemic therapy for choroidal metastases from lung cancer: report of two cases and a systematic review of the literature. Medical Oncology. 2014 Apr 1;31(4):901. 19. Jiang K, Brownstein S, Sekhon HS, Laurie SA, Lam K, Gilberg S, Britton W. Ocular metastasis of lung adenocarcinoma with ELM4-ALK translocation: A case report with a review of the literature. Saudi J Ophthalmol. 2013 Jul 1;27(3):187-92. 20. Koshy J, John MJ, Thomas S, Kaur G, Batra N, Xavier WJ. Ophthalmic manifestations of acute and chronic leukaemias presenting to a tertiary care centre in India. Indian J. Ophthalmol. 2015 Aug;63(8):659. 21. Uluocak N, Suha Parlaktas B, Ersay Deniz F, Erdemir F, Dogan Koseoglu R, Gedar MO. Orbital metastasis of prostate cancer: a case report. Kaohsiung J Med Sci. 2007 Apr;23(4):199-202. 22. Lefresne S, Fairchild A, Johnson R, Deschenes J, Russell L, Pederson J. Genitourinary malignancy presenting as an ocular metastasis: a case report and review of the literature. Can Urol Assoc J . 2012 Apr;6(2):E67. 23. Pompeu AC, Arap S, Silva MN, Monteiro DS. Ocular metastasis as the first presentation of renal cell carcinoma: report of 2 cases. Clinics. 2005 Feb;60(1):75-8. 24. Hart RH, Luthert PJ, Rose GE. Renal cell carcinoma metastasis masquerading as a recurrent orbital haematoma. Orbit. 2005 Dec 1;24(4):281–4. 25. Patil M, Ganger A, Sharma S, Saxena R. Metastatic renal cell carcinoma presenting as a one-and-a-half syndrome. Indian J Ophthalmol. 2017 Sep;65(9):895. 26. Mitsui Y, Arichi N, Inoue K, Hiraki M, Nakamura S, Hiraoka T, et al. Choroidal and Cutaneous Metastasis from Urothelial Carcinoma of the Bladder after Radical Cystectomy: A Case Report and Literature Review. Case Rep Urol. 2014;2014:1–4. 27. Wiltshire KL, Laperriere N, Bristow RG. Prolonged survival in a patient with choroidal metastases from urothelial bladder cancer. Can J Urol. 2009 Aug;3(4): E36. 28. Agrawal A. Osteosarcoma metastasis to the orbit presenting as severe proptosis following trivial trauma. J Clin Ophthalmol Res. 2014 Sep 1;2(3):155. 29. Rajabi MT, Jafari H, Hosseini SS, Tabatabaie SZ, Rajabi MB, Amoli FA. Orbital metastasis: a rare manifestation of scapular bone osteosarcoma. J Ophthalmic Vis Res.. 2014 Oct;9(4):517. 30. Siddiqui MR, Hussain SZ, Mubarak M. Iris metastasis as the initial presentation of upper gastrointestinal tract carcinoma: a case report. J. Med. Case Rep. 2019 Dec;13(1):1-4. 31. Fishman ML, Tomaszewski MM, Kuwabara T. Malignant melanoma of the skin metastatic to the eye: frequency in autopsy series.     Arch. Ophthalmol.. 1976 Aug 1;94(8):1309-11.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareCytological Patterns of Cervical Smear Seen at Federal Medical Centre Asaba, Delta State in Nigeria English7679Anibor EseEnglish Obaroefe MartinsEnglish Jaiyeoba-Ojigho Efe JenniferEnglish Maidoh Maryjoy AneneEnglishIntroduction: The cervical smear test is the most commonly carried out cytology test for women and has been proven to help identify the emergence of cancer in the cervix. Aim: This study is aimed at evaluating various cytological patterns as well as their relationship with age. Methodology: This study employed a retrospective study design. Purposive sampling was used to collect the histological results of 82 patients seen for 4 years at the Federal Medical Centre (FMC) Asaba, Delta State in Nigeria. Ethical approval was sought from the Research and Ethics Committee of the Department of Human Anatomy and Cell Biology, Delta State University, Abraka in Nigeria. Data collected were analyzed via the Statistical Package for the Social Sciences (SPSS version 23), Chi-square test was adopted to help determine the association between observed variables. Results: Findings from this study showed patients with the ages of 31-40 years (42.7%) being the most frequently affected with cytological cervical disorders while the least was those within the ages of 41-50 years (28.0%). The preponderance of cervical smear of normal cervical lesions (61.0%) ranked the highest which was followed by Inflammatory cells (20.7%) with the least been squamous cells (1.2%). It was also evaluated from the findings that no significant association existed between age and cervical lesion patterns (p=0.732). Conclusion: From this study, it can be concluded that patients within the ages of 31-40 years of age (42.7%) have a high susceptibility to cytological cervical disorders compared to other age groups. The inflammatory cell pattern was the most commonly observed cytological disorder of the cervix while the least was squamous cell carcinoma. The pattern of cervical smear was not notably associated with the age of the patients. EnglishAsaba, Cytological, Cervical, Patterns, SmearIntroduction The cervix as an anatomical organ is made up of tissues that are primarily composed of cells; such tissues include the endocervical mucosa, a conglomerate of single-layer columnar mucous cells. These cells have the necessary amount of mucus required for lubrication of cervical walls during copulation.1 The ectocervix is also another tissue present in the cervix which consists of non-keratinized squamous epithelium which joins with the vaginal wall, this tissue helps prevent erosion of cells in the ectocervical region of the cervix. 1, 2 The cervix has fibrous tissue such as elastin (which provides the elastic properties of the cervix), collagen (which provide the structural rigidity and strength of the cervix).1  The cervix is structurally the link/passage between the uterus and vagina.2 Its neurovascular supply entails the uterine artery, uterine vein, external iliac lymph nodes and lastly the pelvic splanchnic nerve.3 It functions as a pathway for sperm entry to the uterus during copulation and also in childbirth.2 The cervix like all structures of the human body is also predisposed to abnormal cell growth of which cervical cancer is the most common condition as regards the cytological disorders of the cervix.4 Examples of such cytological disorders of the cervix are as follows: atypical glandular cell, (glandular cell of cervix deviation from the normal cytological structure/pattern of glandular cell in cervix, studies conducted by several researchers it was observed that atypical glandular cell had an incidence of 0.1-2.1% among cervical lesions),5 Atypical squamous cell, (this simply refers to inflammatory, reactive abnormal cells lining the ectocervix, they are usually associated with infections such as papillomavirus, yeast infection etc and also hormonal imbalance and benign growth of cervix. In a study conducted by Mahira and Elmir, it was observed that in an examination of 1784 female patients in Bosnia and Herzegovina only 1.7% had atypical squamous cell as a cervical cytological abnormality.6, 7 High and low grade squamous intraepithelial lesions (these refer to moderate to severe or fewer changes of cervical cells), this cytological aberration in the cervix constituted 1.3 and 1.5% in researches conducted by Mahira and Elmir also that of Tamboli respectively. 6, 8 Squamous cell carcinoma is a deviant of the normal cervical cytology which arises as a result of abnormal cell growth and changes of cervical cells such as metaplasia of cervical squamous cell, hyperplasia and abnormal production of the cervical cells. 9, 10 According to WHO, about 80% of all known cases of cervical cancer worldwide are associated with developing or low-resources countries, which can be attributed to the lack of awareness and difficulty in running cytological based screening. 11 This condition is a major health problem worldwide with a significant level of morbidity and mortality, in a recent note there has been a decline in the prevalence level of this condition in developed countries.12 Cervical Cancer ranks third (3rd) globally among female associated malignancies which are predominant in developing countries. 13 Studies have shown those below 40 years of age with the possibility of developing cervical cancer as 2%. It has also been observed that an estimate of 500,000 new cases appears each year globally, with it being the second rank most usual cause of death in the world associated with the female gender with breast cancer ranking first (1st).13 Over the years, researches have been conducted on the means and methods of identifying this condition; one of such methods is the commonly conducted Cervical smear test also known as Papanicolaou (Pap) test, a simple, non-invasive screening test conducted by examining cells of the cervix to help evaluate if there are any cytological abnormalities in the cell/tissue structure of the cervix.14 This method was introduced by George Papanicolaou in the year 1914, aimed at examining the cells of the cervix histologically to help early discovering abnormal cell development in the cervix.15 This study aimed at evaluating the various cytological patterns of cervical smear with relation to age at the Federal Medical Centre, Asaba, Delta State in Nigeria. Material and Method: Ethical Consideration: The ethical clearance used was issued by the Research and Ethics Committee Human Anatomy Department, Faculty of Basic Medical Sciences, Delta State University, Abraka. The ethical approval number is DELSU/CHS/ANA/2020/34. Study Design: The study design adopted for this research was a retrospective cross-sectional study design. Sampling Technique and Sample Size: Purposive sampling was employed for sample collection. The study population comprised 82 patients who came for cervical smear screening at the Federal Medical Centre, Asaba, Delta State, Nigeria within a period of 4 years (2016-2019). Data Collection: Data were obtained from the medical records unit of the Pathology Department, and Gynaecology Clinic registers. Data on the age of patients and cytology results of their pap smear were recorded. Data Analysis: Data were analyzed and the results were presented in tables and charts. A Chi-square test was used to evaluate the association between age and patterns of cervical smear observed with a probability acceptable at less than 0.05. Results Figure 1 showed that the most affected age group with cervical lesions are those with the ages of 31-40 years with a frequency of 42.7%, which was closely followed by those within the age group of 20-30 years with a frequency of 29.3%, the least prevalent age with this condition were those within the ages of 41-50 years of age (28.0%). Figure 2 revealed the distribution of the various patterns of cervical smear observed in the study. Normal pap smear had a frequency of 61.0%, Inflammatory pattern was the most predominant cervical lesion with a frequency of 20.7%. The rest observed patterns are arranged as follows in order of preponderance; Low-grade squamous intraepithelial lesion, High-grade squamous intraepithelial lesion, Atypical squamous cell, atypical glandular cell and the least common being Squamous cell carcinoma with their respective frequencies as follows 6.1%, 4.9%, 3.7%, 2.4% and 1.2%. Table 1 depicts that there was no significant association (p0.05) association between age and patterns of cervical smear.9, 17, 18 However, findings from studies conducted by a South African as well as Nigerians showed that age and pattern of cervical smear had a significant (pEnglishhttp://ijcrr.com/abstract.php?article_id=4140http://ijcrr.com/article_html.php?did=4140 Gray H. Gray&#39;s Anatomy (38th ed.). Churchill Livingstone; 2008, pp. 1870–73. Guyton, AC and Hall JE. Textbook of Medical Physiology (11th ed.). Philadelphia, PA: W.B. Saunders, 2005;1027. Drake RL, Vogl W and Tibbitts AWM. Gray&#39;s Anatomy for Students. Philadelphia, PA: Elsevier/Churchill Livingstone. 2005; 415, 423. Chris-Ozoko LE, Barovbe MU, Oyem JC and Ekanem VJ. 5-Year Retrospective Study of the Prevalence of Cervical Lesions at the University of Benin Teaching Hospital, Nigeria. Acta Sci Anat. 2020; 1(4): 235-243. Marques JP, Costa LB, Pinto AP, Lima AF, Duarte ME, and Barbosa AP. Atypical glandular cell and cervical cancer: Sys Rev. 2011; 57:234-8 Mahira J and Elmir J. Diagnostic Approach to patients with Atypical Squamous Cells of Undetermined Significance cytological findings on the cervix. Med Arch. 2016; 70(4):296-298. Toews HA.  The Abnormal Pap Smear:  A Rationale for Follow Up.  Can Fam Physician. 1983; 29:759-62 Tamboli GD. Accuracy of Cytological Findings in Abnormal Cervical Smear by Cyto-histological Comparison. J Med Edu Res. 2013; 3(2):19-24. Pushp LS, Meenakshi S, Munna LP, and Rekha S. A Study on Cervical Cancer Screening Using Pap Smear Test and Clinical Correlation. Asia Pac J Oncol Nurs. 2018; 5:337-41. Patel MM, Pandya AN, and Modi J. Cervical Pap Smear Study and its Utility in Cancer Screening, to Specify the Strategy for Cervical Cancer Control.  Natl J Community Med. 2011; 2:49?51. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C and Rebelo M. Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136:359?86. Juneja, A., Sehgal, A., Sharma, S.and Pandey, A. Cervical Cancer Screening in India:  Strategies Revisited.  Indian J Med Sci. 2007; 61:34-47. Gyawali B, Keeling JJ, Teijlingen E, Dhakal L and Aro AR. Cervical Cancer Screening in Nepal: Ethical Considerations. Medico-legal Bioethics. 2015; 1-4. Bangalore NR and Arshiya S. Cytopathological Study of Cervical Smear: A Hospital-Based Retrospective Study. Med J Islamic World Aca of Sci. 2014; 22(1): 42-49. Padubidri V and Daftary SN. Gynaecological Diagnosis. In:  Howkins and Bourne Shaw’s textbook of Gynecology.  13th ed.  Noida:  Elsevier India Private Ltd; 2004; 77-187. Pragya GG, Durga BCR, Kavita S, Kamar J. and Richa S. Spectrum of Cytological Patterns in Cervical PAP Smears in a Tertiary Care Center of Western Region of Nepal. Nepal J Med Sci. 2019; 4 (1): 2-8. Adepiti CA, Ajenifuja KO, Okunola O, Omoniyi-Esan GO. and Uche O. Age and Pattern of Pap smear Abnormalities: Implications for Cervical Cancer Control in a Developing Country. J Cytol; 2017; 34 (4): 208-211. Fadwa JA. Cervical Cancer Screening with Pattern of Pap Smear. Review of Multicenter Studies. Saudi Med J. 2006; 27 (10): 1498-1502. Bhagya LA, Prasad UMS. and Satish K. Cytological Patterns of Cervical Pap Smear with Histopathological Correlation. Int J Res Med Sci. 2015; 3 (8): 1911-1916. Missaoui N, Trabelsi A, Landolsi H, Jaidaine L, Mokni M. and Korbi S.  Cervical adenocarcinoma and squamous cell carcinoma incidence trends among Tunisian women.  Asian Pac J Cancer Prev. 2010; 11:777?780. Mohammed A, Ahmed SA, Oluwole OP. and Avidime S. Malignant tumours of the female genital tract in Zaria, Nigeria. Ann Afr Med. 2006; 5:93?96. Babarinsa A, Akang EE. and Adewole IF Pattern of gynaecological malignancies at the Ibadan cancer registry (1976?1995). Nig Q J Hosp Med.; 1998, 8:103?106. Denny L. Cervical Cancer: Prevention and Treatment. Discov Med. 2012; 14(75):125-31. Mosuro AO, Ajayi I, Ademola AO, Adeniji OA and Oluwasola O. Prevalence of Cervical Dysplasia and associated Risk factors among women presenting at a primary care clinic in Nigeria. J of Basic & Clin Rep Sci. 2017; 4(2): 70-79.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareEnrichment of Remote Homology Detection using Cascading Maximum Entropy Markov Model English8084Manikandan PEnglish Ramyachitra DEnglish Muthu CEnglish Sajithra NEnglishIntroduction: In computational biology, the remote homology detection of the protein sequence is one of the ultimate problems that aims to discover the protein sequences from the database of known protein structures that are evolutionarily associated with a known query protein. Protein homology detection plays a major role in predicting the structures and functions of the protein. Sequence and structure-based comparison allow to detection of the remote homologous. Aim: Several existing computational techniques have been developed to predict remote homology detection in protein sequences. Due to low similarities in protein sequence, the performance of the existing systems is still low. To overcome the drawbacks of the existing systems, this research work proposed a Cascading Maximum Entropy Markov Model (C-MEMM) for remote homology detection. Methodology: The C-MEMM algorithm improved freedom in selecting features to signify the annotations for sequence tagging methods rather than Hidden Markov Model (HMMs). In sequence tagging circumstances, it is valuable to practice domain knowledge to project special-purpose features. The proposed C- MEMM algorithm allows the user to specify lots of correlated, but informative features. Results: Three different organisms such as Xenopus laevis, Bacillus stearothermophilus and Escherichia coli were used for testing the execution of the C- MEMM algorithm with the existing methods. The effectiveness of the proposed C-MEMM algorithm is tested with Coverage and Precision values. Experimental results show that the proposed method effectively improved prediction performance. Conclusion: From the experimental results, it is inferred that the proposed C-MEMM algorithm gives better results than the existing algorithms based on the performance metrics such as coverage rate and precision values for all the organisms. EnglishProtein remote homology detection, Cascading Maximum Entropy Markov Model (C-MEMM), Position-Specific Iterated BLAST (PSI-BLAST), Cascade-HMM (C-HMM), Structural Classification of Proteins (SCOP), Xenopus Laevis, Bacillus Stearothermophilus, Escherichia ColiIntroduction Genome sequence projects provide a huge number of protein sequence data in several databases. The volume of inconsistency among the sum of known protein sequence and the sum of experimentally determined protein structures has been rapidly improved due to the experimental obstacles in analyzing the protein structures and functions. To overcome the limitations, a huge number of computational tools and methodologies have been developed to analyze the protein structure and functions employing the sequence information offered in open-source repositories. If two proteins share evolutionary origins and having more similarities are termed as homolog proteins.  Earlier methods in protein homology detection can be clustered into three categories such as pairwise, discriminative and generative methods. Dynamic programming is used in pairwise methods to perform sequence similarity for homology detection.1 Dynamic programming method consumes more computation times for relatively long protein sequences. To accelerate the alignment, a heuristic method named Basic Local Alignment Search Tool (BLAST)2 is used to find a near-optimal alignment within a rational period. The general hypothesis is that two proteins sequence identity is above 30% over their entire lengths is termed as homolog.3 The disadvantage of pairwise sequence alignment is biological erroneousness of assessment concerning only one identified protein homolog. Several iterative techniques such as PSI-BLAST, SAM-T98have been developed to overcome the drawbacks of pairwise methods.4,5 However, the generative methods also produce so much false-positive results. Hence, the recent studies on remote homology detection used discriminative methods to make separation among homolog and non-homolog proteins. Remote homology detection of protein sequence plays a crucial role in the field of computational biology because remote homologous proteins contributing similar functions and structures that can be helpful in the protein studies of 3D structure and function.6 The remaining section of this manuscript is developed as follows: Section 2 designates the background study of existing methods for solving the problem of remote homology detection. The methodology of the proposed C-MEMM algorithm is explained in Section 3. The experimental outcomes of the proposed and the existing algorithms for the Structural Classification of Proteins (SCOP) database is emphasized in Section 4. Lastly, Section 5 spotlights the conclusion and future enhancement.  Background Study      ­­­       Genome sequence projects generate a huge amount of sequence information and it needs to be annotated. Most of the homology detection methods use the scoring metric to predict the similarity among a query protein with the database sequences. The Smith-Waterman score is frequently used for comparing two protein sequences. In Bioinformatics, the structural and functional annotation of an unknown protein is a crucial task. The annotation of a new protein sequence is based on the similarity among the query protein with the structures and function of the known protein.             If such protein relationship cannot be identified using direct sequence-based approaches, it can be termed as remote homologues and the discovery of remote homologue relationship is a difficult task in computational biology. In several cases, the functional annotation for the new proteins can be done using the protein structures. But the information of protein structures is inadequate and the structure database is also very deliberate.7 Hence, there is a need to find distant homologues by abusing protein sequence information. Several techniques have been developed to identify the homologue sequences grounded on profile Hidden Markov Models (HMM) and Position-Specific Scoring Matrices (PSSM). The probabilistic model-based profile Hidden Markov Models are further complex in detecting the remote homologue proteins. 4,8,9 HHblits and HH search are used to find the remote homologues by the HMM-HMM comparison.10,11 The Cascading PSI-BLAST method cover more distant relationships, but the major drawback of this method is computational time, which increases the size and complexity of the databases.12,13 Pcons delivers improved automated tools for the prediction of protein structure and analysis of this structure using consensus.14 The difficult target protein sequence is robotically submitted to open-source servers of fold recognition to find distant structural homologies. Inside the kernel formulation background, the consensus method is used to merge heterogeneous data by semidefinite, second-order cone, semi-infinite linear programming and Bayesian framework.15 These kernel learning methods are not scalable and guide to very complex frameworks. The Motifs pattern of protein sequence represents highly conserved regions of proteins. The motif content of two protein sequences is used to express a similarity among them. On completion of motifs, significant hints to a protein function can habitually be exposed even if it is not universally similar to any known protein in sequence databases. In consequence, the motif method suits well in remote homology detection and emphasis conserved segments of sequence having more similarity in the vaguely related protein sequence.16 An enhancement in protein remote homology detection is accomplished by emerging techniques grounded on the profile-sequence comparison.17 The profile is typically constructed from the query protein sequence or directly from an input multiple sequence alignment.          SAM - T04 approach used Neural Networks (NNs) to evaluate the alignment and map the similarities among pairs of proteins.18 The main improvements made by the human intervention were from adding constraints to build beta-sheets and from splitting multi-domain proteins into separate domains. Support Vector Machines (SVM) are mainly used to resolve the problem of binary classification. The support vector machine technique builds one-versus-rest classification models. These models are assessed with esteem to how well each binary classifier can identify the proteins that fit its own modelled class.19 Long Short - Term Memory (LSTM) is a moderately quicker approach than using alignments and SVM based models. The LSTM is a recurrent NN method that can be used for remote homology detection by determining the discriminating patterns.20 However, this technique does not attain comparable performance. The Cascade-Hidden Markov Model (C-HMM) involves cascading of HMM to identify the true distant homologues at various levels.14 The execution time of cascade searches are higher than the other existing methods. Even though several methods have been developed for predicting the remote homologues proteins, but they do not promise to provide better results. Hence, the C-MEMM algorithm has been developed in this research work to overcome the drawbacks of the existing methods.    Methodology             In this research, the existing algorithms, namely PSI-BLAST, C-HMM and the proposed C-MEMM algorithms are compared to predict the remote homology detection. From the results, it is inferred that the C-MEMM method provides improved results than the existing algorithms.             Drawing stronger links will be equally valuable for both areas of research is the key motive of Cascading Maximum Entropy Markov Models (C-MEMM) model. Markov models are used for both prediction and estimation, where the states of sequence produce a consistent sequence of annotations. In the maximum entropy method, the annotations are self-determining is also known as logistic regression. Hence, the Maximum Entropy Markov Model can be obtained from logistic regression through an assumption of Markovian between target variables.             In general, the Maximum Entropy Markov Models (MEMM) algorithm is measured by forwarding pass in separation. In HMMs, the backward pass is no longer candid. MEMM algorithm is very efficient, but they grieve from the problem of label bias, where a feeble probability reduces the probability of inactivity across time. To overcome the problem label bias, the linear chain Conditional Random Fields (CRFs) are used. Classifier Chain (CC) is a Cascading MEMM and it can be observed as a T order MEMM. Several existing multi-label methods already split the sequence into subsets.             An associated method is developed in this research work which furthermore links the blocks together, this data is not separated. Most of the existing multi-label techniques are previously transformed the datasets earlier working on them. The same flow of C-HMM is used in C-MEMM, only the Hidden Markov Model (HMM) is replaced with MEMM. All the modules Cluster-MEMM, Cascade MEMM and Custom MEMM are used to classify remote homologues proteins from the sequence databases. The key inspiration of developing the C-MEMM method is to authorize effective detection of remote homology compared to any accessible sequence database, regardless of its dimensions.             C-MEMM algorithm includes cascading of MEMMs by numerous generations to identify true distant remote homologues at various levels such as superfamily and fold. Every true hit of the first group is measured as query sequences to instigate the second group of C-MEMM. Cluster-HMM Module clusters the collected homologues (hits) while penetrating against such enormous databases. Custom-MEMM filter hits gained from the first group are clustered at a specific sequence identity cut-off by Cd-hit. This technique further diminishes the search time without remarkable loss in sequence information in contrast with the two existing modules. Results and Discussion             In this research work, the proposed algorithm is tested with the well-known benchmark dataset named SCOP 1.53 for analyzing the performance of the algorithm based on its effectiveness. The proposed C-MEMM algorithm has been assessed by comparing with two existing techniques, namely PSI-BLAST and C-HMM.  Dataset Description             The SCOP 1.53 database has been used as a standard database for remote homology detection.  The datasets are retrieved in FASTA format from the ASTRAL compendium for sequence and structure analysis. The SCOP 1.53 database comprises 4352 protein sequences gathered into seventy-four families and fifty-four superfamilies. The dataset was further reduced into 1294 protein sequences which is gathered into forty-six families, one hundred fifty-five superfamilies and two hundred sixty-five folds. The protein domains inside the family are taken as test instances and protein domains inside and outside the superfamily are taken as training positive instances. This produces fifty-four families with ten training and five test positive instances. The negative instances of the protein family are selected via the exterior of the positive sequences fold and were stochastically divided into training tests and test sets in a similar ratio as the positive example. Performance Measures             The execution of PSI-BLAST, C-HMM and C-MEMM algorithm is assessed by the performance metrics such as coverage and precision values. The coverage is termed as the true positives acknowledged by the method of sequence search via the total amount of true associations extant in the database at various levels namely family, superfamily and fold (Eq.1).                 The false-positive can be term as, “any hit that did not belong to the same fold as query sequence”. Precision scores are used to detect the fraction of hits that are related to the sequence search (Eq.2).                                        where TP and FP stand for the number of True Positives and False Positives which are recognized through sequence searches. Experimental Results The Scop 1.53 database is used for testing the performance of the proposed C-MEMM algorithm with the existing algorithms namely PSI-BLAST and C-HMM. The comparison of performance measures such as coverage and precision for the existing and the proposed algorithms are shown in Table 1. Fig.1 shows the comparison of Coverage for the proposed and the existing algorithm such as PSI-BLAST and C-HMM. From Fig.1, it is inferred that the C-MEMM algorithm performs better than the other existing techniques in terms of Coverage values. Fig.2 shows the comparison of precision values for the proposed C-MEMM algorithm with the other existing algorithms. From Fig,2, it is inferred that the proposed C-MEMM algorithm provides better results compared to existing PSI-BLAST, C-HMM approaches. For the coverage values in Fig.1, it is inferred that the proposed C-MEMM algorithm performs 24.78 % better than the PSI-BLAST algorithm and 9.65% better than the C-HMM algorithm for the Frog organism.             For the Bacillus stearothermophilus organism, it is inferred that the proposed C-MEMM algorithm performs 73.29% better than the PSI-BLAST algorithm and 15.15% better than the C-HMM algorithm. For the Escherichia Coli organism, it is inferred that the proposed C-MEMM algorithm performs 82.29 % better than the PSI-BLAST algorithm and 9.16% better than the C-HMM algorithm. For the precision values in Fig.2, it is inferred that the proposed C-MEMM algorithm performs 31.94 % better than the PSI-BLAST algorithm and 12.58% better than the C-HMM algorithm for the Frog organism. For the Bacillus stearothermophilus organism, it is inferred that the proposed C-MEMM algorithm performs 65.29% better than the PSI-BLAST algorithm and 28.79% better than the C-HMM algorithm. For the Escherichia Coli organism, it is inferred that the proposed C-MEMM algorithm performs 71.47% better than the PSI-BLAST algorithm and 51.99% better than the C-HMM algorithm. 5. Conclusion and Future Enhancement             Remote homology detection is one of the crucial tasks for detecting homology in low sequence similarity cases. The discriminative method has classified the proteins using the sequences that must be transformed into fixed-length feature vectors. In this research work, the C-MEMM model was successfully implemented to detect protein remote ho­mologies. When the C-MEMM method was applied to the feature data set, the sequence re­turned a prediction score of every instance. The effectiveness of the proposed approach is tested with Coverage and Precision values. Experimental results show that the proposed method effectively improved prediction performance. In future, this research work can be enhanced to discover novel features of protein sequences and applying other language processing methods for the detection of protein remote homology. Acknowledgement             The authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Conflict of Interest The authors declare that they have no conflict of interest. Source of Funding: NIL Author’s Contribution Dr Manikandan P: Manuscript Preparation Dr Ramyachitra D: Manuscript Editing Dr Muthu C: Manuscript Reviewing Ms Sajithra N: Literature Review Englishhttp://ijcrr.com/abstract.php?article_id=4141http://ijcrr.com/article_html.php?did=4141 Smith TF, Waterman MS. Identification of common molecular subsequences. J. Mol. Biol.. 1981 Mar 25;147(1):195-7. doi: 10.1016/0022-2836(81)90087-5. PMID: 7265238. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J. Mol. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareNomophobic Rate of Higher Secondary Level Students - A Pilot Study English8589Elias JijishEnglish Mirunalini MEnglishIntroduction: In the context of the lockdown due to Covid-19, usage of mobile phones has increased among adolescents. Usage of mobile phones for educational purposes as well as for entertainment makes them more addicted to mobile phones and electronic gadgets. In this scenario, Nomophobia, which is fear towards the situation when there is no phone, has increased among the adolescent. Aim: This research study aimed to prepare a nomophobic rating scale (NPRS) for adolescents and to implement it for students at the Higher secondary levels to check their nomophobic rate. Methods: In this study, investigators developed and standardized a Nomophobic rating scale to identify the addiction rate of Higher Secondary school students to mobile phones. Nomophobic Rating Scale was applied to 92 Higher Secondary Level students in Kerala and the collected data analyzed for evaluation. Results: The study shows that most of the students are prevalent to nomophobia. But the nomophobic rate does not depend on their locality, gender, course stream, but depend on the management of the school. Conclusion: This study points out certain serious concerns regarding the necessity of proper monitoring among adolescents about their usage of mobile phones. It also highlights the necessity of timely interventions on the part of teachers, parents and professionals which will invariably enhance the physical, social and emotional development of the students at the higher secondary level. EnglishNomophobia, Nomophobic rate, Mobile phone, Higher secondary level, Students, Nomophobic rating scaleINTRODUCTION             The pandemic situation increased the usage of technology as well as mobile phones in the nook and cranny of life. It had a huge impact on the teaching and learning process too. In the context of COVID-19 teaching-learning strategies had changed a lot and a predominant role goes to the usage of mobile phones and social media among students as well as teachers. Even before the widespread of COVID -19, adolescent students had a high affinity towards modern gadgets like smartphones to play online games and use various social media applications. This affinity towards smartphones coined a new term among psychologists, which is known as nomophobia.             The term NOMOPHOBIA or NO Mobile Phone PhoBIA is used to describe a specific psychological condition when people have a fear of being detached from their mobile phone connectivity.1 Nowadays nomophobia has become a psycho-social condition because the socialization process is carried out through social media and most people have access to social media through their smartphones.             The usage of mobile phones and other electronic gadgets were not much motivated by the parents of higher secondary school students who are in their adolescent stage of development. Some studies regarding the usage of mobile phones and social media were conducted by researchers in the eastern countries but they haven’t concentrated on adolescent students much.2 In the Indian situation, there were very few studies conducted by researchers in the field of nomophobia. Lack of usage of mobile phones among the students was the main reason for that. But the pandemic situation increased the usage of mobile phones among the students and the continuous usage lead to a kind of addiction towards mobile phones. This makes the study more relevant and the needs of the current era and this makes the suitability to fill the research gap.             Mobile phones and similar electronic gadgets became part and parcel of everyone’s life, especially among adolescents and youngsters. Internet facilities are available at every village at a very cheap and affordable cost. Every smartphone is connected to the internet through 4G or higher band connectivity. Speed of data transfer and communication increased at a very high rate. Most of the people are active on any of the social media platforms. All these things made people show more affinity towards smartphones.             Usage of mobile phones for educational purposes as well as for entertainment makes them more addicted to mobile phones and electronic gadgets.3,4 In this scenario, Nomophobia, has increased among adolescent. Sufficient studies on this field, especially in India were very few. So the study has its importance in the current situation. REVIEW OF RELATED LITERATURE             A cross-sectional study among undergraduate students who were using mobile phones for more than one year found that phone dependence among undergraduate students was common and there was no difference between the male and female students. Shankar, V., Singh, K., & Jangir, M.K.(2018) found 40.93 percentages of addiction and the study also showed that females were more addicted to mobile phones than males.5  A study on the perception among College Students by  Gnanadhas J, Venkatachalam J, Menon V and Olickal J in Puducherry about nomophobia found that a sizeable minority of the students showed signs of severe nomophobia, distinct patterns of usage, and misperceptions regarding health and their usage pattern .6             The study conducted among undergraduate medical students from India in 2019 by Myakal & Vedpathak concluded that 71.4 % of them were prevalent to nomophobia. The study also concluded that male students are more addicted to mobile phones.7 Another study suggested a high prevalence of smartphone addiction among medical students, particularly in male medical students.8 A study by Ahmed, Pokhrel, Roy & Samuel among students pursuing physiotherapy course has been established that there is a relation between nomophobia rate and academic performance.9 In a study conducted by Muralidhar et al. in Kerala, a great prevalence of nomophobia was found among medical college students. According to the study, the rate of nomophobia was not found to be associated with their sex admission type, place of birth, and place of their stay.10 The results of the study by Yasan & Yildirim showed that undergraduate students had an average nomophobia level and they used their mobile phones for several educational purposes.11 The students’ level of nomophobia was significantly related to educational activities done by mobile phones. A study by Gonçalves et al., 2020 analyzed the propensity of young adults (18–24 years old) towards nomophobia and lifestyle.12 Aguilera-Manrique et al., 2018 studied nursing students&#39; clinical practicum and found that there was a connection between nomophobia and the distraction caused by smartphone use. They concluded from the study that nursing students with high levels of nomophobia often use their smartphones during clinical practicum, while they also agree that regulations limiting smartphone usage while working should be implemented.13 Cerda-Flores et al. carried out a transverse-analytical study among 200 nursing university students. The instrument “Are you a nomophobic?” was applied. The frequencies obtained from men and women showed high heterogeneity.14 The study of Prasad et al (2017) discovered about 39.5% of students agreed that they score low marks in professional exams if they spend more time on the phone.15Most of the study concluded that academic achievement of students affected negatively by nomophobia and such studies on adolescent higher secondary school students were not done effectively, especially in India.  NEED AND SIGNIFICANCE OF THE STUDY             A review of related literature shows that several studies have been conducted in the field of nomophobia by several researchers at different levels, especially among undergraduate and medical students. But mobile phone usage of secondary or higher secondary school students was not investigated in detail by any of the studies, especially from India.16  The main reason behind the negligence of that age group is that they didn’t possess a mobile phone. But when the pandemic situation necessitated an academic ambience where the mobile phone was indispensable, most parents were forced to purchase it for their wards. The study is conducted at the time when one year is over after the first COVID -19 case was reported in the world and so seems significant for the current context.             The usage of smartphones became a part of each student at a higher secondary level because the teaching-learning process moved from the traditional ways to online mode by using plenty of online platforms. Teachers who are well versed with technology and the internet shifted to google classrooms, google meets and zoom meets while others depended on what&#39;s app and youtube channels. Whatever be the mode of teaching and platform used by the teacher, students are forced to use their smartphones for learning purposes. But while using smartphone for learning purposes, there is a chance of deviation from the academic usage of the phones to something else. The other purposes including the usage of phones for using social media platforms for communication and watching entertainment videos and songs. Thus the investigators believe that a study on nomophobia rate of higher secondary school students would be the need of the present.  RESEARCH OBJECTIVES  The general objective of this research was to study the nomophobic rate among Higher Secondary school students. The specific objectives were; To develop and standardize a nomophobic rating scale. To determine the Nomophobic rate of Higher secondary school students. To establish the relation between demographic factors and nomophobic rate. METHODS Research design A descriptive research design was followed by the investigators for the current study. This pilot study was conducted in one government and one aided higher secondary school in the Palakkad district of Kerala. The participants of this study consisted of students who were enrolled in the second year of higher secondary courses.  Instrument of the study A nomophobic rating scale developed and standardized by the investigators was used for the present study. The nomophobic rating scale for Higher Secondary Level Students was a Likert type 5 point scale developed through three stages. In the pre-try-out stage, investigators formulated 46 statements from the ideas gained from the review of related literature and the statements were validated by experts in the field. After that, it was tried out to selected a sample and finalized to 26 items with 6 negatively polar statements. Data collection and data analysis          After the standardization of tools, a pilot study was conducted among 92 higher secondary school students. For the pilot study, the NPRS shared with Higher Secondary School students who were indifferent streams of study through WhatsApp groups of their respective schools and 92 responses were collected through Google form. The collected responses were exported as a google sheet and transformed into scores as per the scoring key.  Students to test and one-way ANOVA was used to compare the means of nomophobic rate concerning each independent variable, namely, gender, stream, of course, management of school and locality of the student. Significance of difference between the mean values of nomophobic rate concerning the gender, locality of students and management of the school was analyzed using t-test while Significance of difference between the mean values of nomophobic rate concerning a stream, of course, analyzed using one-way ANOVA test. The mean value of nomophobic rate of HSS students was 79.23 and have positive skewness. The ethical clearance number for this study was  No. 16872/Ph D K7/ Education/part Time January 2018 dated 28.12.2017. From table 1, it is clear that the male and female students, as well as students from rural and urban areas, do not have any significant difference concerning their nomophobic rate. But nomophobic rate is significantly different among government and aided school students. One way ANOVA test depicted in table 2 shows that there is no significant difference between science, commerce and humanities students concerning their nomophobic rate. RESULTS AND DISCUSSION             The NPRS was constructed and standardized according to the standard techniques for the standardization of a Likert-type scale with a five-point rating scale. It contains 24 items among 7 of them are negatively polar and the rest were positively polar. The maximum score which can be obtained by a sample is 120 and the minimum score is 24. If the sample is 100% neutral to the statement, the score will be 72. If a sample gains a score below 72, then it means that the sample is moderately or less nomophobic while a score that is higher than 72 shows that the sample is more addicted to the gadgets. As the score reaches 120, the sample needs adequate attention and may be requested for an intervention from a professional for retrieval from the symptoms.             The data collected and analyzed shows a mean value of 79.23 for nomophobic rate. This mean value tells that most of the students are prevalent to nomophobia. Male and female students as well as students from rural and urban areas do not have any significant difference concerning their nomophobic rate. But nomophobic rate is significantly different among government and aided school students. So the nomophobic rate does not depend on their locality, gender, course stream but depends on the management of the school. Conclusion             Technology is a boon when it is used productively. In the age of digital natives, the creative usage of mobile phones can never be ruled out. During the contemporary scenario when the entire world faces an unprecedented standstill, mobile phones play a pivotal role in carrying out academic activities by teachers and students throughout the globe. Even after the threat of this pandemic vanishes, the academic community will undoubtedly move forward in tune with the technological advancements in the years to come. Still, this study points out certain serious concerns regarding the necessity of proper monitoring among adolescents concerning their usage of mobile phones. It also highlights the necessity of timely interventions on the part of teachers, parents and professionals which will invariably enhance the physical, social and emotional development of the students at the higher secondary level. ACKNOWLEDGMENT The authors would like to thank the authorities of the Department of Educational Technology Bharathidasan University, Tiruchirappalli and various school authorities who helped during data collection. Conflict of interest and source of Funding Nil  Author Contributions Elias, Jijish designed and formulated research goals and objectives as a whole. After discussion with Mirunalini, M both determined the right method and designed the study model. Elias, Jijish prepared the tool and validated it with the help of Mirunalini. Data for the pilot study was collected by Elias, Jijish and analyzed under the supervision of Mirunalini, M. Both critically revised the manuscript and all authors had approved the final version Englishhttp://ijcrr.com/abstract.php?article_id=4142http://ijcrr.com/article_html.php?did=4142 King AL, Valença AM, Nardi AE. Nomophobia: the mobile phone in panic disorder with agoraphobia: reducing phobias or worsening of dependence?. Cogn Behav Neurol. 2010;23(1):52-4. Beranuy M, Oberst U, Carbonell X, Chamarro A. Problematic Internet and mobile phone use and clinical symptoms in college students: the role of emotional intelligence. Comput Hum Behav. 2009;25(5):1182–1187.   Daei A, Ashrafi-Rizi H, Soleymani MR. Nomophobia and Health Hazards: Smartphone Use and Addiction Among University Students. Int J Prev Med.2019:10(1):202. Thapa K, Lama S, Pokharel R, Sigdel R, Rimal SP. Mobile Phone Dependence among Undergraduate Students of a Medical College of Eastern Nepal: A Descriptive Cross-sectional Study. J Nepal Med Assoc.2020:58(224):234-239 Shankar V, Singh K, Jangir M. NOMOPHOBIA: Detection and Analysis of Smartphone Addiction in Indian Perspective.Int J Appl Eng Res. 2018 [cited 7 January 2021];13(14):11593-11599. Available from: https://www.ripublication.com/ijaer18/ijaerv13n14_36.pdf  Gnanadhas J, Venkatachalam J, Menon V, Olickal J. Nomophobia: A Mixed-Methods Study on Prevalence, Associated Factors, and Perception among College Students in Puducherry, India. Indian J Psychol Med . 2019;41:541-548. Myakal VV, Vedpathak VL. Nomophobia - mobile phone dependence, a study among students of a rural medical college. Int J Community Med Public Health. 2019;6(5):2034–2040. Lei LY-C, Ismail MA-A, Mohammad JA-M, Yusoff MS. The relationship of smartphone addiction with psychological distress and neuroticism among university medical students. BMC Psych. 2020;8(1). Ahmed S, Pokhrel N, Roy S, Samuel AJ. Impact of nomophobia: A non-drug addiction among students of physiotherapy course using an online cross-sectional survey. Ind J Psych. 2019;61(1):77-80. Madhusudan M, Sudarshan BP, Sanjay TV, Gopi A, Fernandes SDA. Nomophobia and determinants among the students of a medical college in Kerala. Int J Med Sci Public Heal. 2017;6(6):1046-1049. . Yasan KN, Yildirim S. Nomophobia omophobia among undergraduate students and its link to mobile learning. 10th International Conference on Education and New Learning Technologies Project: Nomophobia. 2018. p.3018-3025. Gonçalves S, Dias P, Correia A-P. Nomophobia and lifestyle: Smartphone use and its relationship to psychopathologies. Computers in Human Behavior Reports. 2020;2:100025. Aguilera-Manrique G, Márquez-Hernández VV, Alcaraz-Córdoba T, Granados-Gámez G, Gutiérrez-Puertas V, Gutiérrez-Puertas L. The relationship between nomophobia and the distraction associated with smartphone use among nursing students in their clinical practicum. PLOS ONE. 2018;13(8). Cerda-Flores R, Martinez-Hernandez R, Tamez-Rodríguez V, Treviño-Sordia V, Hernandez-Saldaña M. Nomophobia in Mexican Nursing Students. Revista Medicina de Torreón. 2018;10(1):44–7. Prasad M, Patthi B, Singla A, Gupta R, Saha S, Kumar JK, et al. Nomophobia: A Cross-sectional Study to Assess Mobile Phone Usage Among Dental Students. J. Clin. Diagnostic Res. 2017;11(2): ZC34–ZC39. Kanmani A, Bhavani U, Maragatham R . NOMOPHOBIA – An Insight into its Psychological Aspects in India, Int. J. Indian Psychol.2017:4(2):5-15.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcarePrevalence of Testosterone Hormone Deficiency and its the Correlation with Other Clinical Parameters in (Chronic Kidney Disease) CKD Patients on Hemodialysis English9093Chaudhary Vinit RameshEnglish Gharge Sushilkumar SunilEnglishIntroduction: Chronic kidney disease (CKD) is a wide range of metabolic alterations and hormonal disorders leading to endocrine dysfunctions often leads to worse outcomes. One such abnormality is a variable degree of hypogonadism and androgen deficiency. Aim: The present study aim was to study the CKD Patients. Methods: This observational study was conducted on a cohort of 50 CKD patients from June 2020 to July 2020. All clinically stable patients for the last six months and on hemodialysis were included. Results: This observational study consisting of 50 CKD patients with 30 (60%) of them in stage 5, 17 (34%) of them in stage 4, and 3 (6%) of them in stage 3 CKD. Testosterone deficiency was found in 32 (64%) patients. Conclusion: Testosterone is inversely associated with CKD stages, blood urea levels, creatinine is positively associated with haemoglobin level and duration of dialysis. EnglishTestosterone hormone deficiency, CKD patients, Hemodialysis, Haemoglobin level, Renal, Endocrine dysfunction, HypogonadismIntroduction: One of the common features among renal patients especially chronic kidney disease (CKD) is a wide range of metabolic alterations and hormonal disorders leading to endocrine dysfunctions. 1These are often associated with worse outcomes. One such abnormality is a variable degree of hypogonadism and androgen deficiency. Testosterone deficiency has been reported to be present in 26-66% of patients with CKD.2 Androgen deficiency leads to abnormal spermatogenesis, steroidogenesis, erectile dysfunction, decreased libido, and infertility. 3 It has been observed that deterioration of renal function leading to sexual dysfunction is not correctable by even dialysis. Sometimes, they deteriorate and male patients who are on dialysis can become impotent too. 4 Studies have proven that low levels of testosterone have led to many other changes in the body like anaemia, cognitive impairment, cardiovascular disease, and increased mortality. 1,5,6,7 This study was conducted to build on the previous evidence in the Indian scenario. By this study, we aim to estimate the prevalence of testosterone hormone deficiency and its correlation with other clinical parameters in a cohort of CKD patients on hemodialysis at our institute which is a tertiary care centre in the southern part of Maharashtra state. Methods: This observational study was conducted on a cohort of 50 CKD patients from June 2020 to July 2020. All clinically stable patients for the last six months and on hemodialysis were included. Endogenous testosterone level, hemoglobin, urea, creatinine, electrolytes (sodium and potassium), total proteins, albumin, and globulin levels were measured. Written informed consent was taken from all patients. Data entry and analysis was done in SPSS version 22.0 (IBM). Statistical significance was considered with a     p < 0.05. An independent sample t-test was used to determine the difference between laboratory parameters in testosterone deficient and normal groups. Pearson’s correlation coefficient and scatter plots were used to determine the relationship between testosterone levels and other clinical parameters as well as the duration of dialysis. Results: This observational study consisting of 50 CKD patients with 30 (60%) of them in stage 5, 17 (34%) of them in stage 4, and 3 (6%) of them in stage 3 CKD. The description of the study participants is given in Table 1. The mean age of participants in our study was 47.36 ± 14.44 years. Testosterone deficiency was found in 32 (64%) patients. The mean testosterone level was 267.22 ± 152.54 mg/dl. In the testosterone deficient group, it was 174.62 ± 87.42 and in the testosterone normal group it was 431.84 ± 91.09 mg/dl. On applying, independent sample t-test, there was a significant difference in the laboratory parameters like haemoglobin (pEnglishhttp://ijcrr.com/abstract.php?article_id=4143http://ijcrr.com/article_html.php?did=41431. Carrero JJ, Qureshi AR, Nakashima A, Arver S, Parini P, Lindholm B, Bárány P, Heimbürger O, Stenvinkel P. Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrology Dialysis Transplantation. 2011 Jan 1;26(1):184-90. 2. Iglesias P, Carrero JJ, Díez JJ. Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.  J. Nephrol.. 2012 Feb;25(1):31. 3. Swerdloff RS, Wang C. Three-year follow-up of androgen treatment in hypogonadal men: preliminary report with testosterone gel. The ageing male. 2003 Jan 1;6(3):207-11. 4. Sherman FP. Impotence in patients with chronic renal failure on dialysis: its frequency and aetiology. Fertility and sterility. 1975 Mar 1;26(3):221-3. 5. Bain J. Testosterone and the ageing male: to treat or not to treat?. Maturitas. 2010 May 1;66(1):16-22. 6. Jones TH. Testosterone deficiency: a risk factor for cardiovascular disease?. Trends in Endocrinology & Metabolism. 2010 Aug 1;21(8):496-503. 7. Carrero JJ, Stenvinkel P. The vulnerable man: impact of testosterone deficiency on the uraemic phenotype. Nephrology Dialysis Transplantation. 2012 Nov 1;27(11):4030-41. 8. Bello AK, Stenvinkel P, Lin M, Hemmelgarn B, Thadhani R, Klarenbach S, Chan C, Zimmerman D, Cembrowski G, Strippoli G, Carrero JJ. Serum testosterone levels and clinical outcomes in male hemodialysis patients. Am. J. Kidney Dis.2014 Feb 1;63(2):268-75. 9. Kyriazis J, Tzanakis I, Stylianou K, Katsipi I, Moisiadis D, Papadaki A, Mavroeidi V, Kagia S, Karkavitsas N, Daphnis E. Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients. Nephrol Dialysis Transpl. 2011 Sep 1;26(9):2971-7. 10. Albaaj F, Sivalingham M, Haynes P, McKinnon G, Foley RN, Waldek S, O’donoghue DJ, Kalra PA. Prevalence of hypogonadism in male patients with renal failure. Postgrad. Med J. 2006 Oct 1;82(972):693-6. 11. Gungor O, Kircelli F, Carrero JJ, Asci G, Toz H, Tatar E, Hur E, Sever MS, Arinsoy T, Ok E. Endogenous testosterone and mortality in male hemodialysis patients: is it the result of ageing?. Clin J Am Soc. Nephrol.. 2010 Nov 1;5(11):2018-23. 12. Ekart R, Taskovska M, Hojs N, Bevc S, Hojs R. Testosterone and haemoglobin in hemodialysis male and female patients. Artificial Organs. 2014 Jul;38(7):598-603. 13. Cigarrán S, Coronel F, Florit E, Calviño J, Villa J, Tabares LG, Herrero JA, Carrero JJ. Testosterone deficiency in dialysis patients: Differences according to the dialysis techniques. Nefrología (English Edition). 2017 Sep 1;37(5):526-30. 14. Dhindsa S, Reddy A, Karam JS, Bilkis S, Chaurasia A, Mehta A, Raja KP, Batra M, Dandona P. Prevalence of subnormal testosterone concentrations in men with type 2 diabetes and chronic kidney disease. Eur J Endocrinol. 2015 Sep 1;173(3):359-66. 15. Khurana KK, Navaneethan SD, Arrigain S, Schold JD, Nally Jr JV, Shoskes DA. Serum testosterone levels and mortality in men with CKD stages 3-4. Am. J. Kidney Dis.. 2014 Sep 1;64(3):367-74. 16. Yilmaz MI, Sonmez A, Qureshi AR, Saglam M, Stenvinkel P, Yaman H, Eyileten T, Caglar K, Oguz Y, Taslipinar A, Vural A. Endogenous testosterone, endothelial dysfunction, and cardiovascular events in men with nondialysis chronic kidney disease. Clin J Am. Soc. Nephrol. 2011 Jul 1;6(7):1617-25. 17. Carrero JJ, Bárány P, Yilmaz MI, Qureshi AR, Sonmez A, Heimbürger O, Ozgurtas T, Yenicesu M, Lindholm B, Stenvinkel P. Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-stimulating agents in men with chronic kidney disease. Nephr Dial Transpl. 2012 Feb 1;27(2):709-15..

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareMental Foramen and Mandibular Canal in Dry Human Mandibles: A Cross-Sectional Morphometric Analysis English9498Pandey MEnglish Rani AEnglish Bajpai PKEnglishEnglishHuman Mandibles, Mental Foramen, Mandibular Canal, Morphometric Analysis, Nerve blockIntroduction: The mandible is the strongest bone of the skull and movable bone of the viscerocranium other than the ear ossicles. It bears sockets for the lower teeth and provides attachment to muscles of mastication and facial expression.1The Meckel&#39;s cartilage arising from the first pharyngeal arch or the mandibular arch forms framework of the mandible. The gross anatomy of the mandible is composed of two parts: the body and the ramus. The body lies in a horizontal plane, and its superior border consists of sockets for upper teeth. The two vertical bony part is known as rami. The mandible&#39;s body and ramus unite at an angle that varies with age and shows sexual dimorphism in a population. The superior aspect of each ramus has coronoid and condylar processes that articulate with the temporal bone to form the temporomandibular joint.2 The external surface of the body shows mental foramen, and the inner surface of the ramus shows mandibular foramen. The bony canal extending between these two foramina is named a mandibular canal running downward and forward in the body. The inferior alveolar vessels and nerves enter through the Mandibular Foramen, and then it traverses the mandibular canal. Here it gives branches to all lower teeth and finally exits through the mental foramen as mental nerve and vessel.3 The mandibular foramen portrays a cardinal anatomical landmark for oral maxillofacial surgeons in the repositioning of the mandible during sagittal split osteotomies performed to correct structural deformities like prognathism and retrognathia.4 Furthermore, these landmarks are crucial for adequate anaesthesia in dentistry while performing the inferior alveolar nerve block (IANB).5 There is a stoppage of nerve conduction from inferior alveolar nerves and their branches after local anaesthetic agents&#39; infiltration. Anatomical variations of the mandible and insufficient insertion depth into the soft tissue are assumed to be the critical factors for an unsuccessful nerve block.6 The mental foramen is another important landmark in carrying out invasive procedures like a mental or incisive nerve block.7 The racial differences, age and sex variations are well observed concerning foramen&#39;s shape and position.8The foramen&#39;s accurate location and the possibility of a mesial position of an anterior loop of the mental nerve to the mental foramen should be meticulously evaluated before implant surgery to avoid mental nerve injury.9The oedema of the epineurium because of improper placement of the dental implant may involve the mental branch, leading to neurosensory disturbances.10Some studies assumed that the mandibular incisive canal&#39;s large diameter might be a basis of implant failure and neurosensory dysfunction. The collection of soft tissue around the implant impairs the osseointegration and leads to implant failure.11Malpositioning of endosseous implants may compromise the anatomical structures and can affect the sensory supply in the distribution of the mental nerve.12The facial trauma caused by road traffic accidents is usually prevalent among young males aged between 16 and 30 years.13The mandible is the second most common facial fracture site after the nasal bones and represents up to 70% of all facial fractures.14 Mandibular fracture is managed more frequently by the open reduction internal fixation (ORIF) method. In scheduling an ORIF, the detailed anatomy that occupies "danger spaces" in the mandible should be considered carefully. Care should be taken while plating between the tooth root apices and the mandibular canal, which holds the inferior alveolar nerve. Mini­plates and monocortical screws typically are used in this area. In the mental foramen area, isolation and shielding of the mental nerve are essential before placing the plates. A fracture line crossing the inferior alveolar canal can cause a neurosensory disturbance, and the risk is much greater when the displacement exceeds 5 mm.15Oral and maxillofacial surgeons must have extensive knowledge of mandibular anatomy, function, and occlusion—all of which are essential elements of diagnosis, treatment planning, and successful patient outcome. Extensive knowledge about variability in the position of these critical anatomical landmarks in different populations is required to avoid complications related to mandibular anaesthesia. For these reasons, the objectives of the present study were to observe the shape, position and distance from various mandibular anatomical landmarks of the mental foramen. We also measure the length of the mandibular canal. Material and methods: Study type and place: This cross-sectional study was done in the Department of Anatomy in the Medical College of Uttar Pradesh. Inclusion and exclusion criteria: The mandibles not showing any deformity apparently, were included in the study. Mandibles of children and the elderly were excluded from the study. Sample: A total of41 human mandibles were available in the department. we applied the census method to recruit the human mandibles in the study. After applying the inclusion and exclusion criteria, thirty dried adult human mandibles with an intact alveolar margin of unknown gender were used in the present study.[Figure 1]Study duration: The total duration of the study was six months. Methodology: The shape of the mental foramen, its relation to the lower teeth and its location were recorded on both sides of the mandible by using digital Vernier callipers. The shape of mental foramen was categorized as oval or circular.[Figure 2A, 2B and 3]The distance of mental foramen was measured concerning various parts of mandibleL1- Distance of mental foramen from symphysis menti, L2- Distance of mental foramen from the alveolar crest, L3- Distance of mental foramen from the lower border of the body of mandible, L4- Distance of mental foramen from the posterior border of the ramus.[Figure 4] The mandibular canal length was also measured by marking two points perpendicular to mandibular foramen and mental foramen, respectively, and then measuring the distance between these two points. Parameters were measured by using a standard horizontal plane defined by Morront. It says that the mandible when placed on a horizontal surface, the lower border of mandible comes into the highest connection when vertical pressure is used to the second molar teeth.16Statistical analysis: All the data were first entered in Microsoft Excel 2016 and then statistically analyzed using SPSS version 24.0 (SPSS Inc., Chicago, USA). Frequency data were presented as numbers and percentages. The means were compared using Student&#39;s t-test. A p-value less than 0.05 was considered to be statistically significant. Results: The shape of mental foramen was found oval in 80 per cent and circular in 20 per cent of the mandible irrespective of side.[Table 1] In the majority of the mandible, the Mental foramen was found &#39;below the second premolar&#39; both on the right side (73.33 per cent) and the left side (66.67 per cent). The second common position of mental foramen on both right and left sides was between premolars (16.67 and 23.33 per cent, respectively).[Table 2] The mean distance of mental foramen from symphysis menti, posterior border of the ramus, alveolar crest, and lower border of the body of mandible was found 24.38±1.91 mm, 63.62±2.5 mm, 13.15±1.64 mm, and 14.15±1.58 mm on the right side. Whereas on the left side mean distance was 24.01±1.86 mm, 63.49±2.22 mm, 13.23±1.65 mm, and 14.06±1.69 mm, respectively, from the above parameters. [Table 3]The mean length of the mandibular canal on the right and left sides were 52.34±2.67 and 52. ±2.35 respectively. There was no significant difference between the length of the right and left mandibular canal.[Table 4] Discussion: The most common location of mental foramen concerning lower teeth was below the second molar on both sides. Similar results were reported by Parmar 2013 (64.7% rt. and 66.7% lt.), Siddiqui et al. (2011) and Udhaya K.et al. (2013).17,18,19 Discordant to the present study, Gingor et al. (in 2006) reported that the location of mental foramen was between premolars in 71.5% and 22.44% lies below the second molar.20 In the present study on rt. side it was 73.33% rt. and 66.67%, which was discordant to the study done by Parmar et al., Siddiqui et al., and Udhaya K. et al. where it was lying more on the left side.17,18,19 In the present study the most common shape of mental foramen was oval (80%) which is almost similar to study by Siddiquiet al. (2011), Western India on 93 mandible 70% oval and 30% circular mental foramen, Udhaya K.et al. (2013), South India (n=90) 75(83.3%) oval, 15 (16.7%) rounded, Fabian2007, Tanzania (n=100) oval 54(54.0%), rounded 46(46.0%), and Prabodha 2006, Sri Lanka (n=24) 16(66.7%) oval, 8(33.3%) rounded.18,19,21,22The mean distance of mental foramen in mm from Symphysis Menti, Posterior Border of the ramus, Alveolar Crest, and lower border of the body of mandible was 24.21, 63.56, 13.19, and 14.11, respectively. These findings were similar to the study done separately by Udhaya K. et al., Prabodha et al., and Singh et al.19,21,23The mean Length of the Mandibular Canal was 52.17 mm with SD 2.49. Conclusion: The present study reveals that the most common shape of mental foramen is, oval similar to the population of Western Indians, South Indians, Tanzania, and Sri Lanka. Its usual position was below the second premolar. Since it is not possible to palpate the MF clinically, it is necessary to know its accurate place. This will reduce the chances of inadvertent injury during invasive dental procedures like various pre-prosthetic operations and implant insertion. The knowledge of the mandibular canal&#39;s anatomic configuration will also reduce the damage during Osteotomies and placement of endosseous implant surgery. The present study also measured the mandibular canal length that can be correlated with CT related studies of inferior alveolar nerve and vessels. Limitations: As the study was done on a small sample size and mandibles in a college of Uttar Pradesh, the results cannot be generalized for the whole population. So, there is a need for studies with larger sample sizes and different geographical areas for the general application of the results. Acknowledgement: Authors acknowledge the immense help received from the Staff of the Anatomy department and authors whose articles are cited and included in references of this manuscript. Source of Funding: Nil Conflict of Interest: None Declared Authors’ Contribution: All authors have contributed equally in study design, methodology, data analysis, and writing the manuscript. Figure 4: Distance of mental foramen from symphysis menti, alveolar crest,  lower border of the body of the mandible and from the posterior border of ramus such that; L1- Distance of mental foramen from symphysis menti (red), L2- Distance of mental foramen from alveolar crest (green), L3- Distance of mental foramen from the lower border of the body of the mandible (yellow), L4- Distance of mental foramen from the posterior border of the ramus (black) Englishhttp://ijcrr.com/abstract.php?article_id=4144http://ijcrr.com/article_html.php?did=4144 Saladin K, Homan J. Student study guide for use with Anatomy and Physiology. 3rd edBoston: McGraw-Hill;2003, pp.259-60. Breeland G, Aktar A, Patel BC. Anatomy, Head and Neck, Mandible. [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532292/ Standring S, Ellis H, Healy J C, Johnson D, Williams A, Collins P, et al. Grays Anatomy. 39 th ed. Elsevier: Churchill Livingstone, London; 2005. p. 482. Heasman PA. Variation in the position of the inferior dental canal and its significance to restorative dentistry. J Dent 1988;16:36-9 Bremer G. Measurements of special significance in connection with anaesthesia of the inferior alveolar nerve. Oral Surg Oral Med Oral Pathol1952;5:966-88 Thangavelu K, Kannan R, Kumar NS, Rethish E, Sabitha S, Sayeeganesh N. Significance of localization of mandibular foramen in an inferior alveolar nerve block. J Nat Sci Biol Med. 2012;3:156–60. Betz D, Fane K. Mental Nerve Block. [Updated 2020 Aug 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482243/ Green RM. The position of the mental foramen: a comparison between the southern (Hong Kong) Chinese and other ethnic and racial groups. Oral Surgery, Oral Medicine, Oral Pathology. 1987 Mar 1;63(3):287-90 Greenstein G, Tarnow D. The mental foramen and nerve: clinical and anatomical factors related to dental implant placement: a literature review. J Periodontol. 2006 Dec;77(12):1933-43. doi: 10.1902/jop.2006.060197. PMID: 17209776 Parnia F, Moslehifard E, Hafezeqoran A, Mahboub F, Mojaver-Kahnamoui H. Characteristics of anatomical landmarks in the mandibular interforaminal region: a cone-beam computed tomography study. Medicina Oral, Patologia Oral y CirugiaBucal. 2012 May;17(3):e420-5. DOI: 10.4317/medoral.17520. Rosenquist B. Is there an anterior loop of the inferior alveolar nerve? Int J Periodontics Restorative Dent. 1996;16:40–5. Wismeijer D, van Waas MA, Vermeeren JI, Kalk W. Patients&#39; perception of sensory disturbances of the mental nerve before and after implant surgery: a prospective study of 110 patients. Br J Oral Maxillofac Surg. 1997;35:254–9. Haug RH, Prather J, Indresano AT. An epidemiologic survey of facial fractures and concomitant injuries. J Oral Maxillofac Surg. 1990 Sep;48(9):926-32. doi: 10.1016/0278-2391(90)90004-l. PMID: 2395044 Laub DR. Mandibular Fractures. Medscape. 2016 Jan 14. Available online: http://emedicine.medscape.com/ article/1283150-overview#a4 Dreizin, D., Nam, A. J., Tirada, N., Levin, M. D., Stein, D. M., Bodanapally, U. K., et al. Multidetector CT of mandibular fractures, reductions, and complications: A clinically relevant primer for the radiologist. Radiogr. 2016; 36(5), 1539–1564. https://doi.org/10.1148/rg.2016150218 Santini, A., Alayan, I. A comparative anthropometric study of the position of the mental foramen in three populations. Br Dent J. 212, E7 (2012). https://doi.org/10.1038/sj.bdj.2012.143 Parmar A, Shah K, Patel B, Jadav J, Trivedi B, Kothari G. Morphological and Morphometric analysis of mental foramen in dry human mandibles. Int J Med Sci Public Health. 2013;2(3):654. Siddiqui A, Daimi S, Mishra P, Doshi S, Date J et al. Morphological and morphometric analysis of mental foramen utilizing various assessment parameters in dry human mandibles. Int J Stud Res. 2011;1(1):19-22. Udhaya K, Saraladevi KV, Sridhar J. The morphometric analysis of the mental foramen in adult dry human mandibles: A study on the South Indian population. J Clin Diagn Res. 2013;7:1547-51 Gingor K, Ozturk M, Semiz M, Brooks SL. A radiographic study of the location of mental foramen in a selected Turkish population on panoramic radiograph. Coll Antropol. 2006;30(4):801-5 Fabian FM. Position, shape and direction of opening of mental foramen in dry mandibles of Tanzanian adult black males. Ital J AnatEmbryol. 2007;112(3):169-77. Prabodha LBL, Nanayakkara BG. The position, dimensions and morphological variations of mental foramen in mandibles. Galle Med J. 2006;11(1):13-5 Singh SK, Gopinath K, Dhall U, Chhabra S. Variation in the position and number of mental foramen in mandibles of North Indian population. J Anat Soc India. 1992;41(1):47-51.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareAssessment of Renalase Levels in End-Stage Renal Disease Patients on Maintenance Hemodialysis English99104Sudha RangasamyEnglish Vijayasamundeeswari Chinnathambipalayam KandaswamyEnglish Bharanidharan SamiappanEnglishIntroduction: End-stage renal disease (ESRD) is the last stage of chronic kidney disease (CKD) and those patients are at a higher risk of major adverse cardiovascular and cerebrovascular events. Renalase is a novel protein with monoamine oxidase activity and is secreted by the kidney playing a major role in the regulation of blood pressure. Recent studies have suggested serum renalase levels to be related to adverse renal outcomes in patients with chronic kidney disease. Aim: To estimate the levels of serum renalase in ESRD patients on Maintenance Hemodialysis (MHD) and to compare the levels with healthy controls and assess the relationship of serum renalase with other analysed parameters in ESRD patients. Materials and Methods: 60 ESRD patients on MHD and 50 healthy individuals were analysed for serum renalase, fasting blood glucose, urea, creatinine, lipid profile, albumin and haemoglobin levels. Results: The mean level of serum renalase in hemodialysis patients was 68.69±34.52ng/ml which was significantly higher than the controls (45.70±22.18ng/ml)(p-valueEnglish Serum renalase, End-stage renal disease, Maintenance hemodialysis, Chronic kidney diseaseIntroduction: Chronic kidney disease is characterized by loss of kidney function gradually which progresses to End-stage renal disease over the years.  The burden of CKD is enormous that the number of individuals with all stage chronic kidney disease is almost 700 million in 2017, which is more people than those with diabetes, osteoarthritis, chronic obstructive pulmonary disease (COPD), asthma, or depressive disorders. A study on the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) has stated that almost a third of patients with CKD lived in two countries, China (132·3 million cases) and India (115·1 million cases).1 The estimated age-adjusted incidence rate of ESRD is 229 per million population, whereas more than 100,000 new patients enter renal replacement programs annually in India.2 Chronic kidney disease has a major global impact, increasing morbidity and mortality, as well as a financial burden. CKD is a major risk factor for cardiovascular disease (CVD). CKD if is attended to and treated at an earlier stage, the morbidity and mortality can be considerably reduced.  Cardiovascular disease is the most common complication and a chief cause of death in patients with end-stage renal disease (ESRD) accounting for 45% to 50% of causes of death in ESRD patients. CKD is an independent risk factor for CVD and the majority of patients expire due to CVD than progress to ESRD.3In ESRD patients, mortality due to CVD is 10~30 times higher than in the general population. Studies have demonstrated that pathology, manifestations, and complications of CVD differ in the presence of CKD.4 Various reasons have been implicated in the high incidence of CVD in ESRD patients like ventricular hypertrophy as well as non-traditional risk factors, such as chronic volume overload, malnutrition, inflammation, oxidative stress, and other aspects of the uremic milieu. Recently some studies have shown that plasma dopamine and norepinephrine levels are consistently increased in patients with ESRD.5-8 Numerous biomarkers have been tried in recent years which may contribute to the profound increase in circulating catecholamine levels in ESRD patients. Renalase is a recently recognized novel FAD-dependent amine oxidase that is secreted into the blood by the kidney. It degrades catecholamines in vitro and lowers blood pressure in vivo by decreasing cardiac contractility and heart rate and preventing a compensatory increase in peripheral vascular tone.9,10 It is also expressed in the myocardium, skeletal muscles, small intestine, peripheral nerves, adrenal cortex and adipose tissue. Recent data have shown abnormalities in the renalase pathway which are evident in animal models of chronic kidney disease and hypertension. Plasma levels of renalase were said to be markedly reduced in patients with chronic kidney disease and end-stage renal disease.11 Several recent observational studies have associated renalase gene polymorphisms with various diseases like essential hypertension, coronary artery disease, stroke and Type 1 diabetes.12 Since renalase is involved in the catabolism of catecholamines, it was said that it may be used therapeutically in conditions accompanied by increased sympathetic activity. The latest study has suggested that renalase protected against the progression of Diabetic Nephropathy and might be a novel therapeutic target for the treatment of Diabetic Nephropathy.13 However, Ebru Gok Oguz et al have shown that renalase levels are elevated in hemodialysis patients than in the healthy controls.14 Few other studies have stated that the renalase gene can be potentially involved in blood pressure regulation in type 2 diabetes mellitus (T2DM) and the ischemic and arrhythmogenic myocardial changes of T2DM with or without HTN.15 Dziedzic et al have recognized a significantly longer survival time in hemodialyzed patients with high renalase activity compared with patients with low activity of the enzyme.16  The identification of renalase is an important step in developing a more detailed understanding of cardiovascular physiology and might be helpful for physicians in providing timely care for patients with kidney disease. The relationship of renalase with different human diseases have raised it as a substance with potential pathophysiological pertinence and those results might have vast ramifications in diagnosis as well as therapy. Based on this background, a study was conducted to estimate the levels of Renalase in End-stage Renal disease patients on maintenance hemodialysis. Materials and Methods: This study was a cross-sectional observational study conducted over 6 months in a Tertiary care hospital. Institutional ethical clearance was obtained before the study and informed consent was obtained from all the study subjects. The study subjects were stratified into two groups consisting of 60 subjects as Group I, end-stage renal disease patients undergoing MHD and 50 subjects as Group II, apparently healthy controls, who were age and gender-matched. The inclusion criteria were age more than 18 years and patients on regular hemodialysis (3 times weekly) for more than one year. Patients with acute infections were excluded. Group II included healthy individuals over 18 years, not under any medication. For all the subjects, a questionnaire was filled containing the details of age, sex, smoking, alcohol intake, symptoms and aetiology of ESRD, history of medication and duration of hemodialysis. Anthropometric measurements including height, weight, and measurements of systolic and diastolic blood pressure were recorded for all the subjects. Body mass index was calculated and noted. Fasting blood samples were collected for all the study subjects immediately before the HD procedure and transferred to appropriate containers. Samples for renalase were centrifuged and stored at -200C until analysis.  All the samples were analysed for glucose, urea, creatinine, albumin, haemoglobin and lipid profile using a fully automated analyser, Erba EM200. LDL-C was calculated by the Friedwald formula. eGFR was calculated using the MDRD formula. Serum renalase levels were measured by the ELISA method (Wuhan, China). Renalase levels are presented as ng/ml. The sensitivity of the renalase assay was Englishhttp://ijcrr.com/abstract.php?article_id=4145http://ijcrr.com/article_html.php?did=4145 Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 GBD Chronic Kidney Disease Collaboration. Lancet 2020; 395: 709–33.  Singh AK, Farag YM, Mittal BV,  Subramanian KK, Reddy SR, Acharya VN, et al. Epidemiology and risk factors of chronic kidney disease in India – Results from the SEEK (Screening and Early Evaluation of Kidney Disease) study. BMC Nephrol 2013; 14:114.  Subbiah AK, Chhabra YK, Mahajan S. Cardiovascular disease in patients with chronic kidney disease: a neglected subgroup. Heart Asia. 2016;8(2):56-61. Herzog CA, Asinger RW, Berger AK, Charytan DM, Diez J, Hart RGet al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011;80:572–86. Joles, J.A., Koomans, H.A. Causes and consequences of increased sympathetic activity in renal disease. Hypertension. 2004;43:699–706. Zoccali, C, Mallamaci F, Tripepi G, Parlongo S, Cutrupi S, Benedetto FA, et al. CREED investigators. Norepinephrine and concentric hypertrophy in patients with end-stage renal disease. Hypertension. 2002;40(1):41–46. Zoccali, C., Mallamaci F, Parlongo S, Cutrupi S, Benedetto FA, Tripepi G, et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation. 2002;105:1354–1359.  Hausberg, M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, et al. Sympathetic nerve activity in end-stage renal disease. Circulation.2002;106:1974–1979. Xu J, Li G, Wang P, Velazquez H, Yao X, Li Y, Wu Y, et al. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J Clin Invest. 2005 May;115(5):1275-80. Gary V.Desir, Ling Wang, Aldo J.Peixoto.Human renalase: a review of its biology, function, and implications for hypertension. Journal of the American Society of Hypertension.2012;6(6):417-426. Xu J, Desir GV. Renalase, a new renal hormone: its role in health and disease. Curr Opin Nephrol Hypertens. 2007 Jul;16(4):373-8. Gary V. Desir, Aldo J. Peixoto. Renalase in hypertension and kidney disease. Nephrol Dial Transplant.2014; 29: 22–28. Yin J, Liu X, Zhao T, Liang R, Wu R, Zhang F et al. A protective role of renalase in diabetic nephropathy. Clin Sci(Lond).2020; 134(1):75-85. Oguz EG, Gursoy GK, Yayar O, Yildirim T, Cimen T, Bulut C, et al. Increased serum renalase in hemodialysis patients: is it related to left ventricular hypertrophy? Ren Fail. 2016 Sep;38(8):1180-6.  Refaie W, Elewa A. Renalase gene polymorphisms in patients with type 2 diabetes mellitus with and without hypertension. Egypt J Intern Med 2013;25:149-53. Dziedzic M, Powrózek T, Or?owska E, Koch W, Kukula-Koch W, Gawel K, et al. Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients. 2017;PLoS ONE 12(6): e0179218. Baek SH, Cha RH, Kang SW, Park CW, Cha DR, Kim SG, et al. Circulating renalase predicts all-cause mortality and renal outcomes in patients with advanced chronic kidney disease. Korean J Intern Med.2019;34(4):858-866. Malyszko J, Zbroch E, Malyszko JS, Koc-Zorawska E, Mysliwiec M. Renalase, a novel regulator of blood pressure, is predicted by kidney function in renal transplant recipients. Transplant Proc. 2011;43(8):3004–3007. Gok Oguz E, Akoglu H, Ulusal Okyay G, Karaveli Gursoy G, Yildirim T, Merhametsiz O, et al. Increased serum renalase in peritoneal dialysis patients: Is it related to cardiovascular disease risk? Nefrologia. 2017;37(2):189-194. Zbrush E, Koc-Zorawska E, Malyszko J, Malyszko J, Mysliwiec M. Circulating levels of renalase, norepinephrine, and dopamine in dialysis patients. Ren Fail 2013;35:673–679. He B, Hao J, Sheng W, Xiang Y, Zhang J, Zhu H, et al. Correlation between plasma renalase level and coronary artery disease. Pak J Med Sci. 2014;30(5):863-967. Gu R, Lu W, Xie J, Bai J, Xu B. Renalase deficiency in heart failure model of rats- a potential mechanism underlying circulating norepinephrine accumulation. Plos One.2011;6:e14633. Gluba-Brzozka A, Michalska-Kasiczak M, Franczyk-Skora B, Nocun M, Banach M, Rysz J. Markers of increased cardiovascular risk in patients with chronic kidney disease. Lipids Health Dis 2014;13:135. Stojanovic D, Cvetkovic T, Stojanovic M, Stefanovic N, Velickovic-Radovanovic R, Zivkovic N. Renalase Assessment About Kidney Function, Lipid Disturbances, and Endothelial Dysfunction Parameters in Stable Renal Transplant Recipients. Progress in Transplantation. 2017;27(2):125-130. Wang F, Li J, Xing T, Xie Y, Wang N. Serum renalase is related to catecholamine levels and renal function. Clin Exp Nephrol 2015;19:92–98. Przybylowski P, Malyszko J, Kozlowska S, Malyszko J, Koc-Zorawska E, Mysliwiec M. Serum renalase depends on kidney function but not on blood pressure in heart transplant recipients. Transplant Proc 2011;43:3888–3891. Lemiesz M, Tenderenda-Banasiuk E, Sosnowska D, Taranta-Janusz K, Wasilewska A. Serum Renalase Levels in Adolescents with Primary Hypertension. Pediatr Cardiol. 2018 Aug;39(6):1258-1264. Ghaderian SB, Hayati F, Shayanpour S, Beladi Mousavi SS. Diabetes and end-stage renal disease; a review article on new concepts. J Renal Inj Prev. 2015; 4(2): 28-33. Zhang J, Zhang R, Wang Y, Li H, Han Q, Wu Y, et al.  The Level of Serum Albumin Is Associated with Renal Prognosis in Patients with Diabetic Nephropathy. J Diabetes Res.2019: Article ID 7825804, 9 pages. Zbroch E, Musialowska D, Koc-Zorawska E, Malyszko J. Age influence on renalase and catecholamines concentration in hypertensive patients, including maintained dialysis. Clin Interv Aging 2016:11 1545–1550. Dziedzic M, Or?owska E, Petkowicz B, Bednarek-Skublewska A, Solski J, Gozdziewska M. Levels of renalase and advanced oxidation protein products with regard to catecholamines in haemodialysed patients. Ann Agric Environ Med. 2017;24(3):453-458.  

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareStyle of Learning and Thinking and Academic Performance among Secondary School Students: An Explorative Study English105111Vijaykumar RamalingappaEnglish Nithya DamotharanEnglishIntroduction: Learning is a lifelong process and naturally every individual can think and learn based on one’s own pace governed by cognitive, affective and psychomotor domain which has a direct bearing on academic performance. Aim: The study aims to determine the influence of the style of learning and thinking on Academic Performance among ninth class students of different schools. Methods: For this research work, a survey method was adopted and a sample of 300 was chosen through random sampling. Result: The findings show that girls having more of a whole-brain dominance than boys. Urban students have more right brain and left brain dominance than rural students. Aided school students seem to have more Right Brain and Whole Brain dominance whereas Government school students seem to have more Left Brain dominance, which is interesting. There is a significant negative relationship between age and academic performance among high school students, as they grow old, they seem to perform badly in academics. There is no relationship between right-brain dominance and academic performance. The most intriguing finding is a significant (5%) negative relationship between left-brain dominance and academic performance. The student with a dominant left brain seems to perform badly in academics. Conclusion: The creative ability of the brain laid less importance at school levels which hinders new inventions and innovative thinking among school students. This may be attributed to rigid curricula-based teaching-learning methods which need a major renovation including structural and functional changes in the curricular framework. EnglishAcademic Performance, Cognition, Left Hemisphere, Right Hemisphere, Style of Learning, Style of ThinkingINTRODUCTION     The destiny of the nation is being shaped in the classroom - Kothari Commission strongly opined that the progress and prosperity of any county are shaped and moulded employing teaching-learning that takes place in the form of the educational process.1 Education is not a simple process of filling up of the information and knowledge to the empty vessels/bottles, as it is strongly opposed by the contemporary educational psychologists to prove that the whole purpose of education is to modify the behaviour of the learner to the expected lines and aspiration of the society subsequently prepare him to be the responsible individual.  The broader aim and objective of the educational system is to prepare the learner depending upon the social condition and expectations. Hence, the classroom is the place to tune an individual towards progressive thoughts and explorative attitudes. India is a progressive nation facing ample such issues and challenges in the field of education in general and teaching-learning in particular. Style of learning-thinking need to be productive and fruitful which mostly takes place in a vacuum or four walls of the classroom, However, the constructivist (Psychological perspectives) strongly opined that the classroom knowledge dissemination must be practical, intuitive, explorative and every learner has the unique potentiality to construct the knowledge on his own with minimum support by the teacher,  which also equally depends on what drives him to acquire knowledge and the intellectual ability. Neuro-cognitive theories proved that cognition is fully functioning based on the nervous system that controls and operates the brain cells and also based on the dominance of the brain. Hence, Man is the most evolved animal on the earth in terms of brain development, evolutionary cognitive dominance and the well-developed organ system and very well structurally, Co-ordinate organ system, Brain is the basic organ of managing all the organ systems of the human body. The brain as an organ functions like a Central Processing Unit of a computer that controls the body organ system. The brain as an organ has its parts and function in a unique way which also determines the dominance of the left or right brain and its contribution to academic performance has always been an intriguing area and became more interesting for researchers after Sperry&#39;s finding on the split-brain model of intelligence.2 It is after this study there has been some focus on the issue of left or right brain dominance and its effect on academic performance. Ned Hermann who is considered a pioneer in brain dominance study developed from Sperry’s work and came out with the theory wherein a left dominant brain is more analytical and sequential whereas the right dominant brain is more interpersonal and imaginative Literature says right-brain dominance is different from left-brain dominance and it has a role in the context of academic performance.3 A person who is dominated by his or her left brain is said to be better in logical, analytical and linear processing of information whereas the one with right-brain dominance is said to be better in visual, auditory, holistic and nonlinear processing of information.4, Particularly in developing countries like India Educators or the System, do not give any importance or priority to brain dominance while educating or framing the policies. Better learning and expertise can be achieved if the children’s interests, aptitude and brain dominance are taken into consideration before educating or framing educational policies. Teachers at all levels have issues with grabbing or retaining the attention of the children and keeping them focused during a session. On the other hand, children also have issues grasping or understanding what is been taught in the class, mostly due to the way it is taught. This is mainly because of the pattern of brain dominance of each individual.5    The human brain has two hemispheres and they have been naturally/involuntarily functioning the body equally in a crossed manner.6,7 The right side of the body is controlled by the left side of the brain and the left side is controlled by the right side of the brain. There cannot be two masters or two bosses on the same line one part of the brain tries to dominate most of the time or all the time.8 The fact that the left brainchildren are more logical analytical, mathematical and rules-based, they understand through logical analysis, numerical ability and have less trouble in expressing with precise words.9 But right-brainers are creative, imaginative, and relatively good at linguistic abilities and more visual learners who like to see feel and touch. They are more efficient in processing holistic, integrated and emotional information. They often lack focus and move from one thought to another; they use more feelings to understand and are holistic learners. They want to know the whole picture and not parts to understand. They are more into singing, music, arts and have trouble finding the right words to express even though they are clear in thoughts. There are children with whole-brain dominance which is a combination of left and right brain dominance, they use most of the above-discussed techniques separate or in combination to understand and learn.10  REVIEW OF LITERATURE             In the present scenario and society in which we live, particularly in India, left-brain dominance is more preferred and respected than right-brain dominance. The system of education is memory and rote learning and the assessment or grading is done only focusing on the memory faculty of the brain and the system is also designed on the same lines where creativity and imagination are given less importance over memory. Children as they grow are taught and encouraged to work more from the left brain than right by enforcing memory and rote learning whereby the right side that controls emotions and relationships become discordant. Creativity takes a huge beating and is seldom preferred in schools.11 It is better to focus on developing the whole brain and the education system should emphasize it rather than what is happening as of today.  Research studies have found that brain dominance is linked to the selection of occupations in life and academic majors in colleges and universities.12,13 It is based on the analogy between learning styles and rules that govern the majors and the level of attunement between the majors and brain dominance.14,15 Majors like Humanities and Art are the choice of right-brainers, whereas left-brainers prefer Science and Engineering opined that humanities students are right-brainers and natural science students are left-brainers. 16-19  Koju, B et.al. examined the hemisphere brain preference and academic parameters among medial students and reported that 58.3% of students were left-brained, 16% were whole-brained and 23.6% were right-brained.20 Mansour et.al. analyzed the hemispherical brain dominance and academic achievement among nursing students and the findings revealed that 61.6% of students were right-brain dominant and demonstrated that there is a significant relationship between brain dominance and academic achievement.21  The left side of the brain is the place of information processing, memory, logic, analysis, computation, classification and intellect.22 Whereas right is more for controlling, intuition, emotion, attitude, music, songs and physical activities.8 Researchers had come to a conclusion that brain dominance is of two types, left or right dominance but recent studies had suggested that this may not be so. It is more of ‘operate on a continuum’ therefore it is not advisable to classify dominance as left or right and make it look very objective rather it should be more of balanced or whole dominance.23.24 But left-brain dominance is preferred and is more acceptable in schools and classrooms because the system only focuses and stresses on analyzing and memorizing which is the job of the left brain.10 Due to this practice often right-brain dominant students feel suffocated in classes because the creative part which they are good at is never welcomed or entertained.11 Research demonstrated that when students are taught according to their brain dominance they perform better and high scores are achieved when compared to the random teaching methods which do not take into account the brain dominance of the children.25,26,27 When it comes to teaching and learning left-brain dominated students are more interested in deductive teaching and learn faster through that method. Whereas right brain dominated students prefer inductive teaching.28 Right brainers are more into free writing whereas left-brainers are more into research paper writing.29 From the above review, it is evident that there is a need to emphasize the importance of brain dominance and academic performance and how the current system of education is looking at this issue in South India (Tamil Nadu), which is considered as the hub of academics in India. The present study tried to relate brain dominance and academic performance and also understand how brain dominance is looked at in different types of schools, in different areas of residence and is there any difference in brain dominance between genders.  METHODS The purpose of the paper is to analyse the influence of brain dominance on Academic performance among High school students and to assess their profiling effect if any. The participants of the study were high school students of class 8th and 9th from selected Metropolitan schools in Tamil Nadu and the Pondicherry region. All types of schools were included in the study, Government, Aided and Private schools. The sampling technique is multi-staged, a list of Government, Aided and Private schools in Chennai and Pondicherry city were made from which 5 schools at Random were selected under each category, in the first stage. In the second stage, a master list of students whose academic performance information is available and the school is willing to share and the student is also willing to participate in the study without any limitation or pressure was made. From this list, 25 students were selected at random from each school. Therefore 375 Questionnaires were administered and out of which 332 were found to be complete and fully usable therefore the final sample size was fixed at 332. The tool used for data collection was a structured questionnaire which consists of profiling questions in the first part and the part brain dominance measure was quantified through a five-point Likert’s scale SOLAT (Styles of Learning and Thinking) developed by Venkataraman was the second 30  Academic performance is the mean score of the students in their subjects on the continuous assessment system, which is a test for every month in an academic year. This research study was conducted as partial fulfilment of coursework of the Master of Education (M.Ed.) dissertation report. Pondicherry University reserves the rights of the publication. FINDINGS Brain dominance was largely classified into three categories which are as follows; Right brain dominance, Left brain dominance and Whole-brain dominance. A student whose relative score is considered as high on the right brain assessment or performance is treated as right-brain dominance and any student whose relative score is considered as a high score on the left brain is termed as left-brain dominance and a balanced score is termed as whole-brain dominance. From Table-1, it can seem from the first 5 rows that there is no effect or gender difference in the Right or Left-brain dominance as the significance values for the F tests are above 0.05. But there is a significant difference (F significance is less than 0.05) between boys and girls in whole-brain dominance with Girls having more of a whole-brain dominance than boys. Among residence differences (second set of 5 rows) there is a significant (5%) influence on Right and Left-brain dominance but not on the Whole-brain. As the common understanding Urban students have more Right and Left brain dominance than rural students. Among the type of schools (third set of 5 rows), there is a significant (5%) difference in Right, Left and Whole-brain dominance between the types of schools they are studying. Aided school students seem to have more Right Brain and Whole Brain dominance whereas Government school students seem to have more of Left-Brain dominance, which is interesting. From all this, it can be concluded that Type of school has a major influence on Right and Left and Whole-brain dominance. Type of Residence influences Right and Left-brain dominance and Gender only influences Whole-brain dominance.  The profile variable differences on academic performance are provided in Table-2. There is a significant difference between boys and girls in the Academic performance totally and individually as the F significance for all are below 0.05.  Girls seem to outperform boys in all the components of academic performance, with a better mean score.  Area of Residence does not seem to influence much on academic performance except English where urban students are better than rural students, which has a significant (5%) F statistics. Type of school like gender has a major effect on Academic performance individually and totally. Private school students seem to perform much better than aided and government school students in all aspects of academic performance with all the F significance below 0.05 and considerable higher mean scores. It can be concluded that Gender and Type of school have a major influence on Academic performance. The relationship between brain dominance and Academic performance is provided in Table-3. It can be seen that there is a significant negative relations ship between age and academic performance among high school students, as they grow old, they seem to perform badly in academics. Moving to the important findings of the study there is no relationship between right-brain dominance and academic performance, totally or individually. The most intriguing finding is there is a significant (5%) negative relationship between left-brain dominance and academic performance. A student with a dominant left brain seems to perform badly in academics. This could be due to brain functioning where the Left brain is more for creative aspects and less for memory and the Indian system of education is purely memory-based and focuses only on the memory faculty of the brain. Therefore, a left dominant student is likely to perform badly in academics. It is the whole brain dominance that is ideal for students, whole-brain dominant students perform much better in academics and there is a significant (5%) positive relationship between whole-brain dominance and academic performance, individually and totally. This could be cliché but a balanced brain or whole-brain dominance is ideal for a kid as the creative and memory faculty need to function well for a good performance in academics and life.  CONCLUSION Neuroscientists believed that two sides of the brain collaborate to perform a broad variety of tasks and two hemispheres communicate through corpus callosum no matter how lateralized the brain can get, though, the two sides still work together.31 Theory of Brain Dominance says that there is always an inclination on the part of the individuals in using one hemisphere over the other. The analytical and rational qualities are with the left hemisphere while the right is more about intuition and visualization. This research work may help in identifying the dominant side of the brain and how one can use it effectively to optimize the learning experience. Brain dominance is a pattern where different hemispheres of the brain are used for learning and listening activates and most often one side of the brain is consistently used over the other. ’Brain dominance was expressed in terms of how we prefer to learn, understand and express something’.32 The term brain is often associated with thinking. However, many functions are associated with a particular hemisphere of the brain like Motor control and Language ability. But to conclude that one hemisphere is dominant over the other is not fair for most activates and many individuals possess the quality of double dominance where both the hemispheres are used equally, this is made possible by their preferential mode of thinking.33 Individuals who possess or display double dominance will be able to use both hemispheres equally for logistical thought processing and intrinsic creativity. This quality is termed whole-brain dominance or integrated dominance. Koju, B et.al. analyzed the hemisphere brain preference and academic parameters and found that 58.3% of students were left-brained, 16% were whole-brained and 23.6% were right brained.20  Students do learn better when the learning preference characteristics are being attended properly by their teachers, hence, it is imperative the educators must be aware of student’s strengths including multiple intelligences, learning preferences, emotions, logical ability, language proficiency, numerical ability, imagination etc., Mansour et.al. study revealed that the hemispherical brain dominance and academic achievement and found that 61.6% students were right-brain dominant and established that there is a significant relationship between brain dominance and academic achievement.21 The study aimed to comprehend the pattern of brain dominance and how they relate to academic performance in the Indian context and system of education. The results are interesting as right-brain dominance is bad and left-brain dominance is good for academics but the ideal one is whole-brain dominance. This finding does not give a good signal as the more important ability of the brain, the creative ability is given less importance and its dominance is not encouraged. In the given scenario, how can the young and future generations be creative and innovative? The Indian education system is in the process of making robots or machines that are expected to execute and not be creative or innovative. This is one of the reasons for Brain Drain especially talent of higher-order and many moving to the western world for higher education and preferring to stay back there thereby creating a vacuum for innovation and creativity in India. It is time the Government and the policymakers understand this and take a relook at the system of education including curriculum, instructional strategy, so that desirable educational goals among the students may be set thereby national goals shall be attained through educational means. Acknowledgement:- I would like to record my deep sense of acknowledgement to Dr.M.Leeladharan, Assistant Professor, Department of Library & Information Science, Pondicherry University for his consistent effort in completing this paper and Dr.S, Thiyagarajan, Assistant Professor, International Business, Pondicherry University for his tireless effort to finalise in the quantitative analysis. Conflict of interest and source of funding:  NIL. There is no conflict of interest among the two authors and we have not received any funding for carrying out this study.  The present study is conducted as partial fulfilment of the course work of the Master of Education (M.Ed.) dissertation report.  All work of the research study was carried out by the first author including conceptualization, analysis and interpretation and the data collection responsibility essentially carried out by the second author. Englishhttp://ijcrr.com/abstract.php?article_id=4146http://ijcrr.com/article_html.php?did=4146 Kothari DS, Chairman AR. Report of the education commission 1964-66. New Delhi, National Council of Educational Research and Training; 1967. Sperry RW. Forebrain commissurotomy and conscious awareness. J. Med. Philos 1977 Apr;2(2):101-26. Morris RJ. Left brain, right brain, whole brain? An examination into the theory of brain lateralization, learning styles and the implications for education; 2006. Soyoof A, Jokar M, Razavizadegan MA, Morovat E. The effects of learners’ brain hemisphericity on their degree of vocabulary retention: A case study of Iranian high school students. Procedia Soc Behav Sci 2014 May 6;98:1844-9. Morris M. The SPD Companion. Right Brain vs. Left Brain Learning Styles 2006;10. Hergenhahn B, Olson MH. An Introduction to theories of learning 7th Edition. Kök ?. The relationship between students’ reading comprehension achievement and their attitudes towards learning English and their abilities to use reading strategies about hemispheric dominance. Procedia Soc Behav Sci 2010 Jan 1;3:144-51. Tendero J. Hemispheric dominance and language proficiency levels in the four macro skills of Western Mindanao State university college students. Brown HD. Principles of language learning and teaching. Oflaz M. The effect of right and left brain dominance in language learning. Procedia Soc Behav Sci 2011 Jan 1;15:1507-13. Revell J. Left, right and VAK. Pract Engl Teach 1992 Jun;9. Kolb DA, Rubin IM, McIntyre JM, editors. Organizational psychology: A book of readings. Prentice-Hall; 1979. McCarthy B. The 4mat system research: Reviews of the literature on the differences and hemispheric specialization and their influence on learning. Barrington, IL: Excel. Gordon VN, Coscarelli WC, Sears SJ. Comparative assessments of individual differences in learning and career decision making. J Coll St Personnel 1986 May. Rowe FA, Waters ML, Thompson MP, Hanson K. Can personality-type instruments profile majors in management programs?. J. Educ. Bus 1992 Oct 1;68(1):10-4. Coulson LT, Strickland AG. The minds at the top: An analysis of the thinking style preferences of superintendents of schools and chief executive officers. J Creat Behav. 1983. Herrmann N. The Creative Brain. NASSP Bull 1982 Sep;66(455):31-46. Katz AN. Creativity and individual differences in asymmetric cerebral hemispheric functioning. Empir. Stud. Arts 1983 Jan;1(1):3-16. Lavach JF. Cerebral hemispherectomy, college major and occupational choices. J Creat Behav 1991. Koju B, Joshi LR, Chaudhary S, Shrestha A. Hemispheric Brain Preference and Academic Parameters in Medical Students: A Cross-sectional Study. J. Lumbini Med. Coll 2019;7(2):37-43. Mansour EA, El-Araby M, Pandaan IN, Gemeay EM. Hemispherical Brain Dominance and Academic Achievement among Nursing Students. J Nurs Health Sci 2017;6(3):32-6. Munzert AW. The constitution of the Philippines. Saleh A, Iran-Nejad A. Wholetheme Constructivism and Whole-Brain Education: Educational Implications of the Research on Left and Right Brain Hemispheres. Saleh A. Brain hemispheric and academic majors: A correlation study. Coll. Stud. J 2001 Jun 1;35(2):193. Brennan PK. An analysis of the relationships among hemispheric preference and analytic/global cognitive style, two elements of learning style, method of instruction, gender, and mathematics achievement of tenth-grade geometry students (Doctoral dissertation, St. John&#39;s University). Dunn R, Sklar RI, Beaudry J, Bruno J. Effects of matching and mismatching minority developmental college students’ hemispheric preferences on mathematics scores. J Educ Res 1990 May 1;83(5):283-8. Jarsonbeck S. The effects of a right-brain mathematics curriculum on low-achieving fourth-grade students. Krashen S, Seliger H, Hartnett D. Two studies in adult second language learning. Kritikon Litterarum 1974;2(3):220-8. Breien-Pierson R. The influence of brain hemispheric on the composing process of twelfth graders. Venkataraman D. Styles of learning and thinking–administrator’s manual. New Delhi: Psycom Services; 1994. Liederman J. The dynamics of interhemispheric collaboration and hemispheric control. Brain Cogn 1998 Mar 1;36(2):193-208. Herrmann N. The Creative Brain. Kingsport Tennessee: Quebecor Printing Group; 1995. Gabbard SH. Examining the stabilising characteristics of footedness. Laterality 1997 Mar 1;2(1):17-26.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareAwareness Regarding Pubertal Changes Among Adolescent Boys: A Review English112116Bibin KurianEnglish Archana MauryaEnglishEnglishPuberty, Rebellious behaviour, Sexuality and stressINTRODUCTION The term adolescence comes from the Latin Word “Adolescere” meaning to grow to maturity. "Adolescence" is the age between 10 and 19 years. Between the age of 10 and 19, the boys have many aspects to follow. On average, girls attain puberty at the age of 10 and boys by 12. Adolescents contribute one-fifth of the world’s population. In India, out of 100, adolescents contribute 23%, which means around 230 million children are in the age group of 10 to 19 years.1 The meaning of adolescence is ‘to become apparent or prominent’ or ‘achieve identity.’ Adolescence is defined as a phase of life characterized by rapid physical growth and development, physical, social and psychological changes and maturity, sexual maturity, experimentation, development of adult mental processes and a move from the earlier childhood socio-economic dependence towards relative independence. In other words, we can say it is a transformation from child life to adult life where the child lives in a family and the adult lives in the society. They have their own and different needs that cannot be avoided by their parents. The changes or development that takes place in adolescents are not the same for all of the sequences may be different. Most probably, physical maturity can be achieved earlier than psychological or social maturity.2 Sexuality education and curriculum  In India, for private schools, it is not compulsory to include sexuality education in the curriculum. Even nobody knows how many private schools are following a comprehensive syllabus. It is compulsory for the private schools that are following the Central Board of Secondary Education (CBSE) syllabus to add a portion of sex education in their syllabus but they are very few. Many of the private and public schools that are affiliated with State boards of secondary education have not included a single portion of sexuality education in their curriculum.3 Census In the year 2011, there was a Census. According to that adolescents contribute one-fifth of the population of the State.  In Maharashtra itself, adolescents contribute 19 percent of the total population.4 Population Council in India says that India has 315 million children in the age group of 10-24 and they represent 30% of the country’s population. 50,848 youths were included in the study. It is found that neither fathers nor mothers were ready to talk on the topics like romantic relationships and reproductive processes with the boys. These kinds of issues were discussed only by the mothers with their daughters.5 The attitudes and expectations of the current younger generation change day by day. There was a poll conducted by India Today magazine along with AC Nielsen-ORG-MARG which shows that one among the four women living in big cities of India between the age group of 18 and 30 had indulged in sex before marriage. It is revealed that the age of indulging in sex is also declined. 42% of the samples were indulged in sexual activity between the age of 19 to 21. The most interesting thing is, 25% of the adolescents in the age group of 15-18 were very keen to have sexual activity.6 In the year 2006-2007, a youth survey was conducted by the International Institute of Population Sciences (IIPS) and the Population Council in Maharashtra. The samples were unmarried men and women who were in the age group of 15-24 years and married women and men in the age group of 15-29 years. They found that most of the women in both groups do not have any sexual knowledge. There also 18% of men and 3% of women have had indulged in sex before marriage. Compared to women, men have more access to information, but it was not the right source. The fact is, in this era also, women do not feel free to talk about sexuality. The results also show the fact that 33% of unmarried women were aware of the fact that they could get pregnant from their first sexual encounter as compared to 46% of men.7 Reality Today’s young generation are at high risk of conditions that affect their health because of their personal choices, how the environment influence and changes in their lifestyle including diseases. The other conditions include disorders from substance use, injuries results from road traffic accidents, attempted and successful suicides, infections that are transmitted sexually, teenage pregnancies and unplanned pregnancies, homelessness, violence and several others.8 Even though we live in a fast-forwarding and fast-growing country, today also there are restrictions or hesitations for the elders in our society to have a casual or free discussion of the reproductive health issues with teenagers or even with their sons.9 Elders in society believe that if they talk about sexuality with adolescents, they may get into sexual crimes. Because of this kind of thinking of the elders, teenagers or adolescents get very little or no knowledge about sexuality either from their parents or from school.10 As a result of the hesitation of the parents to discuss sexual health and sexuality and the lack of incorporation of topics related to sexual health, adolescents never get any help from their parents as well as the education system in this regard. The most interesting thing is, many of the health centres are also of no use for this matter.11 When adolescents do not get enough knowledge from their parents, school and health centres, with no choice left, they turn towards their friends, local books and media. We can say that not only in India, almost in all countries, this is the situation and the teenagers or adolescents pass through this crucial phase of their life without the help from where they are supposed to. So, they are at high risk of getting road traffic injuries, sexually transmitted infections and if the situation is not handled properly at the time, this can lead to much bigger health problems for them in their later life.12 There are certain changes in the body of an adolescent or teenage boy which are unexpected and upsetting experiences for many. One of the most suitable examples for this is ejaculation. It is believed to be the most upsetting experience for an adolescent who does not have much knowledge regarding the changes that happens at the time of puberty or the adolescent period. Shipman conducted a research study on the psychodynamics of sex education. It is revealed that only 15% of the samples had some knowledge about ejaculation and understood the concept of ejaculation before its occurrence. Thus, lack of preparation can lead to negative experiences in their lives and sometimes it can be fatal also.13 Sometimes the information passed to the adolescents or the information they got from the other sources may not be adequate or accurate with their own experiences and that will affect their emotional balance.14 It is just as such factors influence adolescent girls&#39; perceptions of the menarcheal experience.15 Most of the time; adolescents hesitate to ask questions or doubts regarding their reproductive or sexual health problems to elders keeping in mind that what elders will think of them. Ultimately, this leads to self-treatment of their problems or approach persons who are not legally permitted to practice medicine.16 There was a bulletin that provides information about how the parents and caretakers have to interact with the adolescents to enhance their positive development.  Adolescents discover themselves when their intellectual growth transfers from concrete form to abstract thinking. They try to define what they are and their relationship with the world. At that time, they ask themselves these four questions: Who am I? (Related to their sexuality and social roles) Am I normal? (Do I fit in with a certain crowd?) Am I competent? (Am I good at something that is valued by peers and parents?) Am I lovable and loving? (Can someone besides Mom and Dad love me?) At many times parents and relatives of the adolescents work together. They should understand that the answers to these questions are very important to them. Also, they have to give them a chance to explore them and to find themselves the answers to these questions.17 Research findings A research study was conducted at Nand Nagari, Delhi. The setting of the study was slums and the samples were adolescent boys and girls. The findings of the study show that the adolescents were unaware of sexuality or sexuality-related matters. Half of the study populations knew the fact that secondary sexual characters for boys are growing of moustache and beard. Only 16.8 percent of the samples were aware of ejaculation at night and 12.9 percent were aware of pubic hair (Graph 1).  The study also included knowledge about the changes that happen in the body during puberty. Girls had more knowledge regarding pubertal changes than boys. Only 58 per cent of adolescents knew the fact that moustache and beard are the signals that indicate the initiation of puberty. There is 12 per cent of adolescents who knew that ejaculation at night and genital growth are also a part of pubertal changes. The remaining 88 per cent were not even aware that these changes had already happened in their body. Some adolescents don’t even know what pubic hair is. All these indicate that there is a need for mass education about puberty and the changes that happen in the body at the time of puberty for adolescents especially for boys.18 Awareness regarding puberty changes in secondary school children was the name of the cross-sectional study which was conducted at Bagalkot, Karnataka. There were three objectives; to evaluate the awareness regarding puberty changes in both boys and girls, to find out the necessity of the subject of sex education in the curriculum and the final one was to find out the source of information of the respondents. The students from the 8th, 9th and 10th standards were selected for the study. There were a total of 502 students selected for the study. Out of that, 394 (78.49%) were boys and 108 (21.51%) were girls. Regarding secondary sex characters, 19.80% of the boys and 9.25% of the girls had correct knowledge.  When 55.56% of the girls discussed sex matters with their parents but instead of discussing sex matters with parents, 45.18% of boys discussed it with their friends. 41.23% of the students were in favour of including sex education from higher secondary school. Regarding the source of information, 51.52% of the boys received it through television, whereas 40.74% of girls got the information through television.19 A study was conducted in the Glasgow area to assess the changes in body composition in adolescent boys. A total of 47 healthy students were selected and the body composition was studied at 10 and 13 years. 22 of the students had reached a total puberty rating (TPR) greater than 4 and the remaining students were below 4 when it was checked at the age of 13. It is also observed that between the age of 10 and 13, there are very fast and dynamic changes in the body composition happens.20 A study that was focused on the knowledge of adolescent boys about the pubertal changes was conducted in Udupi District. The study was conducted in selected schools. It is found that in the pre-test, 73% of the boys had average knowledge and only 22% of boys had good knowledge. Then teaching was given to the children and good knowledge was increased to 86 %.21 (Table 1). CONCLUSION                 The important life event that happens in the adolescent period is the changes that happen in the body at the time of puberty. That includes physical, emotional and psychological changes. These changes are very important for their future development.  Educating about the growth and development in the body is very important for adolescents that will help to reduce the tension and anxiety at certain times of development if they do not possess adequate knowledge regarding these changes. Also, it will enable them to take the right decision about sexuality for the current situation and even for their future life. But unfortunately, neither the parents nor the education system in India doesn’t take any interest or initiative in educating adolescents. As a result, they seek the answer for their own and some get more or less correct answers and most are in middle. So unable to get cope up with the situation, they approach measures like drinking, smoking and drugs. Adolescents need guidance to channel the drive toward risk-taking behaviour into less dangerous and more constructive pursuits. So there is a need to educate the adolescents about the normal physiological changes occurring during the adolescence phase to help them to cope up with the various changes occurring and help to identify themselves as an individual. Acknowledgement The authors are very much thankful for the support provided by the researchers whose articles and findings are cited and included in references of this manuscript. The authors are also grateful to authors/editors / publishers of all those ar­ticles, journals and books from where the literature for this article has been reviewed and discussed. Ethical clearance- Taken from Institutional Ethics Committee, Regd. No. ECR/440/Inst/MH/2013/RR-2016, Datta Meghe Institute of Medical Sciences (Deemed to be University). Source of funding- Self.      Conflict of Interest – Nil. Answer the following questions. Data collected from three regions only, whether it is sufficient to reach any conclusion?: Very few studies had conducted on the topic of pubertal changes among adolescent boys. There are many studies related to pubertal changes but most of the samples are girls. There are one or two studies that included both boys and girls. In my study, I have included only boys. That’s why only “boys” are mentioned in the title.  As mentioned in summary no discussion about any physical symptoms like nausea, headache were found or not is mentioned in observations: That review I have got from the literature review of a study. I have searched a lot to find out the details of that review but it says that the article related to that topic is removed from the internet. Data statistics should be given: Recently I have added statistical data in the corrected one. Arrange the references according to the journal’s instructions: Ok Englishhttp://ijcrr.com/abstract.php?article_id=4147http://ijcrr.com/article_html.php?did=4147 Stroufe, L.A., & Cooper, R.G., “Child Development: Its Nature and Course”, New York: Alfred A. Knopf 1988.  Hamburg, D.A., “Toward a strategy for healthy adolescent development” American Journal of Psychiatry, 1997, 154, 7-12. Report to the United Nations Human Rights Council for the Universal Periodic Review of the Republic Of India on the Lack of Comprehensive Sexuality Education in India. https://lib.ohchr.org/HRBodies/UPR/Documents/Session1/IN/YCSRR_IND_UPR_S1_2008_YouthCoalitionforSexualandReproductiveRights_uprsubmission.pdf Economic Survey of Maharashtra, Directorate of Economics and Statistics, 54th issue for the year 2014-15, http://admin.indiaenvironmentportal.org.in/files/file/Economic%20Survey%20of%20Maharashtra%202014-15.pdf. https://www.popcouncil.org/uploads/pdfs/2010PGY_YouthInIndiaExecSumm.pdf https://www.indiatoday.in/magazine/cover-story/story/20050926-india-today-sex-survey-single-young-women-across-urban-india-shaking-off-conservatism-786962-2005-09-26. Project Youth in India: Situation and Needs Study, https://www.popcouncil.org/uploads/pdfs/2010PGY_YouthInIndiaExecSumm.pdf World Youth Report 2003: The Global Situation of Young 14. People. New York: Department of Economic and Social Affairs, United Nations; 2004. P.429. Available from: http://www.un.org/esa/socdev/unyin/documents/worldyouthreport.pdf, accessed on January 9, 2013. Fox LS. Adolescent male reproductive responsibility. Soc Work Educ. 1983 fall; 6(1):32-43. PubMed PMID: 12339621. Hoang, D.H. What do pupils and students know about contraceptive methods? SUC KHOE SINH SAN. 2001; 2:23, 25. Khan MA, Rahman M, Khanam PA, Barkat-e-Khuda, Kane TT, Ashraf A. Awareness of sexually transmitted disease among women and service providers in rural Bangladesh. Int J STD AIDS. 1997 Nov; 8(11):688-96. Pub Med PMID: 9363543. Mustafa MA, Mumford SD. Male attitudes towards family planning in Khartoum, Sudan. J Biosoc Sci. 1984 Oct; 16(4):437-49. Pub Med PMID: 6490682. Shipman, G. The psychodynamics of sex education. In Muuss, R. E. (ed.), Adolescent Behavior and Society: A Book of Readings. Random House, New York, 1971. p. 326-39. Ruble DN, Brooks-Gunn J. The experience of menarche. Child Dev. 1982 Dec; 53(6):1557-66. PubMed PMID: 7172781. Whisnant L, Zegans L. A study of attitudes toward menarche in white middle-class American adolescent girls. Am J Psychiatry. 1975 Aug; 132 (8):809-14. PubMed PMID: 1147064) Piaget J, Inhelder B. The Psychology of the Child. New York, NY: Basic Books Inc; 1969. P.1557-9. Perkins, D.F., “Adolescence: The Four Questions”, University of Florida Extension, 2001. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.514.7533&rep=rep1&type=pdf Dalvir Singh, Health and Population - Perspectives and Issues 23 (4): 198-204, 2000. Dorle AS, Hiremath LD, Mannapur BS, Ghattargi CH. Awareness regarding puberty changes in secondary school children of Bagalkot Karnataka- A cross-sectional study. J of Clin and Dig Re Study. 2010Oct: 4:3016-3019. Riumallo J, Durnin JV., “Changes in body composition in adolescent boys”, Eur J Clin Nutr. 1988 Feb; 42(2):107-12. Ajith Kumar Shetty, Alphoni PG, Beena KJ, Tandra Kabiraj, Benita Paul, Anil Raj A. & Soumya Alex, Effectiveness of planned teaching programme on knowledge regarding pubertal changes among adolescent boys in selected high school of Udupi District, NUJHS Vol. 6, No.2, June 2016, ISSN 2249-7110.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareVitamin D Status in Covid-19 Patients Admitted to ICU in a Tertiary Care Hospital English117124Ramashetty REnglish Manjunathaswamy AHEnglish Viswanath NEnglish Chandrashekarappa SMEnglish Kalvapudi DEnglishBackground: The pandemic outbreak of COVID 19 has affected people worldwide. Studies have shown that deficiency of vitamin D is associated with increased susceptibility to respiratory infection. Aim: To evaluate vitamin D status and the possible association of vitamin D levels and biomarkers in COVID-19 patients admitted to the intensive care unit. Methodology: A cross-sectional study done confirmed COVID 19 patients were admitted to ICU. Blood count, vitamin D, inflammatory markers and blood gas parameters were measured. Duration of stay and outcome were recorded. Statistical analysis was done using SPSS V.25 Results: Study done on 155 patients with COVID 19 showed 94.2% participants had Vitamin D deficiency (Vitamin D 20 ng/mL and vitamin D 50 years and the females had lower vitamin D levels. The majority of COVID-19 patients in whom mortality was the outcome, had lower levels of Vitamin D. EnglishVitamin D, COVID 19 infection, Inflammatory markers, SARS CoV-2Introduction:            A novel human coronavirus, first detected in a cluster of unexplained pneumonia cases in Wuhan, China has caused a global outbreak and has become a major public health problem worldwide. 1 The World Health Organization officially named this new coronavirus disease as COVID-19 and the virus causing it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2 SARS CoV-2 affected patients present from mild symptoms of upper respiratory tract infection to severe respiratory failure. Clinical data obtained from COVID-19 patients have reported high concentrations of cytokines admitted to the ICU, which indicates the presence of cytokine storm in severe COVID-19 patients. Many COVID-19 patients have died due to complications such as ARDS, pneumonia, acute kidney failure, acute heart failure etc, which is likely attributable to uncontrolled acute inflammation and cytokine storm. 3,4             Vitamin D is a fat-soluble steroid derivative and a prohormone, which plays an important role in bone health by maintaining calcium and phosphate homeostasis. However, research in the last two decades has discovered novel actions of vitamin D on the cardiovascular system, nervous system, respiratory system and immune response. 5,6 Recent experimental pieces of evidence have shown that deficiency of vitamin D is associated with increased susceptibility to infection and autoimmune disorders. 7 Evidence from observational studies shows an association between vitamin D deficiency, chronic airway diseases and respiratory infections indicating the possible role of vitamin D in reducing the risk of respiratory tract infections. 8 In a review and meta-analysis of 25 randomised controlled studies, Martineau et al. have mentioned that vitamin D helps in protection against acute respiratory tract infection. 9 In vitro and in vivo studies have also shown that vitamin D plays an active role in the modulation of innate and adaptive immune responses. 10           Observational studies have shown that COVID-19 positive patients have a higher incidence of low vitamin D levels than COVID-19 negative patients. It is also seen that there is a high prevalence of vitamin D deficiency and insufficiency in a cohort of patients with moderate-to-severe acute respiratory syndrome due to COVID-19. Growing circumstantial evidence and recent studies have linked the severity and mortality of COVID-19 to the vitamin D status of the patients. A cross-sectional analysis across Europe showed that COVID-19 mortality was significantly associated with vitamin D status in different populations. 11 Another Indonesian retrospective cohort study of 780 Covid-19 patients indicated that the majority of death cases had low vitamin D levels and that vitamin D status was strongly associated with Covid-19 mortality. 12 Recently, some articles also have suggested the possible involvement of vitamin D in reducing the risk of respiratory tract infections, especially from influenza, rhinovirus and previous coronaviruses by enhancing immune response. 13        Observational studies have frequently reported that higher levels of vitamin D were associated with low levels of inflammatory markers including CRP, IL-6 and TNFα in healthy populations and in those with proinflammatory conditions, such as diabetes, arteriosclerosis and inflammatory conditions. 14 Low levels of vitamin D have been associated with increased risk of viral respiratory tract infections and an increase in inflammatory cytokines. Thus, this study aimed to evaluate the possible association of vitamin D levels and various biomarkers in moderate to severe COVID-19 patients admitted to the intensive care unit. Methodology:            This is a cross-sectional study. Ethical clearance was obtained from the institutional ethical committee, JSS Medical College, Mysuru (LetterNo. JSSMC/IEC/1909/01NCT/2020-21). 155 RT-PCR confirmed COVID-19 patients aged 18 – 60 yrs, admitted to ICU of JSS Hospital, Mysuru, Karnataka, India and willing to participate in the study were recruited. Informed consent was obtained from the study participants. No specific exclusion criteria were considered, except patients not willing to give consent for the study. Information regarding socio-demographic variables, medical history and comorbidities of the patients were collected using a pre-tested and validated questionnaire. Vital signs like Pulse rate, Blood pressure, Respiratory rate and SPO2 were recorded from the patients. SOFA score at admission was calculated.           Laboratory findings like blood count, HbA1C, Vitamin D, Procalcitonin, C-reactive protein, Ferritin, D-dimer, LDH, Renal function tests, liver function tests and blood gas analysis parameters were obtained from the case records. Respiratory parameters such as the fraction of inspired oxygen (FiO2) was obtained and PaO2/FiO2 ratio was calculated. Statistical Analysis:        Data were entered in Microsoft Excel and analyzed using SPSS V. 25 (Licensed to the institution). Descriptive statistics were used to calculate Mean, Median, Standard Deviation, Inter Quartile Range, Proportion etc., and continuous variables were expressed as mean ± standard deviation (SD) or median and interquartile range. Based on the distribution, parametric (independent t-test and ANOVA) tests or non-parametric (Mann-Whitney U Test, Kruskal Wallis) tests were used to compare the variables for differences in the Vitamin D levels and Chi-square analysis was used to find the association of categorical variables with Vitamin D levels. Results:        The study included a total of 155 (111 male and 46 female) COVID-19 patients admitted to ICU. The mean age group of the study participants was 55.7±11.8 with a minimum age of 16 yrs. and a maximum of 69 yrs. 71.6% were males and 28.4% were females. 78% of the individuals had one or the other co-morbidities. 54.1% were diabetics, 54% were hypertensives, 13% had a history of ischemic heart disease and 23% had other co-morbidities like asthma, chronic kidney disease, chronic obstructive pulmonary disease, epilepsy, anaemia, pancreatitis, hypothyroidism and hepatitis B. The median SOFA score at admission was 3 (2-4). 43% of the patients expired and the remaining 57% were discharged (Fig 1). 90.32% of patients had ARDS as assessed by PaO2/FiO2 ratio lower than 300 mmHg (Fig 2) and a major proportion of patients with severe ARDS had Vitamin D levels of < 20 ng/ml. The median number of days of stay in the hospital was found to be 11 (7-17), with a minimum of 2 days and a maximum of 41 days. Other clinical characteristics of patients admitted to the Intensive Care Unit has been represented in Table 1.           Concerning Vitamin D, while we initially started the study to compare the profile of covid-19 patients getting admitted to ICU with normal and lower levels of Vitamin D, at the end of the study, when the data was analysed, it was seen that majority i.e 94.2% of the study participants had Vitamin D deficiency and only 5.8% had normal Vitamin D >30 ng/ml. Out of those who had lower serum levels of Vitamin D, 68.4% had Vitamin D levels 50 yrs was 17.19±9.95.          We divided patients into two groups by serum vitamin D level in patients: vitamin D > 20 ng/mL and vitamin D 30 ng/ml. Out of those who had lower serum levels of Vitamin D, 68.4% had Vitamin D levels < 20ng/ml.  Study participants > 50 years and the females had lower vitamin D levels and there was significant statistical association only between sex and Vitamin D levels. Similar to our study, J L Hernandez et al, also have shown that hospitalized COVID-19 patients had lower 25OHD levels and a higher prevalence of vitamin D deficiency when compared to the population-controlled group. But, in their study Serum 25OHD values were lower in men than in women. 15 A Study by A Jain et al. on the Indian population also compared Vitamin D levels between asymptomatic COVID-19 patients and severely ill patients requiring ICU admission and reported that Vitamin D levels were markedly low in severe COVID-19 patients. 16 Serum 25(OH)D concentrations tend to decrease with age and thus low serum 25OHD levels are frequently found in elderly individuals which may be important for COVID-19 because more severity and case-fatality rates are seen in elderly people. 17 Also, low 25OHD levels are seen in those individuals with comorbidities, such as hypertension, diabetes, or cardiovascular diseases, which have also been reported as poor prognostic factors for COVID-19. 18         When assessed for the association between Vitamin D deficiency and clinical parameters, it was seen that there was a statistically significant difference between the Pulse rate (p=0.007), SPO2 (p=0.008), PaO2 (p=0.011), and SO2 (p=0.005) among the groups. Inflammatory markers like CRP, ferritin, LDH did not show any such significant difference. Concerning the Outcome of variables, though there was no significant association found between the groups, it was seen that majority i.e nearly 72% in whom mortality was the outcome, had lower levels of Vitamin D. Some retrospective studies have demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Maghbooli Z et al reported that Vitamin D sufficiency was associated with a statistically significant lower risk of hypoxia, defined by an arterial blood oxygen saturation level below 90%. The study also showed that in vitamin D sufficient patient’s serum CRP and blood lymphocyte percentage were significantly lower and higher respectively and there were no significant differences in hospitalization duration between patients with and without vitamin D sufficiency. 19 An Indonesian retrospective cohort study by Raharusun P et al has reported that vitamin D status is strongly associated with COVID-19 mortality outcome of cases after controlling for age, sex, and comorbidities. 12 In a report, Alipio M observes a significant association between vitamin D status and clinical outcomes (p 50 years and the females had lower vitamin D levels with significant statistical association seen only between sex and Vitamin D levels. We did not find any such significant difference in Inflammatory markers like CRP, ferritin, LDH between the groups. It was seen that the majority of COVID-19 patients in whom mortality was the outcome, had lower levels of Vitamin D but there was no significant association found between the groups for the outcome variables. Acknowledgement: Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed Conflict of interest: No conflict of interest to declare Funding: No funding was received Author contribution: Dr. Rajalakshmi R: Conception and design, acquisition, analysis, interpretation of data and drafting the manuscript Dr Akshay H M: Design, acquisition of data, interpretation of data and revising the manuscript critically for important intellectual content Dr Nagashree V: Design, analysis and interpretation of data and drafting of the manuscript Dr Smitha M C: Design, analysis and interpretation of data and drafting of the manuscript Dr Devaki K: Acquisition of data and analysis. Englishhttp://ijcrr.com/abstract.php?article_id=4148http://ijcrr.com/article_html.php?did=4148 Zhu N., Zhang D., Wang W., Li X., Yang B., et al . A novel coronavirus from patients with pneumonia in China, 2019. New Engl. J. Med. 2020;8:727–733. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it Huang C., Wang Y., Li X., Ren L., Zhao J., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;10223:497–506. Song P, Li W, Xie J, Hou Y, You C. Cytokine storm induced by SARS-CoV-2. Clin Chim Acta. 2020;509:280-287. DeLuca HF. Vitamin D: Historical Overview. Vitam Horm. 2016;100:1-20. Christakos S, Hewison M, Gardner DG, Wagner CL, Sergeev IN, et al. Acad Sci. 2013 May;1287(1):45-58. Adorini L. Intervention in autoimmunity: the potential of vitamin D receptor agonists. Cell Immunol. 2005 Feb;233(2):115-124. Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009 Feb 23;169(4):384-390. Martineau Adrian R, Jolliffe David A, Hooper Richard L, Greenberg Lauren, Aloia John F, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data Bri Med J. 2017 Feb; 356:i6583. Wei R, Christakos S. Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D. Nutr. 2015 Sep 24;7(10):8251-8260. Laird E, Rhodes J, Kenny RA. Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Ir Med J. 2020 May;113(5):81. Raharusun P, Priambada S, Budiarti C, Agung E, Budi C.  Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study. SSRN Elect J. 2020; 19(8): 312-316.. 10.2139/ssrn.3585561. Gunville CF, Mourani PM, Ginde AA. The role of vitamin D in the prevention and treatment of infection. Inflamm Allergy Drug Targets. 2013 Aug;12(4):239-245. Azizieh F, Alyahya KO, Raghupathy R. Association between levels of vitamin D and inflammatory markers in healthy women. J Inflamm Res. 2016 Apr 27;9:51-57. Hernández JL, Nan D, Fernandez-Ayala M, García-Unzueta M, Hernández-Hernández MA, et al. Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection. J Clin Endocrinol Metab. 2021 Mar 8;106(3): e1343-e1353 .Jain, A., Chaurasia, R., Sengar, N.S. et al. Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep.2020;10: 20191. Mosekilde L. Vitamin D and the elderly. Clin Endocrinol. 2005 Mar;62(3):265-281. Zhou F, Yu T, Du R, Fan G, Liu Y, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. Maghbooli Z, Sahraian MA, Ebrahimi M, Pazoki M, Kafan S, et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS ONE.2020 Sep;15(9): e0239799. Alipio M. Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-2019). SSRN Electr J .2020; 8(2): 211-215. 10.2139/ssrn.3571484. Aranow C. Vitamin D and the immune system. J Investig Med. 2011 Aug;59(6):881-886. Kota S, Kota Siva, Jammula S, Meher L, Panda S, et al. Renin-angiotensin system activity in vitamin D deficient, obese individuals with hypertension: An urban Indian study. Indian journal of endocrinology and metabolism. 2011 Oct;15 (4): 395-401.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareUtilization of Waste Leaves of Beta Vulgaris, Brassica Oleracea and Oryza sativa Flakes for the Development of Iron-rich Vermicelli English125129Singh RichaEnglish Sharma LuxitaEnglishIntroduction: Nutritional enhancement of traditional foods is gaining a lot of importance nowadays. Also, utilization of unexplored food items is being considered. It has been seen that intake of food prepared from the leaves has expanded, but some leaves like cauliflower greens and Beetroot greens have a higher waste ratio and are generally discarded. Aim: The study was conducted to utilize these leaves to formulate a product that is rich in iron and will be a better counterpart to the conventional product. Rice flakes were also used to increase the nutritional content of the product. Methods: Rice vermicelli was prepared by using iron-rich powder. The iron-rich powder was obtained by mixing powder of beet greens and cauliflower greens in the ratio of 50:50. Four variations of the product were prepared viz., Sample A, sample B, sample C and sample D with a 10g, 15g, 20g and 25g incorporation of iron-rich powder. Physico-chemical characteristic of the developed products was also determined like cooking loss, water absorption, swelling index etc. Sensory evaluation of the developed products was carried out using a 9-point hedonic scale. Results: Sample B i.e. 15g incorporation was found to be the most acceptable sample. Proximate analysis showed the iron content of the developed product to be 4.25mg/100g. Conclusion: The development of novel and nutritious food products can be carried out using unexplored and unutilized sources of vegetables. This will ensure valorization of the developed food product and also food & nutrition security. EnglishBeetroot leaves, Cauliflower greens, Iron-rich vermicelli, Gruel loss, Swelling index, Water absorption, Waste utilizationIntroduction: Several nutritional deficiencies are prevalent in the Indian subcontinent for a very long time. Since, the launch of various nutritional programmes and schemes for improving the nutritional status of the population, a lot have been achieved, but still, there is a lot left to be done. A large population of the country is still undernourished and suffers from Malnutrition. A comprehensive report of the Food and Agricultural Organization stated that 190.7 million people i.e. 14.5% people were undernourished during 2014- 2016.1 Major micronutrient deficiencies are mainly about Iron, Iodine and Vitamin A. Many nutritional deficiencies were the reason for 0.5% of the total deaths in the country in the year.2 This nutritional burden of hidden hunger is a major reason which also affects the country’s economic growth. According to Stein & Quaim, 2007 this malnourishment can cost up to 0.8 to 2.5 % of the country’s gross domestic product.3 Nutritional enhancement of already existing food products is being followed throughout the world. Some of these practices are quite conventional while some have been novel in their approach. Also as a means of ensuring nutritional security, exploitation of underutilized foods is gaining significance. This approach can be a benchmark to ensure per capita availability of food, hence safeguarding food security.4 As stated earlier, one of the major micronutrient deficiencies is that of Iron, which leads to Iron deficiency anaemia. Anaemia is a major nutritional problem that is ignored throughout the world, whether in developing or developed countries. The World Health Organization (WHO) defines anaemia as the condition where the haemoglobin (Hb) value is less than 13 g/dL in men, less than 12mg/dL in non-pregnant women, and less than 11 g/L in pregnant women. The major incidence of Iron deficiency can be manifested in growing children, women in the reproductive age group, pregnant women, the elderly and people suffering from chronic diseases.5 To combat this nutritional problem, several strategies have been formulated throughout the world, these include Oral/intravenous iron supplements, dietary education, nutritional awareness and food fortification. Out of all these, food fortification or Biofortification is the most promising and lasting approach which can enhance the micronutrient status amongst the beneficiaries.6 Thus, the food-based approach focuses on enhancing the nutritive value of an existing food product and can be carried out on a household level. The utilization of green leaves of cauliflower and beetroot for the development of Iron-rich vermicelli is the main endeavour with which this study is undertaken. Green vegetables are rich in nutrients and dietary fibre. They have fewer calories and fat but are excellent sources of vitamins like A, K, and C, carotenoids, folate, manganese. Cauliflower (Brassica oleracea) is a very common and easily available vegetable, which is consumed by one and all. According to a review article by Sagar et al., 2018, the global production of cauliflower and broccoli was about 24.17 million metric tonnes, which is humongous.7 Cauliflower greens fall in the category of leafy greens which have a higher proportion of Iron but these are generally discarded or either used for animal fodder.8,9 Apart from being highly nutritional as in terms of a good amount of Iron and Beta carotene, they also have a higher waste index, because these are generally discarded.10 Beetroot is also called Chukandar in Hindi. Its scientific name is Beta Vulgaris L. It is the taproot portion of the plant which is commonly consumed. It belongs to the family Chenopodiaceae. Beetroot leaves are also one of the most underutilized vegetables which are highly nutritious.11The iron content of Beetroot leaves is even better than that of spinach.12 It is being assumed that the nutritional composition of beet leaves is similar to the beetroot which is rich in carbohydrates, fibre, protein, and many minerals such as Sodium, Potassium, Calcium as well as Iron.13 Some of the phytonutrients present in beetroot includes polyphenols, carotenoids, Betacyanins, Betaxanthins, etc.14 Rice flakes are obtained from paddy and these are some of the very versatile ingredients which can be used in numerous ways. Some other names which it is known by are Poha, Aval, or Avalakki.15 It is considered to be a good source of iron owing to its production process, which requires the rice to be passed through iron rollers. This enables the flaked rice to retain some of the iron from the rollers.16 Hence, these can be used as a low-cost, easily available source of iron to fortify various food products. Vermicelli is a very commonly consumed extruded food product. It is traditionally prepared from whole or refined wheat flour, which is kneaded into a semi-hard dough. The prepared dough is either passed through an extruder and cold extrusion is carried out. Sometimes, the small pieces of dough are rolled using fingers and broken manually in the form of vermicelli. The formed vermicelli is laid out on sheets and sun-dried.17 Materials & Methods The present study was conducted in the Nutrition Lab of the Department of Dietetics & Applied Nutrition of Amity University Haryana, Gurgaon, India. Procurement and Processing of Ingredients Beetroot Leaves & Cauliflower Greens: Fresh beetroot leaves and Cauliflower along with greens were collected from the nearby vegetable market of Panchgaon, Haryana. Damages, wrinkled, yellow, and old leaves were discarded and only green undamaged medium-sized leaves were selected. The greens were removed from cauliflower and saved for further use. The cauliflower greens (Leaves and juicy stem) and also the beetroot leaves were washed under running tap water to remove any impurities from the surface. Washed leaves of beetroot were blanched for 2 minutes.  The blanching was carried out by putting leaves in hot boiling water for 2 minutes and then placing them in cold water immediately.  The blanched leaves were placed on an absorbent paper to remove excess moisture. After that, the leaves were sun-dried for 2 days. The cauliflower greens were cut into small pieces to ensure even drying under the sun. Sun-drying was carried out for 3 days. To ensure complete drying, the sundried beetroot leaves and cauliflower greens were further dried in a laboratory hot air oven at 60 °C. The dried beetroot leaves and cauliflower greens were powdered using a household grinder and passed through a sieve to ensure even texture. The prepared Beetroot leaves to powder and Cauliflower greens powder were mixed in equal quantities and stored in an airtight container which was labelled as an Iron-rich mix. Rice Flakes: Packaged rice flakes/poha was purchased from a nearby departmental store of Panchgaon, Haryana. The procured rice flakes were converted into a powdered form by grinding in the household grinder. The ground poha was passed through a sieve to obtain a flour-like consistency. Development of Iron-rich vermicelli: Refined wheat flour (Tricticum aestivum), rice flakes powder (Oryza sativa), Beetroot leaves powder (Beta vulgaris) and Cauliflower greens powder (Brassica oleracea) were used for the preparation of four variations of Iron-rich vermicelli viz. Sample A, B, C, and D. The four samples varied from each other based on their composition. The variation of ingredients used for the preparation of 4 samples is mentioned in table no. 1. All four ingredients were mixed and kneaded into a hard dough using an adequate amount of water. The prepared dough was passed through a household press and cold extruded into vermicelli and sundried subsequently. Physico- Chemical analysis of Iron-rich Vermicelli: The developed iron-rich vermicelli was subjected to proximate analysis for moisture, ash, fat, fibre, protein, carbohydrate, and Iron by AOAC methods.18 Sensory Evaluation: The developed iron-rich vermicelli was subjected to sensory evaluation by a 20 membered semi-trained panel of judges. All four variations were evaluated organoleptically for appearance, taste, texture, flavour, and overall acceptability using a 9-point hedonic scale.19 Cooking Quality: The developed iron-rich vermicelli was cooked in water until the inner core was softened. To ensure that the product is cooked, a strand of vermicelli was pressed between thumb and index finger. Solid Gruel Loss: Mestres et al., 1988 devised a method for determining Solid loss.20 Weighted sample of developed iron-rich vermicelli was cooked in an adequate amount of water. Once cooked, it was strained out and the remaining filtrate was transferred to a pre-weighed petri dish. The contents of the petri dish were evaporated overheated water bath and then kept in a laboratory hot air oven for an hour. The weight of the petri dish was again taken and solid gruel loss was calculated using the formula mentioned below: Here, the Weight of the sample taken for cooking is denoted as “W” The initial weight of the petri dish is denoted as W1 The final weight of the petri dish is denoted as W2 Water Absorption: It is the ratio between the weight of the cooked vermicelli to the weight of vermicelli in a raw uncooked state.21 weight of raw vermicelli Swelling Index: Cleary and Brennan, 2006 have instigated the method for determining the swelling index.22 To determine swelling index a weighted sample of vermicelli i.e. 10 g was cooked in 200 ml (20 times) of boiling water for 10 minutes over a water bath maintained at 100 °C. After cooking the excess water was decanted and the vermicelli was dried to remove extra moisture on a filter paper. The cooked sample was weighed. Here, the weight of the product before cooking is denoted by “W1” and weight of product after cooking is denoted by “W2” Results & Discussions Sensory Evaluation: All the four variations of the developed Iron-rich vermicelli were subjected to sensory evaluation by a 20 membered panel of semi-trained judges. Sensory scores of all the samples of the developed product are mentioned in Table no. 2. The sensory evaluation scores showed Sample B i.e. the one with 15 grams of Iron-rich powder as the most acceptable sample. Attributes like taste, mouthfeel, flavour and overall acceptability were found to be the highest in the case of Sample B. Highest score for appearance was given to Sample A, followed by Sample B, C, and D. Due to the addition of Iron-rich powder, the colour variation was seen which affected the appearance of the samples, higher quantities of Iron-rich powder imparted a dark colour to the samples which affected their appearance in both cooked and raw state. There were slight variations in the perception of taste in Samples A & B, while the other two samples i.e. C & D received fewer scores for taste from panel members. The addition of iron-rich powder imparted a peculiar mouthfeel to the developed product which was not found to be acceptable as the quantity of Iron-rich powder increased. However, it did not have much effect on the flavour of the product, which is quite evident from almost similar scores for Sample A, B, and C. Therefore, sensory evaluation scores of the developed product showed the incorporation level up to 15% to be acceptable by the panel members. Nutrient Composition: The proximate analysis was also carried out. In this study, the nutrient composition of the most acceptable product i.e. Sample B was done using standard techniques. The iron content of the developed and most acceptable product is 4.25 mg/100g, which is approximately 23 % of the daily iron requirements. The addition of green leafy vegetables in the cooked product can also help in enhancing the iron content and also ensure increased bioavailability. Table no. 3 shows the nutritional composition of the most acceptable sample i.e. Sample B. Cooking Loss/Solid Gruel Loss: Gruel loss can be defined as the number of dissolved solids in the cooking water. It is an indicator of the structural integrity of the developed product.23 Higher gruel loss will indicate a poor cooking performance for the vermicelli. The structural integrity of the product is directly dependent upon the raw materials used. According to Krishnan et al., 2012 a dense structure will result in lower cooking loss and hence a better product.24 Addition of refined flour provided greater stability to the structure of vermicelli due to the presence of gluten and hence gave a stable structure to the product which also contained rice flakes and powdered leaves. It can be observed from the result that the cooking loss increased with an increase in the amount of Iron-rich powder. Sample D showed the highest cooking loss while the most acceptable variant i.e. Sample B showed a gruelling loss of 10.6%. Water absorption: This characteristic is also an important measure of cooking quality. As per the results tabulated in Table no. 4, it can be seen that there are only slight variations in the values of water absorption in the case of all four samples. However, it can also be observed that with an increase in the content of iron-rich powder, the water absorption also increases. Similar studies have also reported an increase in water absorption with the addition of carrot powder.25 Swelling Index: These values showed a downward trend with increased content of the iron-rich powder. This may be attributed to the relationship between starch and fibre. An increase in the amount of fibre can lower the swelling of starch granules and lower swelling indices. But the Samples A, B, and C shower slight variations in the swelling index. The lowest values are recorded in the case of Sample D. A study conducted by Padalino et al., 2017 also indicated a lower swelling index with the amount of tomato peel powder in developed spaghetti.26 All the tests about the cooking quality of the developed Iron-rich vermicelli have been tabulated in Table no. 4. Conclusion It can be concluded from the present study that dried leaf powder of beetroot and cauliflower, which are generally discarded and have a higher waste ratio. These green leave are nutrient-dense but seldom find a place in the diet of people due to ignorance and lack of awareness. In this study, these have been utilized for enhancing the nutrient content of the developed vermicelli, which is much higher than its conventional counterpart. Keeping the same aim of nutritional enhancement in mind, rice flakes powder has also been incorporated for further value enhancement. This study is also one of the food-based strategies for tackling nutrient (Iron) deficiency. Hence, through this study, an effort has been made to boost nutrition and food security. Acknowledgements We acknowledge Amity University Haryana for supporting and providing Labs and other facilities for the research activity in the Department of Dietetics and Applied Nutrition. Conflict of Interest There is no conflict of interest. Source of Funding NIL Individual Author&#39;s Contribution All work related to the literature review, product development, testing of the product has been carried out by both the authors jointly. The manuscript is also written jointly. Englishhttp://ijcrr.com/abstract.php?article_id=4149http://ijcrr.com/article_html.php?did=4149 FAO, IFAD, UNICEF, WFP and WHO, The State of Food Security and Nutrition in the World. 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Sagar NA., Fruit and Vegetable waste: Bioactive compounds, Their extraction, and Possible Utilization. Compr rev food sci f. 2018; 17: 512-531. Boer K, Pandey A. “India’s Sleeping Giant: Food”, McKinsey Q. 1997; 83(1). Ambika Chauhan, Int J Nutr Agric Res. 2014; 1(2): 93 - 98. Kowsalya, S, Sangheetha, M. Acceptability and nutrient profile of cauliflower leaves (Brassica oleraceae var. Botrytis). Indian J Nutr Diet. 1999; 36: 332-338. BiondoP.B.F, Evaluation of beetroot (Beta vulgaris L.) leaves during its developmental stages: a chemical composition study. Food Sci Technol (Campinas). 2013; 34(1): 94-101. Joshi, P, Mathur, B. Preparation of value-added products from the leaf powders of dehydrated less utilized green leafy vegetables. J. Hortic. For. 2010; 2(9): 223 – 228. Ninfali P., Nutritional and functional potential of Beta vulgaris cicla and rubra. Fitoterapia. 2013; 89: 188-199. Strack, D., Vogt, T, Schliemann, W. Recent advances in betalain research. Phytochemistry. 2003; 62(3): 247–269. Deepa C., Singh V. Nutrient changes and functional properties of rice flakes prepared in a small scale industry. Oryza 2011; 48 (1): 56-63. https://www.krishisewa.com/articles/pht/999-production-technique-of-paddy-s-value-added-product-poha-or-flaked-rice.html. Accessed on 15. 2. 2021. Mogra R.; Midha S. Value addition of traditional wheat flour Vermicelli. J Food Sci Technol. 2013; 50(4): 815–820. A.O.A.C. Official Methods of Analysis. Association of Analytical Chemists, Washington, DC. 2005; 18. Swaminathan M, Food science, chemistry, and experimental foods. Bangalore Printing and Publishing Co. Ltd., Bangalore. 1987. Mestres C, Colonna P, Bullion A. Characteristics of starch networks within rice flour noodles and mung bean starch vermicelli. J Food Sci. 1998; 53: 1809-1812. AACC. Approved methods of the American Association of cereal chemists. St Paul Minnesota. 2005. Cleary, L, Brennan, C. The influence of (1→3) (1→4) β glucan rich fraction from barley on the physicochemical properties and in vitro reducing sugars release of durum wheat pasta. Int. J. Food Sci. Technol. 2006; 41:910-918. Li. P., Lu, W., Hseih, Ch. Li. T., Huang D. Rheological properties of dough and quality of slated noodles supplemented with djulis flour. J. Agric. Sci. 2015; 7(6): 84-92. Krishnan, J.G., Menon, R., Padmaja, G., Sanjeev, M.S, Moorthy, S.N. Evaluation of nutritional and physicochemical characteristics of dietary fibre enriched sweet potato pasta. Eur. Food Res. Technol. 2012; 234(3): 467-476. Kohajdová Z., Karovi?ová J., Jurasová M. Influence of carrot pomace powder on the rheological characteristics of wheat flour dough and wheat rolls quality. Acta Sci. Pol. Technol. Aliment. 2012; 11: 381–387. Paulino, Lucia, Functional pasta with tomato by-products as a source of antioxidant compounds and dietary fiber. Czech J. Food Sci. 2017; 35(1): 48-56.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareCorrelation of Early Childhood Caries with Maternal Risk Factors among 2-6 Years Old Children in Vijayawada City, Andhra Pradesh, India - A Cross-Sectional Study English130136M. Sai DivyaEnglish S. Srikanth RajuEnglish P. GowthamEnglishIntroduction: Maternal risk factors play a vital role in the transmission of infection to the child. Hence this study was undertaken to evaluate the extent of influence of maternal risk factors exert on ECC below 6 -year-old children. Materials and Methods: A single calibrated examiner performed all clinical examinations under natural light using a mouth mirror and probe. The study was conducted in a random sample of 140 mother children pairs. Data related to pregnancy-related issues, feeding methods, oral hygiene measures and dental knowledge & practices was obtained. The data was then tabulated and statistically analyzed. Results: Out of the 140 samples, 103 (73.57%) children had ECC of which 5-6 year children were more prevalent (84%). Children brushing twice daily had significantly less ECC (pEnglish Mother, ECC, Children, Risk factors, Feeding methods, Oral hygiene measuresINTRODUCTION:  Dental caries in infants and children has been recognized as a perennial health problem ever since an American physician named Abraham Jacobi first observed and described the problem in 1862 in one of his children.1   Beltrami, in 1932 named it as “Les dentesnoires des tout-petits” implying “black teeth of the very young.1 The term  ‘Early Childhood Caries (ECC) was suggested at a workshop held by the Centers for Disease Control and Prevention and a case definition was proposed using patterns of caries experience as defining criteria at a workshop convened by the National Institutes of Health (NIH) 1999. 2, 3 ECC has a complex, multifactorial aetiology where cariogenic organisms under the influence of fermentable carbohydrates induce caries in a susceptible host over some time. The cariogenic organisms implicated in ECC include mutans streptococci (MS) and Lactobacillus species. Maternal risk factors like infant feeding practices such as frequent exposure to sugar, frequent snacking, taking sweetened drinks during bedtime, and sharing foods with adults, oral hygiene, dietary habits, socioeconomic status and education level also have a bearing on the establishment of high MS counts in children.4,5  Since, maternal risk factors play a vital role in the transmission of infection to the child, the need of the hour is to thoroughly understand and evaluate their role in the disease process. Hence this study was undertaken to evaluate the extent of influence of maternal risk factors exert on ECC below 6 -year-old children. MATERIALS AND METHODS: Study design: This is a Randomized clinical trial study approved by the ethical committee of Drs Sudha and Nageswararao Siddhartha Institute of Dental Sciences, Gannavaram Mandal, A.P with an ethical clearance number. O.C.No/IEC/25/2015. Patient selection: The study was conducted in a random sample of 140 mother children pairs who reported to the Department of Pedodontics and Preventive Dentistry, DrsSudha and Nageswararao Siddhartha Institute of Dental Sciences, Gannavaram Mandal, A.P and Department of Paediatrics, Siddhartha Medical College, Vijayawada, A.P. Mothers were explained about the study and written consent was obtained from them Inclusion criteria: Children with ages between 12-71 months (as per the ECC definition by the AAPD- 2014) diagnosed with ECC along with their mothers Children who did not have any systemic ailments. Exclusion criteria: Children who belong to the 12 -71 months age group and lost their mothers Children who belong to the 12 -71 months age group whose mothers were not residing with them. Children and mothers with systemic diseases, congenital syndromes & dental developmental disorders A structured questionnaire by Winter et al., modified according to Indian conditions was used in this study. This questionnaire containing questions related to pregnancy-related issues, feeding methods, oral hygiene measures and dental knowledge & practices was explained by the examiner to the mothers in the language of their understanding and sufficient time was given for answering. The answers were filled in by the examiner only.  The obtained data were tabulated by using Excel (Microsoft). The completed proformas were statistically analyzed to find the correlation between ECC and maternal caries, oral hygiene and risk factors. Descriptive statistical analysis was carried out in the present study. Results were represented as mean ± SD (Min-Max) and categorical measurements were presented as percentages using SPSS- software (version 20). A Chi-square test was used to compare qualitative data. RESULTS: Out of the 140 samples, 103 (73.57%) children had ECC of which 5-6 year children were more prevalent (84%). The survey of brushing habits revealed 97% of the sample populations were using toothbrushes and the majority of them (96%) were brushing only ones. Children brushing twice daily had significantly less ECC (pEnglishhttp://ijcrr.com/abstract.php?article_id=4150http://ijcrr.com/article_html.php?did=4150 Borutta A, Wagner M, Kneist S. Early Childhood caries: A multifactorial disease. OHDMBSC 2010; 9:32-8. Kaste LM, Gift HC. Inappropriate infant bottle-feeding status of the healthy people 2000 objective. Arch PediatrAdolesc Med 1995; 149:786-91. Drury TF, Horowitz AM, Ismail AI, Maertens MP, Rozier RG, Selwitz RH.et al. Diagnosing and reporting Early Childhood Caries for research purposes. A report of a workshop sponsored by the National Institute of Dental and Craniofacial Research, the Health Resources and Services Administration, and the Health Care Financing Administration. J Public Health Dent 1999; 59:192-7. Vadiakas G. Case definition, aetiology and risk assessment of early childhood caries (ECC): a revisited review. Eur Arch Paediatr Dent 2008; 9:115-25. Kawashita Y. Dental caries in 3-year-old children are associated more with Child Rearing Behaviors than Mother-Related Health Behaviors. J Public Health Dent 2009; 69:104-10. Macentee M, Harrison R, Wyatt C. Strategies to Enhance the Oral Health of British Columbians, specifically  Aboriginal Peoples,  Tobacco-Users,  and those of  Low Socioeconomic Background. 2001; 8-14. Holm A-K. Caries in the preschool-child - international trends. J Dent 1990; 18:291-5. Conry JP, Messer LB, Boraas JC, Aeppli DP, Bouchard TJ Jr. Dental caries and treatment characteristics in human twins reared apart. Arch Oral Biol 1993; 38:937-43. Watt R G. Emerging theories into the social determinants of the health: implications for oral health promotion. Community Dent Oral Epidemiol 2002; 30:241-7.  Finlayson TL, Siefert K, Ismail AI, Sohn W. Psychosocial factors and early childhood caries among low-income African-American children in Detroit. Community Dent Oral Epidemiol 2007; 35:439-48.  Shearer DM, Thomson WM. Intergenerational continuity in oral health: a review. Community Dent Oral Epidemiol 2010; 38:479-86. ThitasomakulS, Piwat S, Thearmontree A, Chankanka O, Pithpornchaiyakul W, Madyusoh S.et al. Risks for early childhood caries analyzed by negative binomial models. J Dent Res. 2009; 88:137-41. Rosenblatt A, Zarzar P. Breast-feeding and early childhood caries: an assessment among Brazilian infants. Int J Pediatr Dent. 2004; 14:439–45. Serwing JR, Mungo R, Negrete VF, Duggan AK, Korsch BM. Child-rearing practices and nursing caries. Paediatrics. 1993; 92:233-237. Ramos-Gomez FJ, Tomar SL, Ellison J, Artiga N, Sintes J, Vicuna G.et al. Assessment of Early Childhood Caries and dietary habits in a population of migrant Hispanic children in Stockton, California. J Dent Child. 1999; 66:395-403. Avila WM, Pordeus IA, Paiva SM, Martins CC. Breast and Bottle Feeding as Risk Factors for Dental Caries: A Systematic Review and Meta-Analysis. PLoS One. 2015; 10:e0142922. Febres C, Echeverri EA, Keene HJ. Parental awareness, habits, and social factors and their relationship to baby bottle tooth decay. Pediatr Dent. 1997; 19:22-27. Azevedo TD, Bezerra AC, de Toledo OA. Feeding Habits and Severe Early Childhood Caries (S-ECC) in Brazilian Preschool Children. Pediatr Dent. 2005; 27(1):28-33. Dini EL, Holt RD, Bedi R. Caries and its association with infant feeding and oral health-related behaviours in 3–4-year-old Brazilian children. Community Dent Oral Epidemiol 2000; 28:241-8. Hattab FN, AI-Omari MA, Angmar-Mansson B, Daoud N. The Prevalence of Nursing Caries in One-to-Four-Year-Old Children in Jordan. ASDC J Dent Child 1999; 66:53-8. Shantinath SD, Breiger D, Williams BJ. The relationship of sleep problems and sleep-associated feeding to nursing caries. Pediatr Dent 1996; 18:375-8. Feldens CA, Giugliani ER, Vigo A, Vitolo MR. Early feeding practices and severe early childhood caries in four-year-old children from southern Brazil: A birth cohort study. Caries Res 2010; 44:445-52. Ollila P,Lamas M. A seven-year survival analysis of caries onset in primary second molars and permanent first molars in different caries risk groups determined at age two years. ActaOdontologicaScandinavica  2007; 65:29-35. World Health Organisation (WHO). Global strategy for infant and young child feeding. Geneva: WHO 2003. De Menezes VA, Cavalcanti G, Mora C, Garcia AFG, Leal RB. Pediatric medicines and their relationship to dental caries. Braz J Pharm Sci. 2010; 46:157-64. Marrs JA, Trumbley S, Malik G. early childhood caries: determining the risk factors and assessing the prevention strategies for nursing intervention. Pediatr Nurs. 2011; 37:9-15. Winter GB, Rule DC, Mailer GP, James PM, Gordon PH. The prevalence of dental caries in pre-school children aged 1 to 4 years. Br Dent J. 1971; 130:434-6. Ribeiro NM, Ribeiro MA. Breastfeeding and early childhood caries: a critical review. J Pediatr. 2004; 80:199-210 Oral health in America: a report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service, National Institute of Dental and Craniofacial Research. 2000 American Academy of Pediatric Dentistry, Reference manual. Pediatr Dent. 2003; 25:1-150.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareDevelopment and Validation of Reverse Phase Chiral HPLC Method for Quantification of Enantiomer in Lamivudine Drug Substance English137141Siva Jyothi NEnglish Venkatnarayana MEnglishIntroduction: Chiral HPLC is a chromatographic separation technique used to separate the Enantiomer or Diastereomer from the main active compound. Aim: A simple, rapid and robust reverse phase chiral HPLC method was developed and validated for the quantification of Lamivudine Enantiomer in Lamivudine drug substance. Methodology: The Enantiomer of Lamivudine was resolved in Lux cellulose-5 column using a mobile phase containing Methanol: Diethylamine (100:0.1 v/v) at a flow rate of 0.5 mL/min. Results: The resolution between Enantiomer and Lamivudine was found to be more than 1.5 in an optimized method. The developed method was validated and proved that the method was specific, sensitive, accurate and precise as per ICH. The limit of detection and limit of quantification for Lamivudine Enantiomer was 0.004% and 0.012% respectively. The linearity curve was found to be linear and the correlation coefficient obtained was 0.999. The average percentage recoveries of Enantiomer were in the range of 97 to 102%. Conclusion: The proposed method was found to be suitable and accurate for the quantitative determination of Enantiomer in Lamivudine drug substance. EnglishEnantiomer, Lamivudine, Reverse phase chiral HPLC, Lux cellulose-5 column, Sensitivity, Method development, Method validation, ICH guidelinesINTRODUCTION Lamivudine is a reverse transcriptase inhibitor and zalcitabine analogue in which a sulfur atom replaces the 3&#39; carbon of the pentose ring. It is used to treat Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV).1 Lamivudine is chemically known as 4-Amino-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydro pyrimidine-2-one, Its molecular formula C8H11N8O3S and the molecular weight is 229.3 gm/mol.1 Lamivudine is generally called 3TC and is available as Epivir® and Epivir-HBV® as individual and available with the combination of drug Tenofovir.2 Lamivudine is an approved medicine by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults and children 3 months of age and older. Lamivudine belongs to a group of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs block an HIV enzyme called reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.3 Lamivudine and Enantiomer structures are shown in Figure 1. The separation of Enantiomer has become very important in analytical chemistry especially in the pharmaceutical industry. In the literature survey, various methods are available for the determination of Lamivudine in combined dosage form quantification methods.4-,9 An HPLC method was published with 0.3% of specification limit for the separation of Enantiomer in Lamivudine by using L45 column with 5µm to 10µm diameter column.10 In this method resolution between Enantiomer and Lamivudine peak was less. Another research paper was available for Lamivudine Enantiomer published with long runtime by using chiral HPLC.11 In this research work, a reverse phase chiral HPLC method was developed for resolving Enantiomer by considering 0.05% as specification limit along with short run time and validated the method according to ICH guidelines.12,13 MATERIALS AND METHODS Lamivudine drug substance and related impurities were supplied by Synzeal laboratory limited. The HPLC grade methanol and Diethylamine procured from Merck chemicals limited. Instrumentation and Chromatographic conditions WATERS HPLC, Model: 2695 equipped with 2996 photodiode array detector with an automated sample injector was used for development and method validation, Lux cellulose-5, 250x 4.6 mm, 5µm column was used for the separation. 0.1% Diethylamine in methanol used as mobile phase as well as diluent. Analysis was carried out as isocratic mode with a flow rate of 0.5 mL/min and the injection volume was 10µL. The column temperature was 30°C and the run time was 12 minutes. The data were acquired at 270 nm. The output signal was monitored and integrated using Empower 2 software. Sample solution Preparation Weighed and transferred 25 mg of Lamivudine sample into 100 mL volumetric flask, dissolved in 30 mL of diluent by sonication and makeup to the volume with diluent, containing solution concentration was 0.25 mg/mL. Enantiomer solution preparation (0.05%) Stock Solution-1: 5mg of Enantiomer was weighed and transferred to 50mL of volumetric flask and dissolved in 20 mL of diluent by sonication and made up to mark with diluents to give a stock solution-1 containing 0.1 mg/mL. Stock Solution-2:Transferred 1mL of stock solution-1 into a 10 mL volumetric flask diluted the volume with diluent to give a solution containing 10 µg/mL of Enantiomer. System suitability solution Preparation Weighed and transferred 25 mg of Lamivudine sample into 100 mL volumetric flask dissolved in 50 mL of diluent by sonication, add 1.25 mL of Enantiomer stock solution-2 and made up to the volume with a diluent solution containing a concentration of 0.25 mg/mL of Lamivudine and 0.000125 mg/mL of Enantiomer. Method Validation Specificity (Selectivity) Specificity is the ability to assess unequivocally the analyte in the presence of components that may be expected to be present in the impurities. There must be inarguable data for a method to be specific. Specificity measures only the desired component without interference from other species which might be present. The blank, system suitability solution and sample solutions were prepared as per methodology. Individual impurities prepared at 0.1 mg/mL and spike sample solutions have been made concerning specification limits. The retention time of all the injected analytes was recorded. Sensitivity The Limit of Detection is the minimum level at which the analyte can be reliably detected. The limit of quantitation is defined as the lowest amount or concentration of a drug substance which can be estimated with reproducible precision and accuracy under the optimized method conditions. LOD and LOQ were assessed by using the equations (1) and (2), respectively. LOD = 3.3 σ /S ………. (1) LOQ =10 σ /S ………..  (2)                      Where,                      σ = the standard deviation of the response (STEYX)               S = the slope of the calibration curve         The slope S is estimated from the calibration curve of the analyte. Linearity The linearity of the method was demonstrated for Lamivudine and Enantiomer by analyzing the solutions ranging from LOQ to 150% of the specification limit. The correlation coefficient for Enantiomer and Lamivudine was assessed. Precision Precision at LOQ The precision at LOQ level was confirmed by assessing the %RSD of peak areas of the six repeated injections of Lamivudine and Enantiomer solution having LOQ level concentration. System Precision The system precision of the current method was performed by injecting 100% level of Lamivudine standard solution in six replicates. Method Precision The precision of the method was determined by analyzing six individual samples of Lamivudine spiked with Enantiomer at 100% of the specification limit. Accuracy The accuracy of the method was determined percentage recovery method, using solutions containing Lamivudine sample spiked with Enantiomer at LOQ, 50%, 100% and 150% of the working strength of Lamivudine. All the solutions were prepared in triplicate and analyzed. Robustness It was determined by slightly changing the chromatographic method conditions intentionally. The robustness of the present method was evaluated by making the intentional changes to flow rate (±10%), column oven temperature (±5°C) and wavelength (±3nm) of the actual method conditions. RESULTS Optimization method Lamivudine and its Enantiomer were effectively separated by a method consisting of a Lux cellulose-5 (250x 4.6 mm, 5µm) column and. 0.1% Diethyl amine in methanol as a mobile phase which pumping in isocratic mode with a flow rate of 0.5 mL/min. The eluents were detected at 270nm wavelength. The retention time of Lamivudine and its Enantiomer were observed at 7.8min and 7.2 min respectively with acceptable resolution.  The chromatogram is shown in Figure 2. Method Validation Specificity (Selectivity) Based on the obtained results, all impurities eluted at different retention times and adequately resolved each other and also from main peak. Representative chromatogram was shown in Figure 3. Hence method has good specificity as per ICH guidelines. Sensitivity The LOD and LOQ values of Lamivudine and its Enantiomer were calculated as 0.0001mg/mL and 0.004mg/mL respectively for both analytes. Linearity The correlation coefficient (R2) obtained from the linear graph between concentration and peak area was found to be 0.999 for both Lamivudine and its Enantiomer (Table-1, Figure-4) which indicates good linearity of the method for the given range of concentrations. Precision The precision at LOQ and system precision of the method were assured by assessment of % RSD values of six replicate injections of Lamivudine and Enantiomer solution at LOQ level and 100 level specifications. Method precision of the method was assured by assessment % RSD value for the obtained % assay values of the six individual samples of Lamivudine spiked with Enantiomer at 100% of the specification limit. The Results (Table-2) represents that the method has adoptable precision as of ICH specifications. Accuracy The percentage recovery of the Enantiomer in spiked Lamivudine sample at LOQ, 50%, 100% and 150% of the working strength of Lamivudine was found to be 100±2 % and %RSD observed to be less than 2 (Table 3). Robustness There was no significant change observed in system suitability like relative retention time (RRT) and Resolution by changing flow rate, temperature, and wavelength (Table 4). Hence the method is said to be robust. DISCUSSION Proficient and broad searching of the literature reveals that only two HPLC methods have been reported for the determination of Enantiomer in Lamivudine drug substance. Due to long run time with low sensitivity of the reported HPLC methods, which should not be expressed as cost-effective method. To overcome the drawbacks of those HPLC methods, a proficient HPLC method should be required. In the present method, the run time and retention time of the Enantiomer and Lamivudine were low with Lux cellulose-5 (250x 4.6 mm, 5µm) and a mobile phase of 0.1% Diethyl amine in methanol at a flow rate of 0.5mL/min. The present method was economical in comparison with already existed HPLC methods less retention time and a simple mobile phase. The outcomes of the validation parameters were confirmed that the projected method has great accuracy, best specificity, and reproducible precision with exceptional sensitivity. CONCLUSION The newly developed method was very effective in the simultaneous estimation of Lamivudine Enantiomer. The results ensure that the method was simple, precise, and accurate. In comparison with the reported method, it has the advantage of high resolution and shorter retention time which makes the method is more acceptable and cost-effective. Hence it can be effectively applied for routine analysis in research institutions, quality control departments in industries, approved testing laboratories. ACKNOWLEDGEMENTS The authors are thankful to the Department of Chemistry, GITAM University, Hyderabad, India for encouragement. CONFLICT OF INTEREST The authors declare that there is no conflict of interest regarding the publication of this article. FUNDING:  It is self-financed, no funding was sponsored from any organization, funding agency and non -profit research bodies. AUTHORS&#39; CONTRIBUTIONS: Ms. Siva Jyothi. N has generated the research activity and prepared the manuscript. Dr. Venkatnarayana.M has given guidance and supervision to carry out this research work. LIST OF ABBREVIATIONS RT:  Retention Time LOD:  Limit of Detection LOQ:  Limit of Quantification ICH: International Conference on Harmonization SD:  Standard Deviation RSD:  Relative Standard Deviation RRT:  Relative retention Time Englishhttp://ijcrr.com/abstract.php?article_id=4151http://ijcrr.com/article_html.php?did=4151 Luo A, Jiang X and Ren H. Lamivudine therapy for chronic hepatitis B in children: a meta-analysis. Virol J. 2019;16(1):88. Luo A, Jiang X, and Ren H. Lamivudine plus tenofovir combination therapy versus lamivudine monotherapy for HBV/HIV coinfection: A meta-analysis. Virol J. 2018;15(1):139. Quercia R, Perno C-F, Koteff J, Moore K, McCoig C, Clair M et al. Twenty-Five Years of Lamivudine: Current and Future Use for the Treatment of HIV-1 Infection. J Acquir Immune Defic Syndr. 2018;78(2):125–135. Mallikarjuna RN, Gowri SD. Development and validation of stability-indicating HPLC method for simultaneous determination of Lamivudine, Tenofovir, and Dolutegravir in bulk and their tablet dosage form. Future J Pharm Sci. 2015; 1(2):73–77. Bhavsar DS, Patel BN, and Patel CN. RP-HPLC method for simultaneous estimation of tenofovir disoproxil fumarate, lamivudine, and efavirenz in the combined tablet dosage form. Pharm Meth. 2012; 3(2):73–78. Karishma S, Subramaniam S, Muthuraman M and Sivasubramanian A. RP-HPLC analytical method development and validation for lamivudine and zidovudine in pharmaceutical dosage forms. Int J Pharmtech Res. 2013; 5:1321–1331. Nalini CN, Nithya A, Afreen A, Banu AA, Hemalatha P and Gayathri EJ. Analytical Methods for Determination of Lamivudine and their Applicability in Biological Studies. Research J Pharm and Tech. 2018; 11(11):5166-172. Godela R and Sowjanya G. An effective stability indicating RP-HPLC method for simultaneous estimation of Dolutegravir and Lamivudine in bulk and their tablet dosage form. Future J Pharm Sci. 2020; 6:1-9. Nekkala K, Kumar VS and Ramachandran D. Development and Validation for the Simultaneous Estimation of Lamivudine, Tenofovir Disproxil and Dolutegravir In Drug Product by RP-HPLC. J Pharm Sci Res. 2017 Sep 1; 9(9):1505. Nandi U, Das A, Roy B, Choudhury H, Gorain B and Pal TK. Development and validation of an HPLC-UV method for simultaneous determination of zidovudine, lamivudine, and nevirapine in human plasma and its application to a pharmacokinetic study in human volunteers. Drug Test Anal. 2013;5(6):485–91. Subbarao M, Ramakrishna M and Mogilireddy D.  Chiral separation of lamivudine enantiomer by HPLC using cellulose tris (3,5-dichlorophenylcarbamate) as a chiral stationary phase.  Indo Am J Pharm. 2016; 6(5). The International Conference on Harmonization, Q2 (R1), (2005). https://www.ich.org/page/quality-guidelines The International Conference on Harmonization, Q1 (A) R2, (2003). https://www.ich.org/page/quality-guidelines

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareA Cross-Sectional Study to Analyse the Severity of Smoking and its Effects on Copd Patient&#39;s Bone Mineral Density English142148Mani SathishkumarEnglish Gayathri GaneshEnglish Giridharan SwethaEnglish Gangadharan VadiveluEnglishIntroduction: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in adults and currently represents the fourth leading cause of death in world1COPD it is recognized as a multi-component disorder, associated with systemic inflammation and extrapulmonary manifestation. Of which osteoporosis and osteopenia in COPD are a significant extra-pulmonary component which is least considered.3 Objective: The main aim of the study is to access the severity of COPD with Bone Mineral Density(BMD) which defines osteoporosis and osteopenia, along with serum CRP and Serum Calcium levels. We collected about 60 Spirometry proven COPD patient’s data and analysed using student t and Pearson chi-square test. Results: Observed majority of the study population was in the moderate to severe COPD group, of the moderate COPD group majority were osteopenic, severe COPD patients were osteoporotic. Conclusion: Lower the BMI the risk of developing low BMD increases, as the study shows patients with low BMI was mostly in the osteoporotic range. Serum calcium, CRP and Smoking status also were correlating with BMD levels. English COPD, BMD, Smoking, Spirometry, Serum calcium, DyspneaINTRODUCTION Chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. 2 Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases. 4 COPD has classically been considered to be restricted to pulmonary inflammation and structural remodelling. However, COPD is recognized as a multi-component disorder, associated with systemic inflammation and extrapulmonary manifestation7 The systemic aspects of COPD include oxidative stress and altered circulating levels of inflammatory mediators and acute-phase proteins.5 Local inflammation of the airways and lung parenchyma has always been acknowledged as part of the COPD disease process; however, it is becoming clear that the inflammatory response is systemic.9 In our study we analysed the effect of Systemic inflammation of COPD in the bone mineral density with serum calcium and serum CRP levels to get to know the extent of its impact. AIMS AND OBJECTIVES               To assess the level of BMD in COPD patients using quantitative ultrasound bone densitometer. To correlate the severity of COPD with airway obstruction (GOLD guidelines) and BMD. To assess BMI of COPD patients and its correlation with BMD. To assess serum CRP levels, Serum Calcium levels in COPD patients and their correlation with BMD. MATERIALS AND METHODS In the Department of Respiratory Medicine, Saveetha Medical College & Hospital, Chennai, Tamilnadu. Institutional Ethical Committee approval was obtained. STUDY DESIGN- Prospective, Cross-sectional design PERIOD OF STUDY September 2019 to April 2020 SAMPLE SIZE Cases: 60 INCLUSION CRITERIA All patients clinically and spirometrically diagnosed with COPD as suggested by GOLD guidelines. EXCLUSION CRITERIA Spirometry has proven bronchial asthma, COPD with other co-existing lung diseases like Treated Pulmonary Tuberculosis, Bronchiectasis, etc., Patients on long term steroids, Co-morbidities ( DM, SHT, Liver disorders) Cardiac conditions (Recent MI, Unstable Angina, CCF). STUDY PROTOCOL A total of 60 patients who were clinically proven COPD, attended to our outpatient department at Saveetha Medical College Hospital were enrolled in the study after getting their written and oral consent.         The patients with the following diagnostic criteria (according to the GOLD guidelines) were defined as having COPD Presence of cough and sputum production for at least 3 months in each of the two consecutive years, Exertional dyspnoea Clinical& Physical examination showing, Signs of airflow limitation like prolonged expiration and expiratory wheeze which is not fully reversible and with Signs of hyperinflation Investigations show Chest X-ray showing emphysematous change or chronic bronchitis picture, Spirometry showing post-bronchodilator FEV1/FVC ratio Englishhttp://ijcrr.com/abstract.php?article_id=4152http://ijcrr.com/article_html.php?did=4152 Agusti AG, Noguera A, Sauleda J. Systemic effects of chronic obstructive pulmonary disease. Eur Respir J. 2003;21(2):347- 60. Al-Fayez SF, Salleh M, Ardawi M, AZahran FM. Effects of sheesha and cigarette smoking on pulmonary function of Saudi males and females. Trop Geogr Med. 1988;40(2):115-23. American Thoracic Society. Chronic bronchitis, asthma and pulmonary emphysema: a statement by the Committee on Diagnostic Standards for Nontuberculous Respiratory Diseases. Am Rev Respir Dis. 1962; 85: 762–768. American Thoracic Society and European Thoracic Society. Skeletal muscle dysfunction in chronic obstructive disease. Am J RespirCrit Care Med. 1999; 159: Suppl. 4, 1–40 Anthonisen NR, Wright EC, Hodgkin JE. Prognosis in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1986;133:   14-20. Anto JM, Vermeire P, Vestbo J, Sunyer J. Epidemiology of chronic obstructive pulmonary disease. Eur Respir J. 2001; 17: 982–994. Badham C. An essay on bronchitis: with a supplement containing remarks on the simple pulmonary abscess. 2nd ed. London: J Callow. 1814. Balmes J, Becklake M, Blanc P, Henneberger P, Kreiss K, Mapp C, et al.American Thoracic Society Statement: Occupational contribution to the burden of airway disease. Am J RespirCrit Care Med. 2003;167(5):787-97. Barker DJ, Godfrey KM, Fall C, Osmond C, Winter PD, Shaheen SO et al. Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease. Bri Med J. 1991;303(6804):671-5. Biernacki W, Flenley DC, Muir AL, MacNee W. Pulmonary hypertension and right ventricular function in patients with COPD. Chest. 1988; 94: 1169–1175. Bikle DD, Halloran B, Fong L, Steinbach L, Shellito J. Elevated 1,25- dihydroxy vitamin D levels in patients with chronic obstructive pulmonary disease treated with prednisone. J Clin Endocrinol Metab. 1993; 76(2):456-461. Blanco I, de Serres FJ, Fernandez-Bustillo E, Lara B, Miravitlles M. Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha1 antitrypsin deficiency in European countries. Eur Respir J. 2006; 27(1):77. Bon JM, Zhang Y, Duncan SR, Pilewski JM, Zaldonis D, Zeevi A et al. Plasma inflammatory mediators associated with bone metabolism in COPD. J Cron Obstruct Pulmon Dis. 2010; 7:186-191. . Bolton CE, Ionescu AA, Shiels KM, Pettit RJ, Edwards PH, Stone MD et al. Associated loss of fat-free mass and bone mineral density in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004; 170(12):1286-1293. B. Parthasarathi, Pl. Rantu, G. Malabika, et al, Prevalence of osteoporosis and osteopenia in advanced chronic obstructive pulmonary disease patients, Lung India. 28 (3) (2011) 184–186 Bonet T. Geneva. Sepulchretumsive anatoniapructica ex CadaveribusMorbodenatis, proponensHistoa’s Observations omniumpenéhumanicorporisaffectuum, ipsarcomoueCausasrecorditasrevelans. British Thoracic Society. Guidelines for the management of the chronic obstructive pulmonary disease. Thorax 1997;52(suppl 5). Buist AS, Sexton GJ, Nagy JM, Ross BB. The effect of smoking cessation and modification on lung function. Am Rev Respir Dis. 1976; 114: 115–122. Burrows B, Knudson RJ, Cline MG, Lebowitz MD. Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis. 1977; 115: 195–205. Burrows B. Predictors of loss of lung function and mortality in obstructive lung diseases. Eur Respir Rev. 1991;1:340-5. Cosio M, Ghezzo H, Hogg JC, et al.CBO RichtlijnOsteoporoseenFractuurPreventie. Derdeherziening (2011). http://www.cbo.nl/Downloads/1318/Definitieve%20richtlijn%20osteoporose%20 28-04-201 The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med. 1978; 298:1277–1281. Definitions, epidemiology, pathophysiology, diagnosis, and staging. Am J Respir Crit Care Med. 1995;152:supply:s78-s83. Dekhuijzen PN, Aben KK, Dekker I, et al. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J RespirCrit Care Med. 1996; 154: 813–816. Dimai HP, Domej W, Leb G, Lau KH. Bone loss in patients with untreated chronic obstructive pulmonary disease is mediated by an increase in bone resorption associated with hypercapnia. J Bone Miner Res. 2001; 16(11):2132- 2141. Domingo-Salvany A, Lamarca R, Ferrer M, et al. Health-related quality of life and mortality in male patients with chronic obstructive pulmonary disease. Am J RespirCrit Care Med 2002;166:680-685. Ezzati M. Indoor air pollution and health in developing countries. Lancet. 2005;366(9480):104-6. Fletcher CM, Tinker CM, Peto R, Speizer FE. The natural history of chronic bronchitis and emphysema. Oxford, Oxford University Press, 1976. Frost ML, Blake GM, Fogelman I (2002) A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual X-ray absorptiometry in women with a history of fracture at sites other than the spine and hip. Calcif Tissue Int. 71(3):207–211. Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and meta-analysis. Thorax. 2004;59(7):574- 80. Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2007; available from www.goldcopd.com: accessed Oct 5, 2008. Gluck O, Colice G. Recognizing and treating glucocorticoid-induced osteoporosis in patients with pulmonary diseases. Chest. 2004; 125(5):1859- 1876. Gold DR, Wang X, Wipyj D, Speizer FE, Ware JH, Dockery DW. Effects of cigarette smoking on lung function in adolescent boys and girls. N Engl J Med. 1996; 335: 931–937. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005; 352(16):1685-95. Hans D, Dargent-Molina P, Schott AM, Sebert JL, Cormier C, Kotzki PO et al (1996) Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet.. 348(9026):511–514 Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. J Am Med Ass. 2004; 292(4):490-495. Incalzi RA, Caradonna P, Ranieri P, Basso S, Fuso L, Pagano F et al. Correlates of osteoporosis in chronic obstructive pulmonary disease. Respir Med. 2000; 94(11):1079-1084 Ito K, Ito M, Elliott M, Cosio MG, Caramori G, Kon O et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease: Relationship to severity. N Engl J Med. Jindal SK, Agarwal AN, Gupta D. A review of population studies from India to estimate the national burden of chronic obstructive pulmonary disease and its association with smoking. Indian J Chest Dis Allied Sci. 2001; 43(3):139-47. Jindal SK, Aggarwal AN, Chaudhry K, Chhabra SK, D&#39;Souza GA, Gupta D, et al. A multicentric study on the epidemiology of chronic obstructive pulmonary disease and its relationship with tobacco smoking and environmental tobacco smoke exposure. Indian J Chest Dis Allied Sci. 2006;48(1):23-9. Karadag F, kirdar S, Karul AB. The value of C- reactive protein as a marker of systemic inflammation in stable chronic obstructive pulmonary disease. Eur J Int Med. 2008; 19(2):104-8.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareEvaluation of Cardiovascular Autonomic Function in Prediabetics: Need of Tomorrow English149154Amit BahetiEnglish Rajesh SarodeEnglish Sunil KumarEnglish Sourya AcharyaEnglish Anil WanjariEnglish Sachin AgrawalEnglish Shilpa BawankuleEnglishIntroduction: Cardiovascular autonomic neuropathy (CAN) is a chronic complication of diabetes with life-threatening complications ranging from resting tachycardia to sudden death. Considering hyperglycaemia as the main etiopathogenic factor of CAN, its detection in the prediabetic stage will have a huge impact in delaying the development of severe forms of CAN and its complications. Objective: This study had been planned to evaluate cardiac autonomic functions in prediabetics by cardiac autonomic reflex tests. Method: This cross-sectional study was carried out in individuals with newly detected prediabetics and normoglycemic controls attending the medicine outpatient department for routine checkups. Anthropometric indices, blood pressure and serum lipids were assessed. Cardiac autonomic reflex tests were performed and individuals were divided according to Ewing’s criteria of CAN. The cardiovascular risk factors were compared to see their association with CAN. Result: In this study CAN was found in 15.2% prediabetics and 3.6% normoglycaemic age and gender-matched controls (p=EnglishAutonomic reflex test, Cardiovascular autonomic neuropathy, Prediabetes, Diabetes, Risk factors, Anthropometric indicesIntroduction Cardiac autonomic neuropathy (CAN) is a chronic complication of diabetes with significant life-threatening effects such as resting tachycardia, reduced exercise tolerance, orthostatic hypotension, silent myocardial ischemia and infarction, arrhythmias, perioperative cardiovascular instability, cardiomyopathy, sudden death.1 CAN is caused by the impairment of the autonomic nerve fibres regulating heart rate, myocardial contractility, cardiac electrophysiology, blood vessel constriction and dilatation. The exact pathogenesis of CAN is still less understood.1,2 Many of the proposed mechanisms include hyperglycemia, autoimmunity, genetics and inflammation leading to neuronal degeneration, mitochondrial dysfunction and formation of reactive oxygen species (ROS). These factors, in particular, will decline the cardiac nerve function and thus hyperglycemia, may be considered as the main pathogenic determinant in early cardiac autonomic dysfunction.1Patients with CAN become symptomatic only in the later stages of the disease, i.e. in severe CAN with no specific treatment option being available at present. The reversal of cardiovascular autonomic neuropathy is thought to be possible in the early stages of the disease with adequate glycaemic control.2 Early diagnosis is the essential step in preventing the life-threatening complications of CAN. Out of the battery of tests available for diagnosis of CAN, Cardiac autonomic reflex tests (CART) are considered to be the gold standard, they are well standardized and non-invasive.CAN was classified into early CAN defined as the presence of one abnormal CART and severe CAN as the presence of orthostatic hypotension with two or more abnormal CART.3 Many studies are investigating cardiac autonomic dysfunction in people with diabetes, showing its prevalence ranging from 50-93%.1,2 This microvascular complication in people with diabetes is significant with uncontrolled diabetics, longer duration of diabetes and other microvascular complications like diabetic nephropathy and retinopathy.4 limited studies are evaluating CAN in prediabetics, of the various studies doing so its prevalence is found to be 10-20%.5,6 The current study was conducted to evaluate prediabetics for cardiovascular autonomic neuropathy by performing CART, its association with different cardiovascular risk factors like Body mass index, Waist-hip ratio, lipid profile and systemic hypertension and finding the prevalence of CAN by using Ewing’s criteria. Methods This prospective observational cross-sectional study was carried out in the department of medicine, at rural Medical College, in rural central India, from October 2017 to September 2019, after approval by the Institutional Ethics Committee with an approval letter numbered DMIMS (DU)/IEC/2017-18/6761. Subjects coming for routine evaluation and patient’s relatives attending medicine OPD under ‘Aadhar Yojana of Maharashtra Government (provide free of cost evaluation and treatment) were screened for prediabetes. Subjects with prediabetes as per WHO criteria i.e. fasting plasma glucose (FPG) of 6.1-6.9 mmol/L (110 to 125 mg/dL) and 2 h plasma glucose of 7.8-11.0 mmol/L (140-200 mg/dL) after ingestion of 75 g of oral glucose load or a combination of the two based on a 2 h oral glucose tolerance test (OGTT) were divided into cases and age and gender-matched normoglycaemic were taken as control subjects.7 Selection of controls was taken from the subjects coming from the aadhar yojna and age and gender matching was done on a group basis. Sample size formula based on prevalence 5was used: N= Z 1-α/22*p* (1-P) /d2 We used Z 1-α/2= 1.96, P= 20%, i.e. 0.2, d = 5%, i.e. 0.05 in the equation. So by applying the above formula, N = 1.96 2*0.2*(1-0.2)/ (0.05 2) = 245.86. Thus 250 subjects were taken in both case and control groups. Both these groups were interviewed, examined, investigated in the study after informed written consent. Subjects with diabetes mellitus, acute coronary syndrome and ischemic heart disease, arrhythmias or taking anti-arrhythmic drug therapy, stroke, peripheral vascular diseases, chronic alcoholism, history of taking medications like antidepressants, beta-blockers and those who were unable to perform CARTs were excluded from the study shown in flow chart [figure 1]. All patients underwent a thorough anthropometric and physical examination, including measurement of body mass index (BMI), Waist Hip ratio, resting heart rate and blood pressure. The subjects were divided into different categories as per,(I) WHO Categories of Body Mass Index (BMI) for the Asia-Pacific Region into underweight (Englishhttp://ijcrr.com/abstract.php?article_id=4153http://ijcrr.com/article_html.php?did=41531. Fisher VL, Tahrani AA. Cardiac autonomic neuropathy in patients with diabetes mellitus: current perspectives. Diabetes Metab Syndr Obes. 2017;10:419-434. 2. Pathak A, Gupta S, Kumar S, Agrawal S. Evaluation of cardiovascular autonomic nervous functions in diabetics: Study in a rural teaching hospital. J Pract Cardiovasc Sci. 2017;3:150-7 3. Ewing DJ, Clarke BF. Diagnosis and management of diabetic autonomic neuropathy. Br Med J Clin Res Ed. 1982;285(6346):916–8. 4. Ahire C, Sarode V, Jadhav K, Shreeram V, Gaidhani N. Prevalence of cardiac autonomic neuropathy in short and long-standing type 2 diabetics in western Maharashtra. Int J Basic Appl Med Res. 2014;3:252-9. 5. Dimova R, Tankova T, Guergueltcheva V, Tournev I, Chakarova N, Grozeva G, et al. Risk factors for autonomic and somatic nerve dysfunction in different stages of glucose tolerance. J Diabetes Complications. 2017;31(3):537–43. 6. Ziegler D, Voss A, Rathmann W, Strom A, Perz S, Roden M, et al. Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey. Diabetologia. 2015;58(5):1118–28. 7. Agalya V, Sumathi S. An Assessment of Pain-Free Blood Glucose Level by Noninvasive Methods. Int J Cur Res Rev. 2021; 13 ( 05): 32-35 8. Shiwaku K, Anuurad E, Enkhmaa B, Kitajima K, Yamane Y. Appropriate BMI for Asian populations. Lancet  2004 ;363(9414):1077. 9. Vinik AI, Erbas T, Casellini CM. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. J Diabetes Investig. 2013;4(1):4–18. 10. Serhiyenko VA, Serhiyenko AA. Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment. World J Diabetes. 2018;9(1):1–24. 11. Pop-Busui R, Evans GW, Gerstein HC, Fonseca V, Fleg JL, Hoogwerf BJ, et al. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care. 2010;33(7):1578–84. 12. Witte DR, Tesfaye S, Chaturvedi N, Eaton SEM, Kempler P, Fuller JH, et al. Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus. Diabetologia. 2005;48(1):164–71.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareInfected Dentigerous Cyst - A Case Report English155158Ingle VijayaEnglish Kale LataEnglish Pawar AnujaEnglish Sarwade ChaitaliEnglishIntroduction: Most common site of dentigerous cyst is mandibular or maxillary third molar or a maxillary canine. The patient typically has no pain or discomfort, unless infected. In the present paper, we report the case of a dentigerous cyst associated with an impacted mandibular canine. This cyst was missed initially due to incomplete root canal treatment associated with the nonvital mandibular anterior tooth. The present case of a cystic lesion can create a dilemma between radicular and dentigerous cyst. Aim: we present a case of an infected dentigerous cyst associated with a non -vital mandibular anterior and over-retained primary canine. Case Report: Present case of a cystic lesion can create a dilemma between radicular and dentigerous cyst. A 23 -year old male patient reported to our dental institute with a chief complaint of pain in the lower front region of the jaw for 10 days. Discussion: In the present study, CBCT was helpful in the detection of the relation of impacted canine with the adjacent vital structure which was not appreciated by OPG. Histology showed the connective tissue with dense chronic inflammatory cell infiltrate, aspirated fluid contained red blood cells suggesting that periapical inflammation from non -vital mandibular anterior spread to dentigerous cyst and caused infected dentigerous cyst. Conclusion: One year follow-up was taken healing was seen, there was no evidence of any recurrence after 1 year. English Dentigerous cyst, Radicular cyst, Horizontally impacted canine, Non-vital mandibular anterior and over-retained primary canineIntroduction- A follicular cyst is a synonym for the dentigerous cyst. Dentigerous cysts are the second most common type of odontogenic cysts after radicular cyst and also the most common developmental cysts of jaws. The term was coined by Paget in 1853 and arises from crowns of impacted, embedded, or unerupted teeth.  [1] A dentigerous cyst is usually attached at the cementoenamel junction. Dentigerous cyst is a developmental cyst but inflammation can be one of the etiology. The most commonly involved teeth are maxillary ad mandibular molar and maxillary canine. [2] The present case of a cystic lesion can create a dilemma between radicular and dentigerous cyst. we present a case of an infected dentigerous cyst associated with a non-vital mandibular anterior tooth and over-retained primary canine. CASE REPORT- A 23 -year old male patient reported to our dental institute with a chief complaint of pain in the lower front region of the jaw for 10 days. He was apparently alright 3 months back, then he noticed swelling in gums in the lower front region of the jaw. The swelling was insidious in onset. The swelling persisted and grew progressively to present size. He experienced throbbing pain and Continuous discomfort, so he visited the department of oral medicine & radiology. Detailed history revealed the traumatic injury in the lower anterior region of jaw 13 years back in the lower front region of the jaw at age of 10yrs. The pain recurred 6 months pain for which he underwent root canal treatment with lower anterior teeth, furthered he discontinued treatment resulting incomplete root canal treatment. There was not any remarkable medical history. On clinical examination, Extraorally there was no facial asymmetry. The single right submandibular lymph node was palpable, tender and movable of size approx. 1x1 cm. No, other abnormalities were detected. On intraoral examination, Solitary diffuse swelling is seen in the lower front region of the jaw of size approx. 2x1.5 cm, smooth surface extending from mesial aspect of 31 to mesial aspect of 83 horizontally and vertically from labial vestibule to attached gingiva of 31 to 83. The overlying mucosa appears normal. Labial vestibule obliteration seen. Over retained 83seen. The swelling was tender on palpation firm to bony hard. Fluctuation felt at a single area suggestive of the perforation also labially cortical plate expansion was felt on palpation. Tenderness on vertical percussion positive with 41,42,83 with Grade I mobility.Vitality test was performed  31,32,41,42, 83 were non vital. A provisional diagnosis of Radicular Cyst with 31,41,42,83 was given. Differential diagnosis of Periapical abscess, Dentigerous cyst, Adenomatoid odontogenic tumour (AOT was given. INVESTIGATIONS The patient was advised Intraoral periapical radiograph with  Mandibular cross-sectional radiograph occlusal radiograph (FIG1), Orthopantamograph (fig2), CBCT(fig 3). Fine needle aspiration cytology revealed blood-tinged straw-coloured fluid. Radiographic finding with OPG was as follow Well defined lucent lesion is seen in the anterior region of the mandible with scalloped sclerotic borders. Cortical border touching one side root surface apically to CEJ with 43. The lesion is present from 44 crossing the midline and extending till 34. Horizontally impacted 43 present within the lesion. Over-retained 83 seen. The lesion is vertically extending from the middle 3rd of roots of teeth to the inferior border of the mandible. Thinning of cortical plates labially is evident, Eggshell crackling was felt. Pathologic fracture seen at lower border of mandible anterior region.  CBCT scan revealed lesion size 31.29x 16.80 x26.64 mm. Thinning of cortical plate labially is seen from 42 to 32. The lesion is involving the mandibular incisive nerve on the left side.Tooth 43 is displaced towards the inferior border of the mandible. The root apex of 43 is in contact with the mental canal on the right side. No evidence of root resorption with the lower anterior. Radiographic diagnosis of a dentigerous cyst with 43 was given. Differential diagnosis of Radicular cyst, Central giant cell granuloma, Adenomatoid odontogenic tumor was given. Enucleation of a dentigerous cyst along with removal of the associated permanent tooth and primary canine was done. Under general anesthesia, in supine position lesion was exposed through vestibular incision, full-thickness mucoperiosteal flap was elevated. The complete lesion was excised with resection along with buccal cortical plate (fig4 A). Impacted canine was removed [fig4 B], extraction of primary canine was performed. Haemostasis was achieved. Closure done 3-0 vicryl. On histopathological examination, the gross specimen was measuring approx. 1x 2 cm greyish coloured. H & E Stained section reveals cystic lumen lined by stratified squamous epithelium which shows arcading patterns surrounded by a fibrous capsule which is composed of bundles of collagen fibres, dense lymphocytic cell infiltration, few dilated capillaries. Also present in the stroma areas of dental follicle-like tissue. The final diagnosis is an infected dentigerous cyst with 43 was given. DISCUSSION- Dentigerous cysts are mostly involved with unerupted permanent teeth. It is usually discovered on routine radiographs but sometimes swelling may be present[3]. In this case, the patient had swelling and pain. According to Benn and Altini, a developmental dentigerous cyst might form a dental follicle and might become secondarily inflamed,  a non -vital tooth can also be a source of infection to the permanent successor. They also mentioned that the source of secondary infection can be from a radicular cyst at the apex of non-vita teeth or another source that can lead to the formation of dentigerous cyst.[4]Depending on the time of formation on dentigerous cyst around the unerupted tooth, teeth may or may not show enamel hypoplasia. Enamel hypoplasia is seen when a dentigerous cyst commences at an early stage of development of the involved tooth whereas in cases where the cyst originating after the completion of tooth development, enamel hypoplasia is not a significant factor.[5][6]In this case, cyst originated after the completion of tooth development. Basal cell nevus syndrome, mucopolysaccharidosis and cleidocranial dysplasia show bilateral and multiple cysts have been reported.[7]The most common treatment for dentigerous cyst is marsupialization, Enucleation of a dentigerous cyst along with the removal of the associated permanent tooth if it is extensively displaced, or if the lesion is extensive.[8][9]Based on radiographic appearance, dentigerous cysts are classified into three varieties, Central type, when radiolucency encircles the crown of the unerupted tooth; Lateral type, which develops laterally along with the tooth and circumferential type, where cyst completely encircles the tooth. Radiographic examination of a dentigerous cyst appears as unilocular radiolucency of varying size, with sclerotic borders associated with the crown of an unerupted tooth. If follicular space on radiography is more than 5cm, an odontogenic dentigerous cyst can be suspected. Cases of ameloblastoma, epidermoid carcinomas, squamous cell carcinoma have been reported. [10][11][12] In the present study Cone beam computed tomography is helpful in the detection of the relation of impacted canine with the adjacent vital structure which was not appreciated by Orthopantamogram. Histology showed the connective tissue with dense chronic inflammatory cell infiltrate, aspirated fluid contained red blood cells suggesting that periapical inflammation from non -vital mandibular anterior spread to dentigerous cyst and caused infected dentigerous cyst. Conclusion- Early diagnosis and treatment of dentigerous odontogenic cyst lesions are very important to prevent future complications like conversion towards malignancy and thus help to prevent morbidity. Imaging like CBCT  scan aids in diagnosis and treatment planning, knowledge of histopathologic features helps to confirm the diagnosis. One year follow up was taken healing was seen, there was no evidence of any recurrence after 1 year.(fig 5) Acknowledgement -I would like to thank Oral and maxillofacial surgeon Dr. Vijay Girhe, Oral and medicine radiologist Dr. Prachi Girhe for their contribution to the case. Conflict of interest & Source of funding -NIL CONTRIBUTION- Author 1-  has diagnosed the case, Radiographic investigations, follow-up, Manuscript preparation. AUTHOR 2-Diagnosis case, TrManuscript corrections. Author 3-  Radiographic Investigations, Photography Author 4-Follow upRadiographic Investigations Englishhttp://ijcrr.com/abstract.php?article_id=4154http://ijcrr.com/article_html.php?did=4154  Pereira T, Shetty S,  Date A. Infected Dentigerous Cyst Associated with a Horizontal Impacted Ectopic Supernumerary Tooth Induced by Trauma to the Maxillary Incisors: A Rare Case Report. J Med Sci 2018;38(3):127?130 White  SC &Pharoah MJ. Cysts.In: White  SC &Pharoah MJ editors. Oral  Radiology, Principles and Interpretation.First South Asia ed: REEELX India private limited publishers;2015.p.338. Pai N, Sheena SS, Dubey PN, Poddar P. Infected dentigerous cyst in the maxilla: report of two cases. Indian J Dent Sci 2020;12:244-7. Benn A, Altini M. Dentigerous cyst of inflammatory origin, a clinicopathologic study. Oral Surg Oral med Oral path Oral Radiol Endo.1996; 81:203-9 Patil et al. Infected Dentigerous Cyst and its Conservative Management: A Report of Two Cases. International  J Clin Paediatric dentistry. 2019 Jan-Feb; 12(1): 68–72. Browne RM, Smith AJ. Pathogenesis of odontogenic cysts. In: Investigative Pathology of the Odontogenic Cyst. CRC Press Boca Raton, 1991; p 88-109. Rajendran R. Cyst and tumours of odontogenic origin. In: Rajendran R, Sivapathasundharam B, editors. Shafer’s Textbook of Oral Pathology. 5th ed. New Delhi: Elsevier Publishers; 2006. p. 360?1. Kambalimath DH, Kambalimath HV, Agrawal SM, Singh M, Jain N, Anurag B, et al. Prevalence and distribution of odontogenic cyst in Indian population: A 10-year retrospective study. J Maxillofac Oral Surg 2014;13:10?5.  Shear M, Speight PM. Odontogenic keratocyst, in cysts of the oral and maxillofacial regions. Copenhagen: Blackwell Munksgaard. 2007. p. 59-75. Sharma et al. Inflammatory Dentigerous Cyst: A Rare Entity. J Res Adv Dent 2014; 3:2s:4-7. Waldron CA. cysts and tumours. In: Oral and Maxillofacial pathology, Neville BW, Damm DD, Allen CM, Bouquot JE, (eds), Philadelphia: W.B. Saunders, 1995, p 493- 540. Yasuoka T, Yonemoto K, Kato Y, Tatematsu N. Squamous cell carcinoma arising in a dentigerous cyst. J Oral Maxillofac Surg 2000;58:900?5.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareOral Health Status and Treatment Needs of Transgender in Pune City, Maharashtra, India: A Pilot Survey English159163Abhishek KumbhalwarEnglish Sahana - Hedge ShetiyaEnglish Pradnya KakodkarEnglish Vini MehtaEnglishEnglishTransgender, Eunuchs, Oral Health Status, HijrasIntroduction The term EUNUCH is derived from a Greek word meaning “Keeper of the bed”. 1-3 In India, eunuchs are also called ‘Hijra’, which refers to the third gender or transgender.1 Telegraphic report shows that India has an estimated 1.5 million eunuchs4 but, the census data on them does not exist, so it is impossible to make an accurate enumeration as they continue to persist as a marginalized and secretive community.1Their sources of livelihood mainly include performing at marriages and birth celebrations, badhai (ritual performing) Basti/mangti (begging) for alms, and prostitution. 3 In India, there are few studies 4,5that have been done to assess risk behaviours including the number and type of sex partners, condom use, knowledge of sexually transmitted infection, HIV/AIDS, and drug/substance use among hijras. In transgender people, a high prevalence of oral diseases is expected commonly because of the stigma associated with their gender, because of their secretive lifestyle, and their fear of approaching the doctor. Oral wellbeing has a huge impact on one&#39;s quality of life. Poor oral health, such as dental caries, periodontal disease, and tooth loss, may have a negative impact on food intake and nutritional status, putting one&#39;s health at risk.1 Similarly, systemic diseases and/or the adverse side effects of their treatments can lead to an increased risk of oral diseases. The main reason for periodontal disease is the presence of microorganisms in dental plaque which can prove to be hazardous for periodontal tissue.1 Another main aspect of oral health disease is the loss of the tooth. Lack of health education, awareness and infrastructure, poor oral hygiene practices, tobacco use, and insufficient oral healthcare facilities are the major reasons behind poor oral health leading to tooth loss. 6 One of the most common oral health diseases is dental caries. Dental caries is a preventable disease that is recognized as the primary cause of oral pain and tooth loss. This combination may accentuate the impact of oral status on well-being. It is our social responsibility to provide this segment of society with high-quality health care. 7 The data available on the oral health status of this vulnerable population is scarce. Hence the present study was being designed to assess the oral health status and treatment needs of the transgender population residing in Pune city, Maharashtra, India following the guidelines of basic oral health survey World Health Organization (WHO)1997 proforma. Materials and Methods A pilot survey was conducted to assess the oral health status and treatment needs amongst transgender residing in Pune city, Maharashtra, India.  Scientific clearance was obtained from the ethical committee and written informed content was taken before the oral examination. Based on the snowball sampling technique, 49 self-identified eunuchs residing in the city of Pune who were present at the time of examination and who fulfilled the selection criteria were examined. Transgender people who were willing to participate were included and those who belonged to the Lesbian, Gay, Bisexual and Queer communities were excluded. Information on demographic characteristics such as age, literacy level, occupation, oral health practices, and tobacco habits was collected. Clinical examination The oral health evaluation proforma of the World Health Organization (WHO)19978 was updated to collect information on oral health status and treatment needs. The principal investigator conducted the clinical examination as part of the survey. To reduce error, the investigator read, understood, and standardized his method of action. During the sample, ten subjects were examined twice, and the reproducibility for dentition status, periodontal status, and treatment need was 95%. Throughout the survey, a recording clerk was trained to assist in the recording process. The clinical examination was done in the field setting and the subjects sat comfortably. Clinical examination was done under natural light using a mouth mirror and CPI probe. Statistical Analysis The data was analyzed using Statistical Package for Social Sciences (SPSS) for Windows 26.0 (SPSS, Inc. Chicago, Illinois). Descriptive statistics were used in the form of numbers, percentages, and mean values.  Results Table 1 shows the distribution of demographic details. A total of 49 subjects were distributed into 4 age groups. The majority of the subjects (32.6) had completed secondary and higher secondary school while only 10.2% completed graduation. 69.5% of the subjects were unemployed and they earned their livelihood through begging. Table 2 is assessing oral health habits. 93.8% of the subjects used toothbrushes and toothpaste for maintaining oral hygiene. The majority of the eunuchs (57.1%) were having the habit of chewing smokeless tobacco-containing betel nut, quid, gutka, and lime whereas only 30.6% abstained from tobacco. Table 3 shows that calculus was seen in 91.83% of the eunuchs. Table 4 shows caries prevalence and treatment needs. 89.7% were having or have had caries of the permanent dentition, 87.7% were with untreated caries and 55.1% were showing four or more Decayed, Missing, and Filled Permanent Teeth. The mean number of decayed permanent teeth per person was 3.97, filled permanent teeth with decay was 0.04, missing permanent teeth due to caries was 0.59, and the mean DMFT per person was 4.89. 40 subjects required one surface filling and 16 required pulp care. Discussion It is noteworthy about the hijras that their role is so deeply rooted in Indian culture that it can accommodate a wide variety of gender identities, cross-gender behaviours, and levels of commitment without losing their cultural meaning.9 Despite having general or oral health problems, the hijras would rather bear the pain than visit a doctor owing to the stigma around them of not being treated well.9 Snowball sampling was dif?cult because standard probability sampling methods produced low response rates and responses that lack honesty. 10,11 In the present study, out of 49 subjects, 10.2% were smokers and 57.1% used smokeless. In the study done by Hongal et al.13 and Torwane et al., 1,10 54.6% of eunuchs were having the habit of chewing smokeless tobacco, 35.7% had the habit of using both smoking and smokeless tobacco. Total tobacco usage among eunuchs was found to be 90.3%. Hongal et al. 2014 13 highlighted that 24.2% were betel nut and betel quid users. However, in the study by Saravanan et al. 12 35.0% were gutkha users, 29.9% were tobacco users, 6.6 % were smokers and 5.8% were panned users. Torwane et al.10 showed that 24.2% were betel nut and betel quid users and 42.5% were tobacco users. In Chennai, Bhopal, or Pune, the usage of smokeless tobacco is in the range of 30% - 54.6 % among eunuchs. In the study by Saravanan et al. 12 47.4% was the highest per cent of the study population having calculus and Torwane et al. 10 showed 43% of the study population having calculus which is in close accordance with the current study. These findings are although most of the subjects were using toothbrushes and toothpaste. Unmet treatment needs since they do not visit the dentist regularly could be the cause of poor oral hygiene. Saravanan et al.12 showed that 69.3% had decayed teeth, 23.4% had missing teeth and 5.1% had filled teeth which is similar to our study. The reason for high caries prevalence could be due to dietary habits playing a significant role including unmet treatment needs of chronic disease. 50.4% needed extraction, 13.9% needed filling, and 5.1% needed root canal treatment in the studies done by Hongal et al. 2 and Saravanan et al. 12 which is similar to our study where the demand for treatment was high. This study should serve as the basis for a larger, nationwide survey of oral health among socially deprived communities like eunuchs. To overcome social barriers, the medical and dental practitioners combined, are needed to show responsibility and take a step forward and approach such communities. However, the results of the present study can hardly be used extensively due to the small sample size and the snowball sampling technique. Regular dental check-ups and awareness programs, as well as delivery of dental services, should be provided through the established health centres for their population. Conclusion The current findings of the study indicate that the oral health status of transgender was relatively poor with almost 91.83% of subjects having calculus. 89.7 % of subjects had caries experience, 87.7% had untreated caries and 55.1% had four or more DMFT. Lower awareness levels, pernicious tobacco habits seemed to influence the oral health status of the transgender people of Pune city, Maharashtra, India. Extensive unmet dental treatment needs, which mainly included scaling, extraction, and restoration of teeth were required. In light of the observations from the present study, transgenders should be made aware of the need and access to oral health care should be stepped up and adequate preventive measures should be taken. Conflict of Interest: None Source of Funding: None Author’s Contribution AK,SHS and PK conceived the research idea. AK collected the data and SHS supervised the findings of the work. VM performed data analysis. AK and VM drafted the article. SHS and PK critically reviewed the article. All authors discussed the results and contributed to the final manuscript. Acknowledgement We would like to thank the Transgender Guru and the eunuch’s community for their co-operation. Englishhttp://ijcrr.com/abstract.php?article_id=4155http://ijcrr.com/article_html.php?did=4155 Torwane NA, Hongal S, Saxena E, Rana PT, Jain S, Gouraha A. Assessment of periodontal status among eunuchs residing in Bhopal city, Madhya Pradesh, India: a cross-sectional study. Oral Health Dent Manag. 2014;13(3):628-33. Hongal S, Torwane N, Chandrashekhar B, Saxena V, Chavan K. An evaluation of dental prosthetic status and prosthetic needs among eunuchs (trans genders) residing in Bhopal city, Madhya Pradesh, India: a cross-sectional study. Ann Med Health Sci Res. 2014;4(6):943-8. Rehan N, Chaudhary I, Shah SK. Socio-sexual behaviour of hijras of Lahore. J Pak Med Assoc. 2009;59(6):380-4. Eunuchs of India - Deprived of Human Rights. Available from: http://www.humanrightsdefence.org/eunuchs-of-india-deprived-of-human-rights.html [cited 2021 Jan 20] Accessed from:  http://www.humanrightsdefence.org/eunuchs-of-india-deprived-of-human-rights.html Hijras/transgender women in India: HIV, human rights and social exclusion. Available from: https://www.undp.org/content/dam/india/docs/hijras_transgender_in_india_hiv_human_rights_and_social_exclusion.pdf. [cited 2020 Feb 21]  Accessed from: https://www.undp.org/content/dam/india/docs/hijras_transgender_in_india_hiv_human_rights_and_social_exclusion.pdf Ramoji Rao MV, Katari PK, Vegi L, Bypureddy TT, Prabhakara Rao KS, Tejaswi KS. Prevalence of periodontal diseases among the rural population of Mustabad, Krishna District. J Int Soc Prev Community Dent. 2016;6(Suppl 1): S59-63. Agrawal R, Gautam NR, Kumar PM, Kadhiresan R, Saxena V, Jain S. Assessment of Dental Caries and Periodontal Disease Status among Elderly Residing in Old Age Homes of Madhya Pradesh. J Int Oral Health. 2015;7(8):57-64. World Health Organization Geneva. Oral Health Survey Basic Methods 4thEdi Delhi-AITBS Publishers and Distributors; 1997;53:751-765. Nanda S, Neither Man Nor Woman: the Hijras of India. 2nd edition, Canada:Wadsworth Publishing company;1999.P-1-181. Torwane NA, Hongal S, Goel P, Chandrashekar B, Saxena V. Assessment of oral mucosal lesions among eunuchs residing in Bhopal city, Madhya Pradesh, India: a cross-sectional study. Indian J Public Health 2015;59(1):24-9. Bacchetta P. When the (Hindu) Nation Exiles its Queers. Social text Incorporated. 1999;17:141-166. Saravanan N, Reddy CVK, Veeresh DJ. A study to assess the oral health status and treatment needs of eunuchs in Chennai city.Journal of Indian Association of Public Health Dent. 2006;(8):22-30. Hongal S, Torwane NA, Goel P, Byarakele C, Mishra P, Jain S. Oral health-related knowledge, attitude and practices among eunuchs (hijras) residing in Bhopal City, Madhya Pradesh, India: A cross-sectional questionnaire survey. J Indian Soc Periodontol 2014;18(5):624-31.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareHepatic Changes Detected by Non-Invasive Biomarker, FIB4 Score and Transient Elastography in Diabetes Mellitus Patients English164172Vipin SinghEnglish Balvir SinghEnglishObjectives: To study the prevalence of hepatic changes in diabetics, evaluate possible risk factors leading to fibrosis and assess the best non-invasive test in between FIB4 score and TE to diagnose hepatic fibrosis earliest possible. Methods: The study was conducted on 304 patients, attending outdoor, diabetic clinics, patients admitted with deranged liver function test, ultrasonography finding and clinical findings inwards of post graduate department of medicine, during a period from October 2018 to November 2019. Informed consent was taken from the patients and detailed history physical examination and laboratory investigations were carried out. NAFLD was diagnosed based on TE (FibroScan). Results: Among patients screened 204 (67%) have developed hepatic involvement in the form of NAFLD picked up by TE, among this 65(32%) had fatty liver without fibrosis or mild fibrosis. The remaining 139(68%) were divided into different categories like significant fibrosis in 92 (45%), severe fibrosis in 16(8%) and cirrhosis in 31(15%)patients. The severity of NAFLD was associated with the significant increase in mean age group, mean waist-hip ratio, mean BMI, mean fasting blood sugar, mean HbA1C and mean triglyceride. Conclusion: To detect the earliest changes of NAFLD patients of diabetes mellitus should undergo liver function tests, FIB4 scoring, ultrasonography of liver and tissue elastography. Prior detection with the help of these non-invasive tests will help in the prevention of fatal complications like cirrhosis, carcinoma of the liver without the potential risk of liver biopsy in unselected patients and also help in altering the disease course.. EnglishDiabetes mellitus, FIB4 score, NAFLD, Transientelastography, Ultrasonography, Fasting blood sugarIntroduction: In India, 69.1million people are suffering from diabetes mellitus and it is estimated that India has the second-highest number of cases of diabetes mellitus in the world after China in 2015.1 In India, the prevalence of diabetes mellitus ranges from 5 to 17%. Reid et al., have shown that Indians are prone to diabetes mellitus at a much younger age with a greater risk for diabetes mellitus associated complications despite less degree of obesity.2 Almost an entire spectrum of liver diseases is noticed in patients with type 2 diabetes mellitus. This comprises abnormal liver enzymes, NAFLD, cirrhosis, hepatocellular carcinoma, and acute liver failure. The prevalence of diabetes in cirrhosis is 12.3–57%.3 Hence, patients with diabetes mellitus have a high prevalence of liver disease and patients with the liver disease having a high prevalence of diabetes mellitus. NAFLD is found to be the most common cause of chronic liver disease in USA. 2 It is described as presence of fatty liver disease in patients with 233 dB/m16; absent or mild fibrosis (F0-F1), significant liver fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4) supported TE were defined 2), 0.90 (0.86-0.93) for patients with severe fibrosis (F3), and 0.96 (0.94-0.98) or higher for patients with cirrhosis, respectively, this range was in line with the previous study of LSM using TE in NAFLD patients17. Patients with NAFLD with significant fibrosis were diagnosed with NASH. Fibroscan: Castera transient elastography kPa was 9.4 F4 cirrhosis. FIB4 score: Stages of fibrosis were defined as FIB4 score >3.25 or TE value >9.4 kPa for advanced fibrosis and a FIB4 score 9.4 kpa) had mean BMI 31.94 (Figure 6). Out of 139 patients, 92 patients (66.1%) of the fibrosis group (TE 7.5-8.5 kpa) showed mean fasting sugar level of 135.88, 16 patients (11.5%) of severe fibrosis (8.6-9.3 kpa) showed mean fasting sugar level 157.13 and rest 31 patients (22.3%) of cirrhosis group (TE>9.4 kpa) showed mean fasting sugar 173.13 (Figure 7). Out of 139 patients, 92 patients (66.1%) of the fibrosis group (TE 7.5-8.5 kpa) had mean HbA1cof 7.36, 16 patients (11.5%) of severe fibrosis (8.6-9.3 kpa) had mean HbA1c of 7.45 and the rest 31 patients (22.3%) of cirrhosis group (TE>9.4 kpa) had mean HbA1c of 8.05 (Figure 8).Figure 8: Mean HbA1c of patients according to the severity of fibrosis P-value =.0001****. Out of 139 patients, 92 patients (66.1%) of the fibrosis group (TE 7.5-8.5 kpa) had a mean triglyceride level of 189.49, 16 patients (11.5%) of fibrosis (8.6-9.3 kpa) had a mean triglyceride level of 202.63 and rest 31 patients (22.3%) of cirrhosis group (TE>9.4 kpa) had mean triglyceride level of 215.42 (Figure 9). Out of 139 patients, 92 patients (66.1%) of the fibrosis group (TE 7.5-8.5 kpa) showed a mean platelet count of 136.55, 16 patients (11.5%) of severe fibrosis (8.6-9.3 kpa) showed a mean platelet count of 131.38 and rest 31 patients (22.3%) of cirrhosis group (TE>9.4 kpa) had a mean platelet count of 125.52 (Figure 10). However, no significance was noticed among these groups which might be because of the small population study. Out of 139 patients, 92 patients (66.1%) of the fibrosis group (TE 7.5-8.5 kpa) had a mean SGPT of 106.25, 16 patients (11.5%) of severe fibrosis (8.6-9.3 kpa) had a mean SGPT of 79.06 and rest 31 patients (22.3%) of cirrhosis group (TE>9.4 kpa) had mean SGPT of 90.55 (Figure 11). Out of 139 patients, 92(66.1%) with at least significant fibrosis group (TE 7.5-8.5 kpa) were having mean SGOT 63.65 and 16 (11.5%) with severe fibrosis(8.6-9.3 kpa) were having mean SGOT 50.19 and the rest 31 patients (22.3%) of cirrhosis group (TE>9.4 kpa) having mean SGOT 52.87. Out of 304 patients, 204 patients (67%) of diabetes were having CAP value >233dB/m19and were diagnosed as NAFLD, among these 204 patients, 65 patients (32%) had fatty liver without fibrosis or mild fibrosis (9.4 kPa) and rest 108 (53%) patients were divided into significant fibrosis 92 patients (45%) and severe fibrosis (TE 8.6 -9.3 kpa) 16 patients (8%) by transient elastography (Figure 13). A patient with NAFLD having significant fibrosis was also diagnosed with NASH20. N=304 (A). Severity of hepatic fibrosis by TE scoring in NAFLD (N= 204,67%) group of patients (B). The characteristics of subjects that were identified by FIB4 and TE differed greatly (Table 2). Discussion: Out of 304 diabetic patients who underwent TE, we have found a high prevalence of NAFLD in 204 (67%) out of which 127 (62.2%) were females and 77 (37.7%) were males. Majority of patients were in the age group of 31-45 years (53.92%) followed by 46-60 years (29.41%). The proportion of significant fibrosis, advanced fibrosis and cirrhosis was 45%, 8% and 15% respectively. Our results were comparable with the previous studies conducted by Kalra S.et al., 2014 where they found 44.1 to 72% prevalence of NAFLD patients21 and Hazlehurst et al., 2016 showed 70% prevalence of NAFLD patients22. Based on fibroScan and CAPcut-off of 222 dB/m Kwok showed 72.8%occurrence of NAFLD in diabetic patients and another group of Lee-lee lai from Malaysia based on the same parameter but a different CAP cut-off of 263 dB/m showed 72.4% occurrence of NAFLD patients23,24. The CAP cut-off we used in this study was >233 dB/m which was seen to be compatible with previously reported literature. Wong V et al.,2018 recommended that by the fibroscan, CAP can be measured simultaneously with liver stiffness and thus may be used to diagnose NAFLD by confirming the presence of steatosis and assessing its severity.25 In addition, it is important to note that among diabetic patients with BMI < 25 kg/m2, 30.39 % of patients still had NAFLD. In previous studies about NAFLD, non-obese patients usually have other components of metabolic syndrome26. The presence of diabetes itself is one of the components for metabolic syndrome and the prevalence of metabolic syndrome was high in our study population of diabetics with NAFLD. With the increasing prevalence of obesity, diabetes mellitus, and metabolic syndrome, the general population of NAFLD has become the most common cause of chronic liver disease worldwide.27 Out of 139 patients with significant fibrosis and cirrhosis, the mean age for significant fibrosis was (46.80±7.68), the mean age for severe fibrosis was (47.94±7.02) and the mean age for cirrhosis was (57.97±11.32).TE value is more in higher age group patients which signifies higher chances of cirrhosis in old age patients and thus it can be concluded that the severity of NAFLD increases with age. Several groups have published systematic reviews on risk factors like age as an independent factor in the development of advanced fibrosis in patients with NASH.28-31 This study shows as the waist-hip ratio increases the severity of NAFLD defined by TE from significant fibrosis towards cirrhosis also increases, this result was comparable with the study done by Cheng PN et al., 2016 where they have linked abnormal waist circumference to a higher prevalence of NAFLD.32 Our data reports that as mean BMI increases the severity of the disease also increases which is statistically significant with a p-value = 0.006. This finding of ours was similar to the previous study done by Yen YH et al., 2018 where they have stated BMI as an independent factor correlated with clinically relevant fibrosis in patients with metabolic risk factors linked with NAFLD.33 Increased fasting blood sugar, high HbA1C, Increase triglyceride value increases the severity of the disease from significant fibrosis towards cirrhosis. Increased fasting blood sugar levels and increased serum triglyceride for a longer duration appeared as important risk factors for the development of a NAFLD. Mohan V et al., 2009 showed an increasing prevalence of NAFLD with the increase in severity of glucose intolerance.34 Another group of Alagesan et al., 2019 also revealed that poor glycemic control has a significant correlation with the increase in liver stiffness35which was also supported by several other studies.36-39 Lavekar Anurag et al., 2015 confirms that the increased BMI, metabolic syndrome, increased fasting blood glucose and serum triglycerides are potentially strong indicators of NAFLD.40 As the severity of hepatic changes increases toward more severe disease, the platelet count decreases hence low platelet count is a risk factor for the severity of NAFLD. Lower platelet levels expect a more extreme hepatic fibrosis.  Witters et al., 2008 mentioned thrombocytopenia as a marked feature of chronic liver disease and cirrhosis.41 Jaafar et al., 2019 stated that the majority of liver function tests did not reflect severe liver status in diabetic patients, except γ-glutamyl transferase and prothrombin time-international normalized ratio (0.08 and 0.00).42 Similar observations were made by Wong V et al.,2006 where they have reported prioritizing the metabolic status of the patient over the serum transaminases when determining the severity of the liver fibrosis.43 One more study showed a high proportion of patients with severe liver fibrosis and cirrhosis had normal ALT and AST.44 Our study shows that with increased fibrosis score or liver cirrhosis in patients ALT and AST don&#39;t need to also increase. As the fibrosis increases AST and ALT may even be normal which was comparable with the previous findings. Out of 304 patients, NAFLD was present in 204 (67%) patients defined by transient elastography. But out of 304 patients, only 60 (43.1%) patients were having fatty liver disease detected by ultrasonography, which is comparable with a previous study done by Amarapurkar D et al., 2007.45 This is why transient elastography can detect earlier hepatic changes as fatty liver as compared to ultrasonography. FIB4 and TE yielded a different type of fibrosis distribution in the same diabetic population. The characteristics of subjects that were identified by FIB4 and TE differed greatly. This result indicates that these two methods are not interchangeable. In this study among three TE defined fibrosis stages, CAP value is higher as fibrosis stages become severe especially in those subjects with FIB4 Englishhttp://ijcrr.com/abstract.php?article_id=4156http://ijcrr.com/article_html.php?did=4156 Danaei G, Finucane M, Lu Y, Singh G, Cowan M, Paciorek C et al. 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Prevalence of non-alcoholic fatty liver disease in urban south Indians in relation to different grades of glucose intolerance and metabolic syndrome. Diabetes Res Clin Pract. 2009 Apr;84(1):84-91. Alagesan SK. Assessment of liver involvement in type 2 diabetes mellitus using fibroscan® and correlation with risk factors. Int J Adv Med.2019 May;6(3):594. Gupte P, Amarapurkar D, Agal S, Baijal R, Kulshrestha P, Pramanik S, et al. Non-alcoholic steatohepatitis in type 2 diabetes mellitus. J Gastroenterol Hepatol. 2004 Aug;19(8):854-8. Banerjee S, Ghosh US, Dutta S. Clinicopathological profile of hepatic involvement in type-2 diabetes mellitus and its significance. J Assoc Physicians India. 2008 Aug; 56:593-9. Duseja A, Das A, Das R, Dhiman RK, Chawla Y, Bhansali A, et al. The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the West. Dig Dis Sci. 2007 Sep;52(9):2368-74. Duseja A, Das A, Dhiman RK, Chawla YK, Das R, Bhadada S, et al. Indian patients with nonalcoholic fatty liver disease presenting with raised transaminases are different at presentation. World J Gastroenterol. 2007 Jan 28;13(4):649-50. Anurag L, Aniket S, Shalik J, Amarja L, Dhananjay R, Sachin J. Non-alcoholic fatty liver disease prevalence and associated risk factors--A study from rural sector of Maharashtra. Trop Gastroenterol. 2015 Jan-Mar;36(1):25-30. Witters P, Freson K, Verslype C, Peerlinck K, Hoylaerts M, Nevens F, et al. Review article: blood platelet number and function in chronic liver disease and cirrhosis. Aliment PharmacolTher. 2008 Jun 1;27(11):1017-29. Jaafar RF, Hajj Ali AM, Zaghal AM, Kanso M, Habib SG, Halaoui AF, et al. Fibroscan and low-density lipoprotein as determinants of severe liver fibrosis in diabetic patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2019 Dec;31(12):1540-4. Wong VW, Hui AY, Tsang SW, Chan JL, Wong GL, Chan AW, et al. Prevalence of undiagnosed diabetes and postchallengehyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. Aliment PharmacolTher. 2006 Oct 15;24(8):1215-22. Pathik P, Ravindra S, Ajay C, Prasad B, Jatin P, Prabha S. Fibroscan versus simple noninvasive screening tools in predicting fibrosis in high-risk nonalcoholic fatty liver disease patients from Western India. Ann Gastroenterol. 2015 Apr-Jun;28(2):281-6. Amarapurkar D, Kamani P, Patel N, Gupte P, Kumar P, Agal S, et al. Prevalence of non-alcoholic fatty liver disease: population-based study. Ann Hepatol. 2007 Jul-Sep;6(3):161-3. Cheng PN, Chiu HC, Chiu YC, Chen SC, Chen Y. Comparison of FIB-4 and transient elastography in evaluating liver fibrosis of chronic hepatitis C subjects in community. PLoS One. 2018;13(11): e0206947. Coppell KJ, Miller JC, Gray AR, Schultz M, Mann JI, Parnell WR. Obesity and the extent of liver damage among adult New Zealanders: findings from a national survey. Obes Sci Pract. 2015 12;1(2):67-77. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003 Aug;38(2):518-26.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11HealthcareAntimicrobial Synergism between Bacteriophage UBU-SA1 and Oxacillin against Staphylococcus aureus English173177Rattanachaikunsopon PongsakEnglish Phumkhachorn ParichatEnglishIntroduction: Bacteriophages have been proven to be effective in controlling bacteria and potential as alternatives to antibiotics. Recently, combination treatments using both bacteriophages and antibiotics have been reported to substantially improve antimicrobial activity when compared with their treatments. Objectives: To isolate a lytic bacteriophage specific to Staphylococcus aureus ATCC 25923 and determine antimicrobial activity against S. aureus ATCC 25923 of the isolated bacteriophage and oxacillin when used individually and in co-treatment. Methods: A lytic bacteriophage was isolated from a hospital wastewater sample by enrichment technique. Its host range was examined using the spot test method. The effect of oxacillin on the lytic activity of the bacteriophage was determined. Lastly, the minimal inhibitory concentrations (MICs) of the bacteriophage and oxacillin against S. aureus ATCC 25923 when used individually and in co-treatment were determined using the spot test method. The fractional inhibitory concentration index (FICI) was used to analyze the co-treatment. Results: A bacteriophage, designated bacteriophage UBU-SA1, was isolated. It was found to be highly specific to S. aureus ATCC 25923. Its lytic activity was not inhibited by oxacillin. MICs of bacteriophage UBU-SA1 and oxacillin against S. aureus ATCC 25923, when used alone, were 105 PFU/mL and 50 µg/mL, respectively. Co-treatment of bacteriophage UBU-SA1 and oxacillin substantially reduced the MICs of both agents required to inhibit the bacterial host when compared with their treatments. The FICI indicated a synergistic effect between bacteriophage UBU-SA1 and oxacillin against S. aureus ATCC 25923. Conclusion: Bacteriophage UBU-SA1, by itself or in combination with antibiotics, may be useful as a therapeutic agent in controlling S. aureus English Bacteriophage, Beta-lactam, Drug resistance, Oxacillin, Synergism, Staphylococcus aureusINTRODUCTION Staphylococcus aureus is a gram-positive, nonmotile, catalase-positive and facultatively anaerobic coccus. Characteristics that differentiate S. aureus from the other species of Staphylococcus are coagulase-positive (from all other Staphylococcus species), novobiocin sensitive (from S. saprophyticus) and mannitol fermentation positive (S. epidermidis). S. aureus is a significant human pathogen causing a wide range of diseases ranging from superficial cutaneous infections to life-threatening systemic diseases. Various human systems can be infected by S. aureus such as the respiratory system, gastrointestinal system, circulatory system, urinary system and reproductive system. S. aureus causes diseases by either production of toxin or direct invasion and destruction of tissues depending on the strains involved and infection sites.1 In general, S. aureus infections are treated by drugs in the beta-lactam class such as penicillin, ampicillin, cephalosporins or oxacillin.2 However, many drug-resistant strains of S. aureus have recently emerged thereby reducing drug efficacy. Most of them are multidrug-resistant strains such as methicillin-resistant S. aureus (MRSA) strains that known so far are resistant to nearly all beta-lactam antibiotics.3 Therefore, the emergence and spread of multidrug-resistant S. aureus have posed a serious challenge to traditional antibiotic therapy. Bacteriophages are viruses capable of infecting specific bacteria. Lytic bacteriophages can bind to the outer surface of their bacterial hosts and injects their genetic materials into the host cells. Inside the hosts, more lytic bacteriophages are produced and then burst out of the host cells resulting in bacterial death. The released bacteriophages can in turn attack new bacteria. The killing cycle can continue until all bacteria are eliminated from the ecosystem.4 Based on their ability to kill bacteria, lytic bacteriophages have recently drawn researchers’ attention to use them as alternatives to antibiotics to control bacterial infections. The approach is called bacteriophage therapy. Several lytic bacteriophages have been shown to inhibit S. aureus such as bacteriophages vB_SauS_SA2,5SAJK-IND,6P68, 3A and ROSA.7 El Haddad et al.8 reported the use of a bacteriophage cocktail containing 3 different bacteriophages including phi812, 44AHJD and phi2 to inhibit S. aureus. Treatment of S. aureus mastitis in cows by bacteriophage therapy is an example of the potential of bacteriophages as alternatives to antibiotics.9 Therapeutic bacteriophages have some advantages over antibiotics in that they have been reported to be more effective but cause fewer side effects than antibiotics.10 Recently, the combination of lytic bacteriophages and antibiotics to control bacterial infections has been introduced. This approach has been proven to interfere with bacterial evolution to both bacteriophages and antibiotics; hence, increasing the effectiveness of bacterial infection treatment. Moreover, required concentrations of both agents to kill certain bacteria can be reduced thereby causing minimal side effects. Uses of lytic bacteriophages in combination with antibiotics can inhibit several pathogenic bacteria such as Shigella dysenteriae11Pseudomonas aeruginosa12and Klebsiella pneumoniae.13 Therefore, it is of interest to study bacteriophage-antibiotic combinations to control S. aureus. In this study, a bacteriophage specific to S. aureus was isolated from a hospital wastewater sample. Its host range against various bacteria was examined. The inhibitory ability against S. aureus was also determined when it was used individually and in combination with oxacillin, a common beta-lactam antibiotic used to control S. aureus infection. MATERIALS AND METHODS Bacteriophage detection A wastewater sample collected from Sappasitthiprasong Hospital, Ubon Ratchathani Province, Thailand was used as a source of a bacteriophage specific to S. aureus ATCC 25923. Bacteriophage enrichment using S. aureus ATCC 25923 as a host and preparation of bacteriophage containing cell-free filtrate (CFF) was performed according to the methods previously described.14 The detection of bacteriophage in the prepared CFF was performed by using the spot test method. A log phase culture of S. aureus ATCC 25923 was spread with a sterile swab on a BHI agar plate. Ten μL of the prepared CFF was spotted onto the bacterial lawn. The plate was incubated at 37°C for 24 h before observing the presence of a clear zone. A clear zone at the spot area, representing the lysis of host cells, indicated the activity of bacteriophage. Plaque assay The prepared CFF giving a positive result from the bacteriophage detection The prepared CFF giving a positive result from the bacteriophage detection was subjected to plaque assay as mentioned earlier14 to confirm the presence of a bacteriophage and to determine bacteriophage titer. Bacteriophage host range The spot test method (as described above) was used to determine the bacteriophage host range by using bacterial strains listed in Table 1 as tested hosts. Effect of oxacillin on bacteriophage To test if oxacillin has an inhibitory effect on bacteriophage, oxacillin was added to the CFF containing 108 PFU/mL of bacteriophage to obtain the concentrations ranging from 200 - 12.5 µg/mL. After incubation at 37°C for 24 h, the lytic activity of the bacteriophage was examined by plaque assay as mentioned above. Minimal inhibitory concentrations of bacteriophage and oxacillin when used individually To determine the minimal inhibitory concentration (MIC) of bacteriophage against S. aureus ATCC 25923, a ten-fold dilution of CFF was performed to obtain the bacteriophage concentrations ranging from 108 to 10 PFU/mL. Each bacteriophage concentration was examined for its ability to inhibit S. aureus ATCC 25923 by the spot test as mentioned above. To determine the MIC of oxacillin against S. aureus ATCC 25923, a two-fold dilution of the antibiotic was performed to obtain the concentrations ranging from 200 - 12.5 µg/mL. Each oxacillin concentration was examined for its ability to inhibit S. aureus ATCC 25923 by the spot test as mentioned above. MICs of bacteriophage and oxacillin when used in co-treatment To study the inactivation of S. aureus ATCC 25923 by bacteriophage-oxacillin combination, the bacteriophage and oxacillin, 5 µL each, were mixed to obtain final concentrations as shown in Table 2. Three different concentration levels, MIC and 2 sub MIC, of both antimicrobial agents, were included in this experiment. For bacteriophage, 3 concentration levels including MIC, MIC/10 and MIC/100 were used whereas for oxacillin, 3 concentration levels including MIC, MIC/2 and MIC/4 were used. Each bacteriophage-oxacillin combination was examined for its ability to inhibit S. aureus ATCC 25923 by the spot test as mentioned above. The inhibitory effect of the bacteriophage-oxacillin combination was analyzed by calculating the fractional inhibitory concentration index (FICI) as follows: FICI = (MICB+O/MICB) + (MICB+O/MICO) where MICB+O = MIC of bacteriophage when the bacteriophage-oxacillin combination was used MICB+O = MIC of oxacillin when the bacteriophage-oxacillin combination was used MICB = MIC of bacteriophage alone MICO = MIC of oxacillin alone The FICI was interpreted as follows: (1) a synergistic effect when FICI ≤ 0.5; (2) an additive effect when 0.5 < FICI ≤ 1, (3) an indifferent effect when 1 < FICI ≤ 4, (4) an antagonistic effect when FICI >4. RESULTS Bacteriophage detection The CFF prepared from the hospital wastewater was found to contain a bacteriophage specific to S. aureus ATCC 25923 because it produced a clear inhibition zone on the lawn of the bacterial host (Figure 1a). When the CFF was subjected to plaque assay by using S. aureus ATCC 25923 as a host, it produced clear plaques of 0.1- 0.2 mm in diameter, indicating the presence of a lytic bacteriophage in the filtrate (Figure 1b). The bacteriophage was designated bacteriophage UBU-SA1. Bacteriophage host range The host range of bacteriophage UBU-SA1 was determined by spot test using various tested bacterial strains. The results, summarized in Table 1, showed that the bacteriophage had a highly specific host range. It was able to infect only S. aureus ATCC 25923. The other tested strains were insensitive to this bacteriophage. Effect of oxacillin on bacteriophage To use bacteriophage UBU-SA1 in combination with oxacillin, it is very important to examine if the antibiotic has an inhibitory effect on the bacteriophage. After incubating bacteriophage UBU-SA1 (108 PFU/mL) with different concentrations of oxacillin ranging from 200 - 12.5 µg/mL for 24 h, it was found that the bacteriophage titers were not different from the initial titer for every oxacillin concentration. These findings suggest that oxacillin has no detrimental effect on bacteriophage UBU-SA1 and it is safe to use both of them simultaneously to inhibit S. aureus ATCC 25923. MICs of bacteriophage and oxacillin when used individually MICs of bacteriophages and antibiotics are not fixed. They are varied depending on sensitive bacterial strains. It is important to determine MICs of bacteriophages and antibiotics whenever different sensitive strains were tested. Therefore, in this study, MICs of bacteriophage UBU-SA1 and oxacillin against S. aureus ATCC 25923 had to be determined since they have not been reported anywhere. By using the spot test, it was found that concentrations of bacteriophage UBU-SA1 producing a clear inhibition zone against S. aureus ATCC 25923 were 105 PFU/mL and above. From these results, the MIC of bacteriophage UBU-SA1 against S. aureus ATCC 25923 was 105 PFU/mL. By using the spot test, it was found that concentrations of oxacillin producing a clear inhibition zone against S. aureus ATCC 25923 were 50 µg/mL and above. From these results, the MIC of oxacillin against S. aureus ATCC 25923 was 50 µg/mL. MICs of bacteriophage and oxacillin when used in co-treatment When bacteriophage UBU-SA1 or oxacillin with concentrations less than MIC values (sub MIC values) were used together to inhibit S. aureus ATCC 25923, each of them could not inhibit the bacterial host. However, when they were used in combination, they were able to inhibit S. aureus ATCC 25923 and the lowest concentrations of bacteriophages UBU-SA1 and oxacillin that could inhibit the host were 103 PFU/mL (MICB/100) and 12.5 µg/mL (MICO/4), respectively (Table 2). To analyze the effect of bacteriophage and oxacillin combination against S. aureus ATCC 25923, FICI was calculated to be 0.26. This FICI value indicates a synergistic effect between bacteriophage UBU-SA1 and oxacillin against S. aureus ATCC 25923. DISCUSSION In general, bacteriophages are often found in places where their hosts are present. Therefore, theoretically, the best way to isolate bacteriophages is to isolate them from the same samples where their hosts exist. For example, bacteriophage PAh4 specific to a fish pathogenic Aeromonas hydrophila UR1was isolated from pond water where its specific host was found.15 However, in this study, bacteriophage UBU-SA1 and its specific host are isolated from different sources. This is not an unusual case because several bacteriophages were isolated from places outside from where their specific hosts exist. These findings emphasize that bacteriophages are widespread in environments. Examples of bacteriophages isolated from sources different from places where their hosts were found include bacteriophage ST1 (specific to Salmonella Typhimurium)16 and bacteriophage Kpn5 (specific to Klebsiella pneumoniae).17 Both bacteriophages were isolated from sewage influents whereas their specific hosts were derived from clinical samples. The narrow host range of bacteriophage UBU-SA1 should be advantageous, in principle, as a therapeutic bacteriophage resulting in less harm to normal flora than commonly used antibiotics. However, bacteriophages with a narrow host range may cause limitations in their therapeutic use. This problem can be overcome by using cocktails of several bacteriophages18 or combinations of bacteriophages and antibiotics.19 To our knowledge, no beta-lactam antibiotics have been reported to have inhibitory activity against bacteriophages. For oxacillin, its bactericidal activity results from the inhibition of cell wall synthesis and is mediated through oxacillin binding to penicillin-binding proteins (PBPs). By binding to specific PBPs located inside the bacterial cell wall, oxacillin inhibits bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. Oxacillin may interfere with an autolysin inhibitor.20 Unlike bacteria, bacteriophages have no cell wall thereby escaping from the bactericidal activity of oxacillin. Several cases of synergistic effects between bacteriophages and antibiotics against bacterial hosts have been reported. Bacteriophage EPA1 when combined with gentamicin showed profound improvement in killing effect against Pseudomonas aeruginosa PAO1.21 Antimicrobial synergy between bacteriophage T4 and cefotaxime was also observed against Escherichia coli ATCC 11303.22However, antagonistic effect between bacteriophages and antibiotics against bacterial hosts has been observed. This can be in part explained by interference of antibiotics with aspects of bacterial physiology that can be crucial to bacteriophage antibacterial activities such as by interfering with bacterial ribosome functioning.23 CONCLUSION Bacteriophage UBU-SA1 was isolated from a hospital wastewater sample. It was highly specific to S. aureus ATCC 25923. The combined treatment using bacteriophage UBU-SA1 and oxacillin profoundly improved antimicrobial activity against S. aureus ATCC 25923 when compared with their treatments. With further investigation, the bacteriophage, by itself or in combination with antibiotics, may be useful as a therapeutic agent in controlling S. aureus. ACKNOWLEDGEMENTS The authors also wish to express gratitude to the management of the Faculty of Science, Ubon Ratchathani University, Thailand for the support throughout the manuscript preparation process. The authors are also grateful to authors/editors/publishers of all those articles, journals, and books from which the literature for this article has been reviewed and discussed. Conflict of Interest: The authors declare that there are no conflicts of interest. Source of funding: None Authors’ Contribution: Phumkhachorn P: Conceived idea, conducted research, collected and analysed data and wrote manuscript; Rattanachaikunsopon P: Helped in data collection, analysis and article write-up. Englishhttp://ijcrr.com/abstract.php?article_id=4157http://ijcrr.com/article_html.php?did=4157 Oliveira D, Borges A, Simoes M. Staphylococcus aureus toxins and their molecular activity in infectious diseases. Toxins2018;10(6):252. Bartash R, Nori P. Beta-lactam combination therapy for the treatment of Staphylococcus aureus and Enterococcus species bacteremia: A summary and appraisal of the evidence. Int J Infect Dis2017;63:7-12. Turner NA, Sharma-Kuinkel BK, Maskarinec SA, Eichenberger EM, Shah PP, Carugati M, et al.Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nat Rev Microbiol2019;17(4):203-18. Phumkhachorn P, Rattanachaikunsopon P. Bacteriophages: Biology and applications. J Sci Technol UBU 2019;21(3):1-13. Wang J, Zhao F, Sun H, Wang Q, Zhang C, Liu W, et al. Isolation and characterization of the Staphylococcus aureus bacteriophage vB_SauS_SA2. AIMS Microbiol 2019;5(3):285-307. Ganaie MY, Qureshi S, Kashoo Z, Wani SA, Hussain MI, Kumar R, et al. Isolation and characterization of two lytic bacteriophages against Staphylococcus aureus from India: newer therapeutic agents against Bovine mastitis. Vet Res Commun2018;42(4):289-95. Kwan T, Liu J, DuBow M, Gros P, Pelletier J. The complete genomes and proteomes of 27 Staphylococcus aureus bacteriophages. Proc Natl Acad Sci USA2005;102(14):5174-9. El Haddad L, Roy JP, Khalil GE, St-Gelais D, Champagne CP, Labrie S, et al. Efficacy of two Staphylococcus aureus phage cocktails in cheese production. Int J Food Microbiol2016;217:7-13. Hamza A, Perveen S, Abbas Z, Rehman SU. The lytic SA phage demonstrate bactericidal activity against mastitis causing Staphylococcus areus. Open Life Sci 2016;11(1):39-45. Rattanachaikunsopon P, Phumkhachorn P: Bacteriophages: Discovery and therapeutic uses in humans and animals. Int J Cur Res Rev2010;2(11):3-8. Pornnikom P, Phumkhachorn P, Rattanachaikunsopon P. Synergistic effect of bacteriophage and ampicillin against Shigella dysenteriae. Bio Bulletin 2019;5(1):5-9. Nouraldin AAM, Baddour MM, Harfoush RAHH, Essa SAM. Bacteriophage- antibiotic synergism to control planktonic and biofilm producing clinical isolates of Pseudomonas aeruginosa. Alexandria J Med 2016;52(2):99-105. Verma V, Harjai K, Chhibber S. Structural changes induced by a lytic bacteriophage make ciprofloxacin effective against older biofilm of Klebsiella pneumoniae. Biofouling 2010;26(6):729- 37. Rattanaborvorn W, Phumkhachorn P, Rattanachaikunsopon P.Potential of bacteriophages in controlling drug resistant Shigella sonnei. Asian J Microbiol Biotechnol Environ Sci2017;19(3):526-30. Phumkhachorn P, Rattanachaikunsopon P. Use of bacteriophage to control experimental Aeromonas hydrophila infection in tilapia (Oreochromis niloticus). Pak J Biol Sci2020;23(12):1659-65. Somnate T, Phumkhachorn P, Rattanachaikunsopon P. Potential of virulent bacteriophage as a biocontrol agent against Salmonella Typhimurium in beverages. J Pure Appl Microbiol 2014;8(2):1131-9. Kumari S, Harjai K, Chhibber S. Isolation and characterization of Klebsiella pneumoniae specific bacteriophages from sewage samples. Folia Microbiol2010; 55(3): 221-227. Chan BK, Abedon ST, Loc-Carrillo C. Phage cocktails and the future of phage therapy. Future Microbiol2013;8(6):769-83. Wolska KI, Grzes K, Kurek A. Synergy between novel antimicrobials and conventional antibiotics or bacteriocins. Pol J Microbiol2012;61(2):95-104. Bush K, Bradford PA. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb Perspect Med 2016;6(8):a025247. Akturk E, Oliveira H, Santos SB, Costa S, Kuyumcu S, Melo LDR, et al. Synergistic action of phage and antibiotics: Parameters to enhance the killing efficacy against mono and dual-species biofilms. Antibiotics (Basel). 2019;8(3):103. Ryan EM, Alkawareek MY, Donnelly RF, Gilmore BF. Synergistic phage-antibiotic combinations for the control of Escherichia coli biofilms in vitro. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11Healthcare Human Palatability Study for Taste Assessment of Marketed Formulation of Second-Generation Antipsychotic Drug Asenapine Maleate: The Present Scenario and Scope of Improvement     English178182Gupta NirajEnglish Mahapatra Abikesh Prasada KumarEnglish Ekambaram Vijay KumarEnglish Padhy Saubhagya KumarEnglish Introduction: Asenapine maleate, a second-generation atypical antipsychotic drug, used for the medical management, pharmacotherapy of bipolar 1 disorder and schizophrenia had been already discussed and well-established in the scientific domain. A number of scientific research findings and post-marketing studies have claimed the efficacy of the marketed formulation SAPHRIS® (Asenapine maleate) sublingual tablet in combating schizophrenia and bipolar mania. The sublingual administration of SAPHRIS® has both positive and negative effects. Medication discontinuation is more prevalent due to bitter taste of the medication thus negatively impacting the patient acceptability and compliance to dosage regimen. Objective: In the current study, we technically evaluate the palatability and patient compliance of the marketed formulation SAPHRIS® (Asenapine maleate) sublingual tablet. We have also recommended the most relevant formulation technology that can be implemented to further enhance palatability of Asenapine maleate having an outcome similar to SAPHRIS® marketed sublingual tablet formulation. Methods: Human volunteers were used to evaluate taste perception of Asenapine maleate drug substance and its marketed formulation SAPHRIS® (Asenapine maleate) tablet by human sensory evaluation test. Bitterness scale (Score 1 to 4) was used for the evaluation of bitterness level in SAPHRIS® (Asenapine maleate) Sublingual tablet and Asenapine maleate. Results: In the present study, bitterness and patient acceptability of the marketed sublingual tablet formulation of asenapine maleate SAPHRIS® was evaluated by the human sensory evaluation test. The study results revealed that Asenapine is bitter in taste but barely acceptable however its marketed formulation SAPHRIS® is bitter in taste but acceptable. Effort was given to provide the techniques available in the research domain along with suitable hydrophilic excipients that can be used to further completely mask the bitter taste in formulation. Conclusion: In conclusion, we opined that there is a need for improvement in the taste of the currently available marketed sublingual tablet dosage form of Asenapine maleate. The study also explores the relevant techniques that can be used to increase palatability among patients. Englishhttp://ijcrr.com/abstract.php?article_id=4619http://ijcrr.com/article_html.php?did=4619

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11Life Sciences Influence of Study Habits on Scholastic Achievement of Children with Visual Impairment English183188G. MadhukarEnglish Introduction: Education not only impacts on human development and economic growth but also is a fundamental requirement of democracy. Through education, people become more responsible and informed citizens, and have a voice in politics and society, which is essential for sustaining democracy. It is essential for eradicating poverty and it allows people to be more productive playing greater roles in economic life and earning a better living. Aim: To study the influence of study habits on the scholastic achievement of children with visual impairment. Objectives: To assess the study habits and scholastic achievement of children with visual impairment. To assess scholastic achievement in relation to location, gender, management, and medium. To find out the association between study habits and scholastic achievement. Method: The study demands a survey method of descriptive research. Result: Scholastic achievement, most of the students were average. Very less students were below average. Rural students were found to be better than urban students. Girls appear to be better than boys. Government school students were found to be better than NGO school students. Telugu medium students were found to be better than English medium students. Conclusion: In the given perspective, the present study has been a rewarding experience in the field of special education with special reference to children with visual impairment. The study has clearly confirmed that the influence of study habits on scholastic achievement and good study habits lead to better achievement. Discussion: Educational goals should be based on the assessed need of students with visual impairments and goals and strategies should be set throughout the student’s life continuum. EnglishStudy Habits, Scholastic Achievement, Children with Visual Impairment, Human development.economic growth, Fundamental requirement of democracyhttp://ijcrr.com/abstract.php?article_id=4620http://ijcrr.com/article_html.php?did=4620

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11Healthcare Evaluating the Impact of a Structured Curriculum on Students’ Understanding of Bulimia Nervosa at Professional Colleges     English189192Tejas S. BhosaleEnglish Samir K. ChoudhariEnglish Mahadeo ShindeEnglish Introduction: Eating disorders are serious illnesses that create substantial disruptions in the eating practices of individuals who suffer from them. Bulimia nervosa and binge eating disorders are two of the most common types of eating disorders.1 Eating disorders are mental conditions that are characterised by aberrant eating patterns and have the potential to adversely affect a person’s physical as well as mental health. Aims: The purpose of this study is to determine whether or not structured teaching programmes are effective in increasing students’ awareness of bulimia nervosa among adolescents attending selected professional colleges in Karad City. Materials and Methods: The research was conducted using an evaluative research approach, and the sample size was set at sixty individuals who were chosen using a nonprobability convenient selection technique. The self-structured knowledge questionnaire on Bulimia Nervosa was used to acquire the necessary data for this study. The surveys are divided into two parts: the first part seeks participants’ personal information, and the second part contains 25 multiple-choice questions designed to gauge adolescents’ level of familiarity with bulimia nervosa. Result: The mean score in this study was 8.9, and the standard deviation was 3.393. Approximately 58.3% of the participants had average knowledge, 16.6% bad knowledge about the subjects, and 25% had good knowledge related bulimia nervosa in the pretest. On the other hand, the results of the posttest showed that the mean score was 16.1 and the standard deviation was 3.904. In the posttest, 76.60 percent of students shown good knowledge regarding bulimia nervosa, 23.30 percent demonstrated mediocre knowledge, and zero percent demonstrated bad knowledge regarding the subject. Conclusion: It has been determined that the teaching programme on knowledge of bulimia nervosa among students is effective, and students’ knowledge has increased from an average knowledge score to an excellent knowledge score. EnglishStructure Teaching Programme, Bulimia Nervosa, Adolescents, Mental health, Mediocre, Knowledgehttp://ijcrr.com/abstract.php?article_id=4646http://ijcrr.com/article_html.php?did=4646 1. Chavez M, Insel TR. Eating disorders: National Institute of Mental Health’s perspective. American Psychologist. 2007 Apr;62(3):159. 2. Kamat MA, Aji MA, Thomas MA, Nair MA, Timalsina MA. A study to assess the knowledge regarding anorexia nervosa among adolescence girls studying in selected Physiotherapy colleges at Belagavi, Karnataka. Hindu. 2017;29:48-33. 3. Devi LT, Stella YD. Effectiveness of planned teaching programme on knowledge regarding eating disorders among teenage girls of selected school, Indore. IJAR. 2017;3(10):202-4 4. Hockenperry W, Kline W. Nursing care of childrens.7thedition. New Delhi: Reed Elsevier India Private Limited. 2006. 864-84 5. Bulimia nervosa fact sheet”. Office on women’s health. 2015;27. 6. Pal PD, Bhowmick S, Kundu A. A Study to Assess the Knowledge and Attitude of Adolescents Regarding Eating Disorders in Kolkata. Int. J. Indian Psychol. 2018;6(2):168-177 7. Hay PJ, Claudino A. Bulimia nervosa clinical evidence. 2010;1009–3275326. 8. Patal DR, Phillips EL, Pratt HD, Eating disorder, Indian J Pediatr. 1998 Jul- Aug;65(4):87-94. 9. Kumar M. A Quasi-Experimental Study to assess the effectiveness of Structured Teaching Programme on Knowledge regarding eating disorders among adolescent girls in selected senior secondary school at Sangrur Punjab India. Int. J. Nurs. Educ. 2020;8(2):241-4. 10. Devi LT, Stella YD. Effectiveness of planned teaching programme on knowledge regarding eating disorders among teenage girls of selected school, Indore. Int. J. Appl. 2017; 3(10): 202-204 11. Sharma MP. A study to assess the effective of structured teaching program regarding Eating Disorder in teenage girls in selected School in Indore, (mp). Int j med sci diagn res [Internet]. 2019 [cited 2022 Dec 15];3(7). Available from: https://www.ijmsdr. com/index.php/ijmsdr/article/view/423

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411319EnglishN2021October11Healthcare Assessing the Impact of Anxiety, Depression, and Hypertension on Sleep Quality in Hemodialysis Patients     English193197Samir K. ChoudhariEnglish Tejas S. BhosaleEnglish Shivaji H. PawarEnglish Sangita PatilEnglish Mahadeo ShindeEnglish Introduction: It is typical for people with CKD, particularly those with end-stage renal disease (ESRD), to suffer from sleep disturbances. It has been estimated that 80% of ESRD patients who are getting dialysis complain about their sleep, with daytime sleepiness being the most commonly reported symptom of poor sleep quality. In order to lessen the risk of mortality and enhance both quality of life and sleep for CKD patients, it is essential to get an understanding of sleep disorders and the connections between those disorders and other difficulties. Aims: To evaluate quality of sleep, to evaluate their degree of depression, and the Hamilton anxiety rating scale to evaluate level of anxiety. Material and Methods: This study was a quantitative survey-based study that was conducted among CKD patients. A total of 40 patients on hemodialysis were chosen using the simple random procedure. The research was carried out in the hemodialysis unit of the Krishna hospital in Karad. Patients with chronic kidney disease were given the PSQI questionnaire to evaluate their quality of sleep, the Patient Health Questionnaire (PHQ-9) to evaluate their degree of depression, and the Hamilton anxiety rating scale to evaluate their level of anxiety. Statistics, both descriptive and inferential, were applied to the study and analysis of the data that had been obtained. Result: The findings of the study indicate that about 36 (90%) of CKD patients had poor sleep quality, and there was not a significant link between anxiety or depression and the quality of sleep at a level of p 0.05. Conclusion: The findings of this study reveal that sleep issues are widespread in patients with CKD; however, there was no significant association between the quality of sleep and anxiety, depression, hypertension, or the length of time Chronic Kidney Disease patients spent on hemodialysis. EnglishAnxiety, Depression, Hypertension, Quality of sleep, Chronic Kidney Disease patients, Inferentialhttp://ijcrr.com/abstract.php?article_id=4654http://ijcrr.com/article_html.php?did=4654 1. Retna Sahuja S. Effectiveness of aloevera juice on reduction of blood glucose level among patients with diabetes mellitus in Kulasekharam village at Kanyakumari district (Doctoral dissertation, Sri. K. Ramachandran Naidu College of Nursing, Sankarankovil). 2. Choudhari KS, Potdar N, Prabhuswami H, Kharat DH. A study to assess effectiveness of foot reflexology on anxiety of patients undergoing hemodialysis in tertiary care hospital, Karad. Asian J Pharmaceut Clin Res. 2017;10:345-8. 3. Gurcay E, Akinci A. Autoinflammatory diseases and physical therapy. J. Rheumatol. 2017;28(4):183-91.. 4. Maung SC, El Sara A, Chapman C, Cohen D, Cukor D. Sleep disorders and chronic kidney disease. World J. Nephrol. 2016 May 6;5(3):224. 5. Brito DC, Machado EL, Reis IA, Carmo LP, Cherchiglia ML. Depression and anxiety among patients undergoing dialysis and kidney transplantation: a cross-sectional study. Sao Paulo Med. J. 2019 Jul 15;137:137-47. 6. Tu CY, Chou YH, Lin YH, Huang WL. Sleep and emotional disturbance in patients with non-dialysis chronic kidney disease. J Formos Med Assoc. 2019 Jun 1;118(6):986-94. 7. Khan A, Khan AH, Adnan AS, Sulaiman SA, Mushtaq S. Prevalence and predictors of depression among hemodialysis patients: a prospective follow-up study. BMC public health. 2019 Dec;19(1):1-3. 8. Cohen SD, Cukor D, Kimmel PL. Anxiety in patients treated with hemodialysis. Clin J Am Soc Nephrol.. 2016 Dec 7;11(12):2250-5. 9. Motedayen M, Sarokhani D, Ghiasi B, Khatony A, Dehkordi AH. Prevalence of hypertension in renal diseases in Iran: Systematic review and meta-analysis. Int. J. Prev. Med. 2019;10. 10. Shinde M, Mane SP. Stressors and the coping strategies among patients undergoing hemodialysis. Int J Sci Res. 2014;3(2):266- 76. 11. Aggarwal HK, Jain D, Dabas G, Yadav RK. Prevalence of depression, anxiety and insomnia in chronic kidney disease patients and their co-relation with the demographic variables. Prilozi. 2017 Sep 1;38(2):35-44. 12. Masoumi M, Naini AE, Aghaghazvini R, Amra B, Gholamrezaei A. Sleep quality in patients on maintenance hemodialysis and peritoneal dialysis. Int. J. Prev. Med. 2013 Feb;4(2):165. 13. Indrarini A, Zahra AN, Yona S. The relationship between anemia, depression, duration of hemodialysis, and quality of sleep among end-stage renal disease patients. Enfermería Clínica. 2019 Sep 1;29:24-9.