Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15Healthcare Microsponge Mediated Targeted Drug Delivery System for the Treatment of Fungal Infection English0108Shubhrajit MantryEnglish Alim MominEnglish Siddhi PanhaleEnglish Sumit JoshiEnglish Ganesh DamaEnglish The microsponge delivery system is a profoundly cross-connected permeable, polymeric microsphere, polymeric system comprising of permeable microspheres that can capture and delivery them into the skin throughout a significant stretch of time. This system furnishes broadened discharge with diminish disturbance, better resistance, worked on warm, physical and compound steadiness. The principal objective of any prescription transport structure is to achieve needed gathering of the medicine in blood or tissue, which is therapeutically incredible and non-noxious for a somewhat long period in this review different strategy for planning of microsponge drug delivery system are considered. Different benefits are likewise given which shows the significance of this strategy for the delivery of medication over the other medication delivery system. An ever increasing number of advancements in delivery system are being coordinated to enhance the adequacy and cost viability of the treatment. Microsponge innovation offer entanglement of fixing and is accepted to contribute towards lessen incidental effects, further developed strength, expanded style, and improved plan adaptability. Furthermore various examinations have affirmed that microsponge systems are not bothering, non-mutagenic, non-allergenic and non-harmful Microsponge delivery innovation is being utilized at present in beauty care products, over the counter, healthy skin, and sunscreen and remedy items. EnglishMicrosponge, Target release, Topical formulation, Solvent diffusion method, Scanning electron microscopy, Drug delivery, Control release Introduction: A Microsponges Delivery System (MDS) is Protected, exceptionally cross-connected, permeable, polymeric microspheres, and polymeric framework comprising of permeable microspheres that can capture the wide scope of actives and afterward discharge them into the skin throughout a period and because of trigger".10-25 microns in measurement. Miniature wipe polymers have the flexibility to stack a wide scope of activities giving the advantages of improved item viability, gentleness, bearableness, and stretched outwear to a wide scope of skin treatments. A few unsurprising and solid frameworks were created for foundational drugs under the heading of transdermal conveyance framework (TDS) utilizing the skin as the entryway of the section. It has worked on the adequacy and security of many medications. Yet, TDS isn't commonsense for the conveyance of materials whose last objective is skin itself. Hence the need exists for a framework to boost the measure of time that a functioning fixing is available either on skin surface or inside the epidermis while limiting its transdermal entrance in the body.1 The microsponge innovation was created by Won in 1987, and the first licenses were appointed to Advanced Polymer Systems, Inc. This Company fostered an enormous number of varieties of the systems and those are applied to the restorative just as over-the-counter (OTC)also remedy drug items. At the current time, this intriguing innovation has been authorized to Cardinal Health, Inc., for use in effective items.2 The checking electron microscopy of the microsponge molecule uncovers its interior design as the " pack of marbles". The porosity is because of the interstitial spaces between the marbles. The interstitial pores can entangle many wide scopes of dynamic fixings like emollients, scents, fundamental oils, and sunscreens, hostile to infective and calming specialists. These captured microsponges may then be coordinated or figured into item frames, like creams, moisturizers, powders, cleansers, cases and tablets. At the point when these items are applied the ensnared material gets conveyed to the skin in a controlled time discharge design or a pre-customized way using a few distinctive triggers, scouring or squeezing the Microsponge after it has been applied to the skin, hoisting skin surface temperature presenting solvents for the captured materials like water, liquor or even sweat and controlling the pace of vanishing. Dynamic fixings entangled in the permeable polymeric design show modified conduct, concerning their delivery, which is limited and delayed.2 Potential features or characteristic of microsponge drug delivery systems: Microsponges show adequate soundness over pH going from 1 to 11 and at high temperatures (up to130°C). Microsponges show great similarity with different vehicles and ingredients. Microsponges have high entanglement productivity up to 50 to 60%. Microsponges are described by free streaming properties. The normal pore size of microsponges is little (0.25 μm) in a method for forestalling the entrance of microbes, in this way they do not need cleansing or expansion of preservatives. Microsponges are non-allergenic, non-bothering, non-mutagenic and non-toxic. Microsponges can ingest oil up to multiple times their weight without drying.3 Advantages of microsponge drug delivery system: Microcapsules can't typically control the delivery pace of the dynamic drug fixings (API). When the divider is burst the API held inside the microcapsules will be delivered. Can the MDS can do it, is the issue. Liposomes experience the ill effects of a lower payload, troublesome plan, restricted synthetic strength, and microbial precariousness. Do the MDS have a wide scope of a compound security and would they say they are not difficult to detail? MDS have solidness over a pH scope of 1-11. Stable up to temperature 130C. Payload is up to 50-60 %. Free streaming and financially savvy. Microsponges are tiny circles equipped for retaining skin discharges, thusly, decreasing slickness and sparkle from the skin Enhanced product performance.  Extended-release.  Diminish irritation and hence enhanced patient Compliance.  Improved product elegancy.  Improved oil control as it can absorb oil up to 6 times its weight without drying.  Allows for novel product forms.   Improves efficacy in treatment.   Cure or control confirm more promptly.  Further develop control of condition. Further develop bioavailability of same medications Adaptability to foster novel item shapes.  Non-aggravating, non-mutagenic, non-allergenic and non-harmful Further develops steadiness, warm, physical and synthetic security  Permits joining of immiscible items.  Improves material processing e.g. liquid can be converted to powders.4 Application of microsponge: Microsponge conveyance frameworks are utilized to upgrade the security, viability and tasteful nature of effective solution, over-the-counter and individual consideration items. Items being worked on or in the commercial center use the Topical Microsponge frameworks in three essential ways: As repositories delivering dynamic fixings throughout a lengthy timeframe, As repositories for retaining unfortunate substances, for example, overabundance skin oils, or As shut compartments holding fixings from the skin for shallow activity. Delivering of dynamic fixings from ordinary effective definitions throughout a lengthy timeframe is very troublesome. Beauty care products and skin health management arrangements are planned to work just on the external layers of the skin. The average dynamic fixing in traditional items is available in a moderately high focus and, when applied to the skin, might be quickly retained. The normal outcome is overmedication, trailed by a time of under medicine until the following application. Rashes and more genuine incidental effects can happen when the dynamic fixings quickly infiltrate underneath the skin's surface. Microsponge innovation is intended to permit a drawn out pace of arrival of the dynamic fixings, accordingly offering expected decrease in the secondary effects while keeping up with the restorative viability. Microsponges are permeable, polymeric microspheres that are utilized for the most part for effective and as of late for oral organization. Microsponges are intended to convey a drug dynamic fixing productively at the base portion and furthermore to improve steadiness, lessen incidental effects and change drug discharge. (Displayed in Table no.1) Composition of microsponge: Different polymers utilized in the manufacture of microsponges for effective application bring about the arrangement of a microsponge 'confine'. According to distributed writing, polymers investigated up to this point incorporate polymethacrylates or Eudragit© polymers (EudragitRS100, Eudragit RSPO, Eudragit S100), polylactide-co-glycolic corrosive, polylactic corrosive, polyvinyl benzene, polyhydroxy butyrate and ethyl cellulose. Eudragit RS100 is the most generally concentrated on polymer, inferable from its adaptable nature. The wide scope of Eudragit polymers, contrasting in control, dissolvability furthermore water penetrability, considers exceptionally custom-made delivery qualities in this framework, working with a wide scope of choices to accomplish the ideal presentation. Polymers having a place with polymethacrylate classification are Food and Drug Organization (FDA) supported, protected, non-harmful and monetary excipients, generally utilized in the drug business. The adaptability to join diverse polymethacrylate polymers offers superior control on drug discharge conduct, particularly because of medication methacrylate– polymer cooperation. Being an establishment material for microsponges, ethylcellulose is too utilized for designing of microsponges because of its nonirritating, nontoxic and no allergenic nature. Another polymer, polyvinyl benzene, has been accounted for in the creating of permeable microspheres by the fluid suspension polymerization method. Albeit, a few polymers have been investigated of late, yet just a couple of studies has been accounted for with biodegradable polymers. They can be potential excipients for the advancement of microsponge transporters for drug focusing on. Henceforth, there is a solid need to investigate biodegradable polymers for this conveyance framework. Adjacent to this, the decision of polymer should consider skin aggravation and dermal poisonousness potential. This being a main pressing issue in dermatological definitions, has been considered by a few gathering of analysts working in the area of microsponge based conveyance frameworks.5 Properties of the actives for the entrapment into microsponges: It ought to be either completely miscible in a monomer or equipped for being made miscible by the expansion of a modest quantity of a water-immiscible dissolvable. It ought to be water-immiscible or at most just marginally solvent. It ought to be latent to monomers and ought not to build the consistency of the combination during the plan. It ought to be steady when in touch with the polymerization impetus and under states of polymerization. The circular construction of the microsponges ought not to fall.6 Release mechanism of microsponge Microsponge can be designed to release given amount of active ingredients over tie in response to one or more following external triggers Pressure: Rubbing or strain applied can set dynamic fixing free from microsponge onto skin. Solubility: Microsponge stacked with water-solvent fixings like enemies of precipitants within the sight of water. The delivery can likewise be actuated by dissemination thinking about the segment coefficient of the fixing between the microsponge and the external framework. Temperature change: Some entangled dynamic fixing can be excessively gooey at room temperature to stream precipitously from microsponge onto the skin. Expanded in skin temperature can bring about an expanded stream rate and thus discharge. Drug discharge from the skin semisolid plan can be examined by utilizing Franz-type static dissemination cells. PH set off: Triggering the pH-based arrival of the dynamic can be accomplished by adjusting the covering on the microsponge. This has numerous applications in medication conveyance.7 Fungal infection: More often than not, the human species live in serene concurrence with the microorganisms that encompass them and just when the guard framework is harmed or the grouping of microbes comes to an especially high thickness, a disease might arise. Most contaminations pass by unnoticed yet now and then the tainting specialists do get a reaction of the body, which prompts clinically show signs and indications, a condition known as irresistible illness. Microbes, infections, parasites, growths, prions, worms, helminths have all been implicated in irresistible sicknesses, of which those brought about by normal infections are the most successive, and, until years and years prior, those by microorganisms the most dreaded. As procedures to control bacterial contaminations in patients improved, organisms turned into the most unsafe microorganisms. Yeasts and forms currently rank among the 10 most habitually disengaged microbes among patients in Intensive Care Units. Roughly 7% of all febrile scenes that happen during neutropenia can be credited certainly to intrusive contagious contaminations. Candida has turned into the fourth driving circulatory system detach in medical clinics in the USA, outperforming numerous generally infamous bacterial microbes. Since the eighties, an expanded rate of intrusive contagious contaminations in patients who are not in an end phase of their fundamental sickness was observed. \\trademark, which makes that numerous obtrusive parasitic diseases are not recognized while the patient is alive.8 Mycology: Parasites are momentous organic entities and they establish a different realm for reasons for characterization. Parasites are eukaryotes; they have a film encompassing their core, their cells are a lot bigger than microorganisms and their sub-atomic cycles intently look like those of plants and creatures. In any case, in contrast to mammalian cells, growths quite often have an unbending cell divider made out of chitin items that encompass their plasma layer (see figure no.4). A growth is a vegetative organic entity and is most certainly not a plant either on the grounds that parasites don't blend chlorophyll. It is a non-motile living thing and its fundamental primary unit comprises of either a chain of round and hollow cells (hyphae) or a unicellular structure or both. The most widely recognized species like Aspergillus and Candida are tracked down wherever on the planet. Gardens, jungle gyms, houses, lodgings, emergency clinics and surprisingly the skin and mucous layers have been recognized as wellsprings of organisms that caused hazardous diseases.9 Pathophysiology of fungal infections: A couple of the organisms pathogenic for people are adequately harmful to contaminate a sound host. Most are relatively innocuous except if they experience an immune-compromised patient, in whom a debilitated guard framework grants them to attack the body. Under typical conditions, the unblemished epithelial surfaces of the gastrointestinal lot will forbid attack by miniature living beings and the mucociliary hindrance of the respiratory parcel forestalls goal of parasitic cells and spores, while, interestingly, dead or harmed tissue might transform into a favorable place for contamination. Therefore intrusive contagious diseases must be positioned among the commonly crafty contaminations.10 Method of preparation of microsponges: The microsponge is formulated by two ways the one step process or by two step processes discussed in liquid-liquid suspension polymerization and Quasi emulsion solvent diffusion method which are based on the physiochemical properties of the drug. Liquid-liquid suspension polymerization: As a general rule, an answer is made involving monomers and dynamic fixing which are immiscible with water. This stage is then suspended with fomentation in a watery stage, ordinarily, it contains added substances, like surfactants and dispersants, to shape a suspension. When the suspension is set up with discrete beads of the ideal size, polymerization is affected by enacting the monomers either by catalysis, increment temperature or illumination. In the polymerization process in which it delivered 1000 of microsponge confines which are round in structure and interconnected with one another its appear as though a grapes bundle. On consummation of polymerization delivered strong particles were recuperated from the suspension. Particles are washed and dried for additional utilization.11 Quasi-emulsion solvent diffusion: This technique is by and large has two stages, the initial step is the arrangement of the inward stage and the second step is the development of the outer stage. This strategy is by and large utilized for the planning of oral and effective microsponges. In the internal natural stage first and the foremost polymer is disintegrated in ethyl liquor and medication is broken up in this arrangement by ultra-sonication at room temperature. The external stage comprises PVA arrangement in water. The arrangement is blended and separated for additional utilization. The inward stage is blended in the external stage drop astute with the assistance of mechanical stirrer. After the blending the semi emulsion drop was shaped which might facilitate dissipation of natural dissolvable produces the strong microsponges confine. The pre-arranged microsponge are sifted and dried in stove for 12 hr.12 Mechanism of action: For the active material to emerge from the matrix of the Microsponge particle at a pre-determined rate, a number of parameters can be modified taking into consideration the physical-chemical characteristics of the active agent and the environment. The vehicle in which the polymer resides plays an important role in the release rate of the active agents from the system. Initially, there is an equilibrium between the concentration of the active agent in the polymer and in the vehicle as the skin depletes the concentration of the active agent from the vehicle, the MDS releases more active agent in response to the demand caused by the shift in the equilibrium. A continuous and steady release of active agents onto the skin is accomplished with such a system. In addition, as opposed to conventional topical formulations, the MDS can act as a reservoir and continue to release active agents to the skin even after the vehicle has been absorbed by the skin or has dried out.13 Evaluation of microsponge: The microsponge are evaluated by the following parameters Particle size and size distribution analysis Drug content Entrapment efficiency Angle of repose Compressibility index Hausner&rsquo's ratio Determination of density: Bulk density Tapped density Production yield: Microsponge production yield was determined by formula mentioned below. Scanning electron microscopy: The surface topography and morphology of the prepared microsponge were examined with a scanning electron microscope. For this method using double adhesive tape, samples were mounted on a metal stub and coating with platinum/ palladium alloy under a vacuum was done. Particle size analysis: Microsponge particle size analysis was studied by using a particle size analyzer. Prepared microsponge are dispersed in double distilled water before running the sample in the instrument to ensure the light scattering signal was within the sensitivity range of the instrument. The analysis of the microsponge was carried out at room temperature, keeping the angle of detection at 900. Infrared spectroscopy: Infrared spectroscopy was determined by Fourier to transform Infrared Spectrophotometer with the KBr pellet method. Differential scanning calorimetry (DSC): To find the interaction between the drug and excipients thermal analysis is an important evaluation technique. The interaction can be identified by any changes in the thermogram. The thermogram of the drug was obtained using the DSC instrument. The powder sample of microsponge was kept in the aluminum pan and heated at a constant rate of 100 C/ min over a temperature range of 300 C to 3000 C under a nitrogen atmosphere of a flow rate of 20 ml/min.14 Evaluation of microsponge-loaded gel formation: The microsponge-prepared gel was evaluated by different parameters such as pH, appearance, viscosity, spreadability, drug content and drug release, in vitro antifungal activity and stability studies. Appearance: The microsponge-prepared gel bases were inspected visually for clarity, color and the presence of any particles. Microsponge-loaded carbopol gel shows transparent gel. PH: Microsponge-loaded gel formulation was dissolved in water and the pH was determined with the help of a digital PH meter. All the gels are tested for pH three times and an average of three determinations was calculated. Spreadability: The microsponge gels are kept between two horizontal glass slides of standard dimension. 100g weight was placed on the top of the two slides so that the formulation gets uniformly spread. The weight was removed and the excess formulation was scraped out. Where, m = weight kept on the upper slide l = length of glass slide t = time taken in the second Viscosity: The viscosity of the microsponge-loaded gel formulation was determined using a Brookfield viscometer with spindle no 6 at 10 rpm at 37 0 C temperature. Drug content: 1 gram of gel formulation containing drug equivalent to 10 mg of drug was extracted and the volume was made up to 50 ml with ethanol. The resulting solution was filtered. Suitable dilutions of the filtrate were prepared with filtrated phosphate buffer pH 5.5 and absorbance was measured at specific wavelength using UV spectrophotometer.15-16 In vitro release of microsponges gel: The in vitro release microsponges gel was performed using a modi?ed Franz di?usion cell with Spectra Pore dialysis membrane molecular weight cut o? with an e?ective di?usion area of 3 cm. The release medium was 100 ml acetate bu?er pH 4 containing 1% SLS. One gram gel or powder was placed on the dialysis membrane which was previously soaked overnight in the release medium. The receptor medium was stirred at 50 rpm and maintained at 34°C. Aliquots of 3 ml were withdrawn at predetermined intervals over 6 h and replaced by an equal volume of the fresh medium to maintain sink conditions. The samples were analyzed spectrophotometrically at 270 nm for content and drug ?ux through the membrane was calculated. In order to investigate the mechanism of drug release form microsponge, zero order, first order, Higuchi, and Korsmeyer-Peppas models were applied on the release pro?le of microsponges gel.17 In vitro antifungal activity: Antifungal activity was evaluated against Candida albicans utilizing disc di?usion method using 100 μL of suspension containing of yeast spread on Sabourand dextrose agar (SDA). Later the media had cooled and solidi?ed, the circles which have been impregnated with 100 mg of microsponge gel, the market item, without drug gel and gel containing unencapsulated drug were set on the agar surface. Circles impregnated in arrangements (50 mg/mL) were utilized as controls. The gave plates were then struggled for24 h at 37 °C, later which the zone of not actually settled Antifungal movement was introduced as the measurement of the hindrance zone in millimeters.18 In vivo evaluation of therapeutic efficacy: Animal: Grown-up Wistar rodents (280 ± 10 g) of either sexual orientation are getting. The creatures were housed in huge, open polyacrylic confines at a surrounding room temperature with 12-h light/12-h dull cycle. Rodents had free admittance to a water and rat pellets diet. Acute toxicity testing: The female rodents were utilized for the intense poisonousness testing. Hair present in the dorsal surface of the creature (2 X 2 cm) was eliminated by applying hair remover and cleaned with liquor. The screening is was stamped (1 X 1 cm) and 0.5 g of a microsponge improved gel was applied to the outer layer of a creature's skin during the perception time frame (14 days), signs, for example, erythematic and edema were surveyed.19 Evaluation of therapeutic efficacy: The male rodents were utilized for the test. The rodents were separated into four gatherings viz., typical benchmark (group I), Candida glabrata control (bunch II), standard treatment (bunch III) and microsponges enhanced gel treatment (bunch IV). Bunch II to IV creatures was changed with intravenous methylprednisolone (5mg/kg) for 3 days for enlistment and support of cell-interceded immune suppression (Organisms from stock disengages were put away in supplement agar at 27°C, streaked onto supplement stock, and brooded at 37°C for 24 h and included culture was utilized for additional trial). Candida glabrata culture was weakened with PBS and cleaned in the smooth muscle of rodent pennies and permitted to develop for 3 days until the development of Candida was seen on ischiocavernosus smooth muscle. The settlement development was affirmed by counting the province framing unit. The creatures which as cfu worth of more than 3 cfu/ml products are remembered for the review. The creatures were treated for the week time frame and outwardly noticed its actual changes. The swab culture was gathered on starting day, fourth and seventh day of the analysis for microscopical assessment. End of the trial the creatures were forfeited and ischiocavernosus smooth muscle was gathered from every one of the trial creatures and protected in 10% formalin.20 Discussion: Microsponges have a discrete advantage over the current ordinary effective dose structures for the treatment of dermatological sicknesses. A Microsponge Delivery System can capture the wide scope of actives and afterward discharge them onto the skin throughout a period and in light of trigger. It is exceptional innovation for the controlled arrival of effective specialists and comprises of microporous dabs stacked with dynamic specialists for effective and furthermore use for oral just as biopharmaceutical drug conveyance. It gives a wide scope of figuring benefits; Fluids can be changed into free streaming powders.MDS is initially produced for the effective conveyance of drugs like an enemy of skin break out, calming, against contagious, enemies of dandruff, against pruritic, rubefacients and so forth Plans can be created with contrary fixings with delayed security without the utilization of additives. Security of the bothering and sharpening medications can be expanded and modified delivery can control how much medication is delivered to the designated site. Henceforth, the microsponge drug conveyance framework center as a significant device for future developments in controlled drug conveyance framework. In this manner, microsponge has a great deal of imminent and is an exceptionally best-in-class field which is should have been investigated. Conclusion: The microsponge conveyance framework is an extraordinary innovation for the controlled arrival of macroporous dots, stacked with a functioning specialist, offering a likely decrease in aftereffects while keeping up with their helpful viability. The microsponge drug conveyance framework offers ensnarement of its fixings and is accepted to contribute toward decreased aftereffects, further developed security, expanded tastefulness and upgraded detailing adaptability. Furthermore, various investigations have affirmed that microsponge frameworks are non-disturbing, non-mutagenic, non-allergenic, and non-poisonous. This innovation is being utilized at present in beauty care products, over-the-counter skin care, sunscreens, and remedy items. This sort of medication conveyance innovation might prompt a superior comprehension of the recuperating of a few infections. Consequently, Microsponge-based medication conveyance innovation is probably going to turn into a significant medication conveyance lattice substance for different helpful applications later on. Acknowledgment:- The authors express their heartfelt gratitude to Sharadchandra Pawar College of Pharmacy, Dubmarwadi, Our, the college library, and all other sources for their cooperation and guidance in writing this review article. Source of funding: No Conflict of Interest: No conflict of interest exists. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced is the outcome. Authors’ Contribution: The concept and Design of the study were done by Alim Momin and Shubhrajit Mantry. Data acquisition and analysis were done by Alim Momin. Manuscript preparation and editing is done by Alim Momin. Englishhttp://ijcrr.com/abstract.php?article_id=4402http://ijcrr.com/article_html.php?did=4402 1. Badhe KP, Saudagar RB. A Review on Microsponge a Novel Drug Delivery System. Asian J Pharm Res. 2016;6(1):51. 2. Jadhav N, Patel V, Mungekar S, Bhamare G, Karpe M, Kadams V. Microsponge Delivery System: An updated review, current status and future prospects. J Sci Innov Res [Internet]. 2013;2(6):1097–110. Available from: www.jsirjournal.com 3. Charde MS, Ghanawat PB, Welankiwar AS, Kumar J, Chakole RD. Microsponge A Novel New Drug Delivery System: A Review. Int jounal Adv Pharm. 2013;2(6):63–70. 4. Ingale DJ, Aloorkar NH, KulkarnI AS, Patil RAP. Microsponges as Innovative Drug Delivery Systems. Int J Pharm Sci Nanotechnol. 2012;5(1):1597–606. 5. 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Formulation and evaluation of microsponge gel for topical delivery of an antifungal drug. Int J Appl Pharm. 2017;9(4):30–7. 13. Rawat pawan S, Dhyani A, Singh V, Juyal D. A brief review of microsponges: An update. Pharma Innov J [Internet]. 2017;6(5):134–9. Available from: www.thepharmajournal.com 14. Rajitha I. DEVELOPMENT AND EVALUATION OF MICROSPONGE DRUG. Int J phamacy. 2017;7(3):125–31. 15. Li Y, Gao Y, Niu X, Wu Y, Du Y, Yang Y, et al. A 5-Year Review of Invasive Fungal Infection at an Academic Medical Center. Front Cell Infect Microbiol. 2020;10(October):1–10. 16. Kumar JR, Muralidharan S, Parasuraman S. Evaluation of antifungal activity of sustained-release microsponge enriched fluconazole gel for penile candidiasis in male rats. Int J PharmTech Res. 2014;6(6):1888–97. 17. Salah S, Awad GEA, Makhlouf AIA. Improved vaginal retention and enhanced antifungal activity of miconazole microsponges gel: Formulation development and in vivo therapeutic efficacy in rats. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15Healthcareα-Amylase Inhibitory, Immunomodulatory, Phytotoxic, Antifungal Activities and Phytochemical Screening of Medicago Denticulata English0916Imran AhmadEnglish Samina AfzalEnglish Muhammad Atif ShahzadEnglishIntroduction: Plants are an alternative source for the management of a number of human disorders because of diverse metabolites. Aims: Current study targets to probe underexplored therapeutic potentials of Medicago denticulata (M. denticulata) through phytochemical and biological assays. Methods: The dried whole plant (aerial and root parts) was extracted in succession with dichloromethane (DCM) and methanol by simple maceration process and designated with codes MDWD and MDWM respectively. Results: The phytochemical investigation uncovered the occurrence of saponins, terpenoids, tannins, phenols and flavonoids in the extracts. MDWD fraction unveiled the highest total phenolic contents 54.47 μg GAE / mg dry weight (DW), The total reducing potential 58.125 μg AAE / mg DW and total antioxidant capacity 81.71 μg AAE / mg, while MDWM fraction revealed maximum flavonoids content 16.72 μg QE / mg DW. The phytotoxicity of methanol and DCM extracts exhibited 73% and 63% growth regulation respectively at concentration of 1000 μg/mL. Extracts revealed antidiabetic activity through α-amylase inhibition. The maximum inhibition i.e. 116.91% was detected at the concentration of 1000 mg / mL by DCM extract. Conclusion: Dichloromethane and methanolic extracts of M. denticulata are well-thought-out as the potential source of antioxidants and could provide immunomodulatory, antifungal, phytotoxic and a-amylase inhibition activities. EnglishAntioxidant, Flavonoids, Immunomodulatory, Medicago, Phenols, PhytochemicalINTRODUCTION The assorted plant kingdom of the world is generally acknowledged for its medicinal significance. Potential medicinal constituents of natural plants have significantly contributed in the development of many herbal therapies used for several diseases around the world.1The herbs have been utilized by all cultures for quite a long time. Each area of the world uses herbs indigenous to that area.2 The remedies derived from plants play very important role in the traditional medicine system, like Ayurveda, Egyptian and Chinese, which represents their recurrent usage till today.3 Eastern area of Mediterranean have been recognized throughout generations with a rich record of the natural medicinal herbs.4 A striking number of new drugs had been developed from terrestrial plants being utilized as medicines in China, Egypt, India and Greece from antiquated time. There is a prediction that plants can give potential bioactive compounds for development of new ‘leads’ for example, vinblastine and vincristine used in therapy of cancer.5,6 Regardless of much advancement made in synthetic drug research, natural plants and their products are yet considered as significant sources of the medicaments and have wide use in pharma industry.7, 8 From last few years, there has been increasing curiosity around world to investigate novel and hidden potentials of the traditional herbal preparations.9 Recent research in the drug discovery from medicinal plants includes multidimensional approach through combination of biological, phytochemical, botanical, and other molecular procedures. The medicinal plants drug discovery keeps on giving new significant leads against different pharmacological targets.10 Pakistan has been blessed through botanical wealth with diverse flora. Generally in deserts, western and northern seashore and mountain areas of Pakistan approximately 6000 taxa comprising the flowering plants were accounted.11 To best of our knowledge, the most of traditional plants in the vicinity have not been characterized up till now to demonstrate their biological and phytochemical potentials. Thus, current study has been concentrated predominantly on phytochemical and pharmacological profiling of M. denticulata. Genus Medicago The genus Medicago L. belonging to family Fabaceae (subfamily Papilionoideae, tribe Trifolieae) comprises of fifty species, of which Medicago sativa L. (alfalfa) is renowned. These species are perennial or annual herbs and rarely shrubs.12 Medicago polymorpha (Burr medic) is a common, polymorphic annual legume of Mediterranean origin. It has important value in many dry land farming systems as a self-reseeding and very effective nitrogen fixer.13 Fresh leaves of Medicago polymorpha cooked in water are taken orally to treat indigestion and constipation.14 MATERIALS AND METHODS Plant Collection Plant was gathered from periphery of Bahauddin Zakariya University Multan, Pakistan, during months of March and April. The plant was identified as Medicago denticulata(synonyms were Medicagopolymorpha and Burr Medic) by Dr. Zafar Ullah Zafar, The institute of pure and applied biology, Bahauddin Zakariya University Multan, Pakistan. The voucher no. R.R.Stewart.F.W.Pak.413 was provided to that plant. Extraction of plant material For effective extraction, the whole plant material was dried at a room temperature for a period of 3 to 4 weeks before it was comminuted to coarse powder and weighed. Extraction of that powdered material was done through simple maceration procedure. Weighed quantity of that powdered plant was soaked in a measured volume of the dichloromethane (DCM) solvent for 24 hours in an extraction bottle before filtration was carried out. Above process was repeated 3 times with dichloromethane solvent. Then extraction of this marc was completed in a similar way by using methanol solvent. To attain crude extract, Dichloromethane and methanol extracts were subjected to dryness in a rotary evaporator (Buchi, Switzerland) under the reduced pressure. The dichloromethane (12 g) and methanol (23.6 g) extracts collected in the separate sample bottles were labeled with codes as MDWD and MDWM respectively. Qualitative Phytochemical Analysis Preliminary phytochemical examination for extracts was completed as described by.15 Quantitative Phytochemical Analysis Total phenolic along with flavonoid contents were measured by following described procedures. Estimation of total phenolics Total phenolic contents (TPC) of M. denticulata fractions were determined using a method based on the study of 16 with a slight change. Briefly, 20 µL of the each fraction was put in the 96-well plate, followed through adding 90 µL of diluted FolinCiocalteu reagent in the each well plate. After incubating that mixture for five minutes at a room temperature 6% sodium carbonate solution (90 µL) was added and then incubated again for 1 hour at a room temperature. The absorbance was documented on microplate reader at 630 nm wavelength. Value of total phenolic content was determined as gallic acid equivalent (GAE).17 Estimation of total flavonoids Aluminum chloride based colorimetric technique was utilized for quantification of total flavonoid content (TFC), using quercetin as a standard.18 Concisely, the reaction mixture comprising 20 µL of the sample solution (20 mg/mL DMSO), 10% aluminum chloride (10 µL), 1M potassium acetate (10 µL), and 160 µL of distilled water was incubated for half an hour at room temperature. Then, spectrophotometric absorbance of this mixture was determined at 415 nm wavelength and total phenolic content was communicated µg QE/mg DW.3 Total Antioxidant Capacity (Phosphomolybdate Assay) For determination of antioxidant capacity of samples Phosphomolybdate technique was utilized.19 The assay mixture (1000 microliter) containing sodium phosphate (0.028 M), H2SO4 (0.6 M) and 0.004 M ammonium molybdate was transferred to the sample tubes holding 100 µL test sample. The mixture samples were cooled after heating for 1.5 hours at 95 ?C hot water bath. The absorbance of reaction mixture was recorded at 765 nm. As reference standard ascorbic acid was utilized.20 Total Reducing Power (Potassium Ferricyanide Colorimetric Assay) Reducing powers of the extracts were evaluated as per process described previously by.21, 22 Briefly, the mixture containing 200 µL of test extract (4 mg/mL DMSO), 0.2 mol/L phosphate buffer having pH value 6.6 (400 µL and) and 1% potassium ferricyanide [K3Fe(CN)6] were incubated at temperature 50?C for twenty minutes. About 400 µL trichloroacetic acid (10%) was added to above mixture and then centrifuged at 3000 rpm for ten minutes at a room temperature. A 500 µL solution from upper layer, distilled water (500 µL) and 100 µL FeCl3 (0.1%) were mixed. The absorbance was noted down at 700 nm wavelength and an increased value of absorbance of the mixture is related with increased reducing power. For the preparation of blank instead of the extract a 200 µL of DMSO was added to the above-mentioned reaction mixture. Reducing powers of those samples were stated as per µg ascorbic acid equivalent per mg plant dry weight (µg AAE/mg DW).23 BIOLOGICAL EVALUATION α-amylase inhibitory assay The assay was performed with the help of a modified procedure described by24 An amount 250 µL of the extract solution was placed in the tube followed by the addition of equal volume of sodium phosphate buffer (0.02M) having pH=6.9 comprising 0.5 mg/mL of ?-amylase solution. After pre-incubation of this solution at 25?C for ten minutes, an amount 250 µL of the starch solution (1%) in a sodium phosphate buffer (0.02M) with pH=6.9 was added in different intervals of time and after that incubation was done for 10 minutes at 25?C. The reaction was ended through the addition of 500 µL of dinitrosalicylic acid (DNS) reagent. Tubes were incubated in the boiling water for five minutes and then cooled at room temperature. After diluting with distilled water (5 mL), the absorbance of the reaction mixture was measured by the use of a spectrophotometer at 540 nm wavelength. By the use of the same procedure, control was set by substituting extract by distilled water. Then ?-amylase inhibitory potential was determined as %inhibition by the following given formula.25 Antifungal assay Agar tube dilution assay was performed for screening of extracts about their in vitro antifungal action against Aspergillus flavus, Candida albicans, Fusarium solani and Microsporum canis. Test samples were dissolved in dimethyl sulfoxide (DMSO) to prepare stock solution. Sabouraud dextrose agar (4%) was prepared in distilled water. After dissolving the contents with the help of a magnetic stirrer, known quantity was distributed into the screw-capped tubes. These tubes holding media were then autoclaved for 15 minutes at 121N.C. Then after cooling these tubes to 50?C, test samples were taken from the stock solution into a non-solidified Sabouraud agar medium. Then at room temperature, the tubes were permitted to solidify. Inoculation of each tube was done using a piece of the inoculum (4mm diameter) detached from 7 day old fungi growth culture. Incubation of the tubes containing culture was done for growth at an optimal temperature 28–30.C for seven days. Humidity (40-50%) in the incubator was constrained by the placement of an open pan filled with water. These cultures during incubation were observed twice in a week. The standard drugs in this assay were Miconazole and Amphotericin B. % Inhibition of fungal growth was determined by the formula given.26 Immunomodulatory assay In Luminol-enhanced chemiluminescence assay a 25 µL of diluted whole blood HBSS++ (Hanks Balanced Salt Solution, comprising magnesium chloride and calcium chloride) [Sigma, St. Louis, USA] was incubated along 25 µL extract sample that have a concentration of 50µg/mL. The control wells contain cells and HBSS++ only, no extract sample. The performance of this test was made in white half area of the 96 well plates [Costar, NY, USA], which was incubated for fifteen minutes at 37?C in the thermostat chamber of a luminometer [Labsystems, Helsinki, Finland]. After incubation, an addition of a 25 µL of serum opsonized zymosan (SOZ) [Fluka, Buchs, Switzerland] and 25 µL of intracellular reactive oxygen species (ROS) perceiving probe, luminol [Research Organics, Cleveland, OH, USA] was done in each well, with the exception of blank wells that contain HBSS++ only). The level of ROS was documented in the luminometer in terms of a relative light units (RLU).27 Phytotoxicity assay In this assay, E-Medium was prepared by mixing a number of constituents in 1L distilled water, the adjustment of pH 6-7 was done by addition of potassium hydroxide pellets (stock solution). The working E-medium was prepared via mixing 900 mL distilled water and 100 mL stock solution. 30 mg of the extract sample was dissolved into 1.5 mL of methanol to make a stock solution of sample. Extract sample was pipetted from stock solution into 3 flasks. The solvent of 3 flasks containing 10, 100 and 1000 μg/mL concentration of extract was evaporated over a night. Working E-medium (20 mL) along with plant Lemna minor (each having rosette of 2 - 3 fronds) were added to every flask (total = 20 fronds). The standard drug (paraquat) was present in other flask supplemented with E-medium. The number of fronds was note down in each flask at 7th day after keeping the flasks in the growth cabinet. The results were evaluated as percentage growth regulation by comparing with negative control.28 RESULTS Preliminary phytochemicals screening The extracts were preliminarily evaluated for presence of different phytochemical groups with the help of precise chemical-based methods. As indicated by qualitative screening, presence of the terpenoids, tannins, saponins, phenols, and flavonoids was declared in these extracts. The results indicating preliminary phytochemical screening of the extracts are presented in Table 1. Phytotoxicity bioassay The phytotoxic capability of dichloromethane and methanol extracts of the whole plant was examined with the help of Lemna minor phytotoxicity bioassay. Growth regulation (%) revealed by crude extracts is presented in Table 2. Results exposed that sample MDWM indicated % growth regulation 26% and 36% at the concentration of 10 and 100µg/mL respectively, but at a concentration of 1000µg/mL, it presented 73% growth regulation. While sample MDWD indicated % growth regulation 21% and 26% at a concentration of a 10 and 100µg/mL respectively, however at a concentration of 1000 µg/mL, it revealed 63% growth regulation. In this way, the extracts were exposed to low growth regulation at concentrations 10 and 100µg/mL, however, appeared to have moderate % growth regulation at high concentration value (1000 µg/mL) by comparing with a standard drug. Immunomodulatory activity Luminol-enhanced chemiluminescence assay showed that sample MDWD had moderate activity against ROS (reactive oxygen species) with 55.9% inhibition while sample MDWM showed insignificant immunomodulatory activity with 38.9% inhibition. The results of immunomodulatory activity are given in Table 3. Ibuprofen was used as standard for this assay with % inhibition at 25 µg/mL = 73.2% α-amylase inhibitory activity The extracts were also assessed for α-amylase inhibition activity through standard in-vitro α-amylase inhibition assay. Extracts showed highest inhibitory action against ?-amylase. The %age inhibition results of M. denticulata extracts on activity of α-amylase are given in Table 4. The %age inhibition of ?-amylase increases by increasing concentration of extract as presented in the graph (Figure 1). Antifungal activity Antifungal activity of M. denticulata extracts against 4 strains of fungi namelyAspergillus flavus, Fusarium solani, Candida albicans and Microsporum canis is mentioned in Table 5. The information obtained indicates a moderate antifungal action shown by extracts contrary to tested strains. Extracts indicated varying degree of activity against more or less all tested fungi. The maximum inhibition zone was revealed by MDWM extract against Microsporum canis. The effects were compared using standard drugs Amphotericin B and Miconazole. (Table 5) Total phenolic and flavonoid contents The recorded values of TFC and TPC in the extracts of M. denticulata are given in Table 6. The total gallic acid equivalent phenol range in the extracts was 41.357 to 54.472 μg GAE/mg DW with maximum content quantified into MDWD extract. Total flavonoid content determination presented that among the extracts, maximum amount of quercetin equivalent flavonoids 16.729 μg QE/mg DW were noted in MDWM extract followed by MDWD extract (13.493μg QE/mg DW). Total antioxidant capacity (TAC) and total reducing power (TRP) Phenolic components in several medicinal plants have been demonstrated to be promising contributor towards the antioxidant activity. It is shown that among plant extracts tested, MDWD extract was found to reveal highest antioxidant and reducing potential 81.716µg AAE /mg DW and 58.125 μg AAE/mg DW respectively. The phosphomolybdenum-based antioxidant capacity and reductive power outcomes of Medicago denticulata extracts are given in Table 6. DISCUSSION Considering the results of the qualitative screening, these plant extracts are assumed to contain some health-promoting phytochemicals like terpenoids, tannins, saponins, phenols and flavonoids. The presence of these secondary metabolites in various medicinal plants belonging to different families was also reported by.29 The past investigations confirm that Medicago genus is appreciated source of the saponins. Triterpene saponins were recognized in Medicago polymorpha as glycosides of hederagenin, echinocystic acid, bayogenin, caulophyllogenin and soyasapogenol B. The Echinocystic acid, (detected 67.3 ± 0.9% of the total sapogenins), was a main aglycone in Medicago species.30-32 A moderate immunomodulatory activity of dichloromethane extract with 55.9% inhibition was exhibited by the plant. The literature about the reported immunomodulatory activities of medicinal plants supports the current findings. Several plants native to Iran were examined for immunomodulatory properties and at higher concentrations these extracts exhibited peripheral blood lymphocytes (isolated from the healthy individual) inhibitory potential. These inhibitory properties of some plants may be due to the induction of apoptosis.33 The inhibition of ROS generation in whole blood phagocytes by herbal plants has already been reported.34 Methanolic extract of Enicostema axillare acts on cell-mediated and humoral immune functions, reducing release of inflammatory cytokines in peritoneal macrophages.35 An alcoholic extract from the bark of Mangifera indica Linn (having 2.6% mangiferin), was explored for its potential on the humoral and cell-mediated components of mice immune system. It revealed promising immunostimulatory effects.36 M. denticulata has antifungal potential like other Medicago species. The maximum inhibition zone was revealed by MDWM extract against Microsporum canis. Antifungal effect of triterpenoidal glycosides from Medicago sativa has also been previously reported.37 Among plant extracts tested, maximum phenolic contents were quantified into MDWD extract. This extract also revealed highest antioxidant and reducing potential 81.716 µg AAE /mg DW and 58.125 μg AAE/mg DW respectively. A significant correlation among reducing power, antioxidant capacity, and the total phenolic contents were shown in the investigation, signifying that the phenolic compounds may be main contributor towards antioxidant potential of that plant. Numerous classes of polyphenols, including phenolic acids, flavonoids, lignans, and stilbenes present in the medicinal plants had been linked to their antioxidant potentials which are helpful in preventing age-related diseases, mainly produced via oxidative stress.38,39 Thus, currently phenols and flavonoids assurance in these extracts propose this medicinal plant to be a source of valuable natural antioxidants. The previously reported antioxidant activity of Medicago polymorpha extract against free radicals for example DPPH, ABTS and significantly reducing power 40, 41 support the above findings. Phytotoxicity is an important factor to consider when determining a plant's allelopathic potential. The determination of a plant's phytotoxicity aids in the development of biological herbicides or naturally occuring plant growth regulators. The necessity for phytotoxic compounds cannot be overstated, as the majority of agricultural products are affected by weeds. Human health is negatively impacted by synthetic herbicides. Researchers are battling to find effective, safe and human health-friendly phytotoxic compounds. The occurrence of natural phytotoxic components in the current studied plant make it valuable to isolate important agrochemicals. Phytotoxic effects of crude methanolic extracts of various parts of some medicinal plants on the germination of radish seeds were investigated.42 The phytotoxicity of medicinal plants was also described by.43 The extracts showed a concentration-dependent significant α-amylase inhibitory activity. α-amylase catalyses hydrolysis of 1,4-glycosidic bonds of carbohydrates into monosaccharide single sugar units that can be absorbed more easily from intestine. Inhibition of α- amylase enzyme in human digestive tract is thought to be useful in treating diabetes by reducing of glucose absorption.44 It is indicated from the studies that Azadirachta indica, Mangifera indica and Murraya koenigii are beneficial to manage postprandial hyperglycemia.45 The pancreatic α-amylase inhibitory action of roselle (Hibiscus sabdariffa Linn.) tea extract was described by. 46 α-amylase enzyme was significantly inhibited by Phyllanthus amarus suggesting that the plant contains potential α-amylase inhibitor compounds that may contribute to its antidiabetic activity.47 CONCLUSION The current study concludes Medicago denticulata as a potential source of phytochemicals. The dichloromethane extract (MDWD) and methanolic extract (MDWM) have potential phenolic and flavonoid contents with important biological activities. Maximum gallic acid equivalent (GAE) total phenolic contents [54.47 and 41.35 μg GAE/mg dry weight] and quercetin equivalent (QE) total flavonoid contents (13.49 and 16.72 μg QE /mg DW) were documented in DCM and methanolic extracts of M. denticulata respectively. Maximum antioxidant capacity represented as ascorbic acid equivalent in DCM and methanol extracts was 81.71 and 72.01 01μg AAE /mg DW respectively, however reducing power noted as ascorbic acid equivalent in DCM and methanol extracts was 58.12 & 54.51 01μg AAE /mg DW. Screened plant extracts are found to have adequate antioxidant potential which may be credited to the existence of flavonoid and phenolic content. The effects of immunomodulatory activity conclude that sample MDWD revealed moderate activity against ROS. The findings also confirm the antifungal, phytotoxic and -amylase inhibitory potential of these extracts. Inhibition of enzyme α-amylase (responsible to hydrolyze carbohydrates) is a significant tactic in lowering postprandial blood glucose level. Obtained results demand further pharmacological description and the bioactivity guided isolation of those components that are responsible for these observed activities. ACKNOWLEDGEMENTS The authors would like to thank the Faculty of Pharmacy, Bahauddin Zakariya University Multan, Pakistan for the laboratory facilities to carry out this study. CONFLICT OF INTEREST The authors declare that there are no conflicts of interest. SOURCE OF FUNDING We had no funding sources for this study. Englishhttp://ijcrr.com/abstract.php?article_id=4403http://ijcrr.com/article_html.php?did=44031.      Raina H, Soni G, Jauhari N, Sharma N, Bharadvaja N. Phytochemical importance of medicinal plants as potential sources of anticancer agents. Turk J Bot. 2014;38(6):1027-35. 2.        Mirzaei-Aghsaghali A. Importance of medical herbs in animal feeding: A review. Ann. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareWhole Exome Sequencing Data Analysis for Detection of Breast Cancer Gene Variants and Pathway Study English1726Dhanyakumar GEnglish Maheswari L PatilEnglishIntroduction: Whole Exome Sequencing (WES) involves sequencing, analysis of protein-coding regions in genome. In present investigation, the potential gene variants were identified in human breast cancer genome using WES data analysis. Materials and Method: The NGS data samples with accession numbers (SRR1274896_1, SRR1274896_2) and (SRR1275000_1, SRR1275000_2) were collected from ENA database. The quality of the samples was assessed by using FastQC tool and followed by aligning samples with reference genome sequence hg38 using the Bowtie2 tool. The results were retrieved in SAM format and converted to BAM format and then to sorted bam file using SAM tools, then duplicates were removed using Picard tool. Finally, Variant Calling format file was generated using BCF tools which projected the possible gene variants in the samples. Results: The results showed variant types out of them MUC3A1 showed an average of 53 mutations, highlighting its importance as a potential gene variant observed in breast cancer. Out of nonsynonymous mutations of samples, common gene variants in samples that possess 5 and more mutations were selected. The study was carried out on pathway analysis, domain analysis, gene involvement in biological processes and gene function. Conclusion: Majority of gene variants were involved in DNA Biosynthesis and Protein Biosynthesis and also resulted in tissue-specific location. The location of these genes showed mutated genes in cytoplasm and in nucleus indicating the impact of gene variation on intracellular process. EnglishBreast cancer, Mutations, MUC3A1, Next generation Sequencing (NGS), Whole exome sequencing, MUC16INTRODUCTION Breast cancer is the most commonly occurring cancer in female.1 Breast cancer is a complex disease with a variety of risk factors. The genetic factors, environmental factors and family history helps to determine the risk of breast cancer.2The hereditary breast cancers are caused by mutations in high-penetrance genes such as BRCA1 and BRCA2, p53, PTEN, ATM, NBS1 or LKB1.2, 3 There are low-penetrance genes such as MTHFR, CYP1A1, XRCC1 and XRCC3, ERCC4/XPF which are linked in an increase or decrease of breast cancer risk.2, 4, 5PI3K is considered to be the major signaling hub downstream of HER2 receptor tyrosine kinases, this pathway is commonly mutated in breast cancer as the mutational genes in this pathway occur about more than 70% of breast cancer.6 There exists an aggressive type of breast cancer subtype called Triple-negative breast cancer (TNBC), caused by lack of estrogen receptors (ERs), progesterone receptors (PgRs), and  Erb-B2 Receptor Tyrosine Kinase 2gene.7 Due to the low incidence of this cancer type, still large scale clinical trials to be conducted in the future.8, 9 About 10% of breast cancer cases in women are linked to the hereditary due to mutations in genes.10The hereditary breast cancers are due to the mutations in BRCA1 and BRCA2.11The frequently mutated gene in breast cancer is Tp53.12Mutations in the PTEN gene is responsible for causing Cowden syndrome families also causes 25-50% lifetime breast cancer risk in women.13 Peutz-Jeghers syndrome can lead to breast cancer risk14which is caused by mutations in the LKB1 gene.15 Some of the breast cancer susceptibility genes other than BRCA1 and BRCA2 areTP53, PTEN, BARD1, BRIPI, MRE11A, NBN, RAD50, ATM, and CHEK2.16PIK3CA mutations occur during early mutational development of breast cancer and are common in ER+ (estrogen receptor) breast cancers.6 An ESR1 mutation is found in endocrine resistance in ER-positive breast cancer.17 Nowadays the cost of NGS has been reduced, the middle-class populations are able to afford NGS for preventing breast cancer.18 This investigation was focused on WES analysis of the breast cancer samples to identify the potential gene variants to predict the specific pathway, biological process and function that may be affected through the genetic mutations observed in gene variants in breast cancer conditions. MATERIALS AND METHODS Data set collection The raw exome datasets of Breast cancer tissues SRR1274896 and SRR1275000 were downloaded from ENA database. Both sample data sets of Breast Cancer were reported to be sequenced using Illumine sequencer and were paired-end type. In the present investigation, the hardware and platform used for WES pipeline include a minimum 8GB RAM with a working platform Ubuntu operating system. Quality analysis of raw data The quality analysis of downloaded raw data samples was performed using the FASTQC tool.19 FastQC generates an HTML formatted report with box plots and graph plots for mean quality scores for sequences, GC content distribution, read length distribution, sequence duplication level and detects the overrepresented sequences indicating the contamination of adapter or primer. Data Preprocessing The preprocessing was performed for low-quality bases that are expected to be present at the ends of the reads which includes removal of adapter sequences and trimming of these low-quality bases. Alignment to reference genome The next step is the alignment of datasets with the reference genome hg38 Homo sapiens downloaded from the UCSC genome web browser. The reference genome of Homo sapiens is 3.5 GB file, for this index is built using the Bowtie2 index option that generates 6 files which are used for the alignment of samples with the reference genome. Post-processing alignment The SAM format was converted to BAM (Binary Alignment Mapping) format using SAM tools call the program.20 The SAM tools sort program was used to generate the sorted BAM file followed by generating indices. Then to remove the duplicates in sequence reads Picard tool’s20Mark Duplicate program is used. Variant calling Variant calling involves identifying the genomic variants which were done in two steps using SAM tools mpileup program and BCF tools.21 SAM tool’s mpileup program computes the likelihood of aligned reads of the samples and stores the likelihoods in mpileup format. The BCF tools call command uses the genotype likelihoods generated from the previous step to call SNPs and indels, and output all identified variants in the Variant Call Format (VCF). Annotation To call the variants in data samples, SIFT (Sorting Intolerant from Tolerant) 4G annotator22was used where SIFT predicts an amino acid substitution affecting protein function. The resulting xls format file was used to find the biological process affecting from the gene also the location of gene. RESULTS Quality Analysis of Samples The raw samples downloaded from the ENA database were subjected to quality check using the FastQC tool, which generates HTML formatted report with box plots and graph plots for mean quality scores for sequences, read length and depth along with the intended coverage and overrepresented sequences. These results of quality analysis are shown in Table1 –Table4. Since there are no overrepresented sequences in the samples of breast cancer, further removal and trimming of the low-quality bases step was not performed for any samples. Alignment Summary The reads were aligned to the UCSC reference human genome hg38 using the sequence alignment tool Bowtie2. Both the samples of paired-end datasets are used for the alignment. The overall summary of alignment is listed below: SRR1274896_1.fastq -2 and SRR1274896_2.fastq 87622713 reads; of these: 87622713 (100.00%) were paired; of these: 856366 (0.98%) aligned concordantly 0 times 70510403 (80.47%) aligned concordantly exactly 1 time 16255944 (18.55%) aligned concordantly >1 times ---- 856366 pairs aligned concordantly 0 times; of these: 150735 (17.60%) aligned discordantly 1 time ---- 705631 pairs aligned 0 times concordantly or discordantly; of these: 1411262 mates make up the pairs; of these: 849837 (60.22%) aligned 0 times 254711 (18.05%) aligned exactly 1 time 306714 (21.73%) aligned >1 times 99.52% overall alignment rate The alignment summary consists of three sections; Concordant alignment:  In the above alignment result the (70510403 + 16255944) reads align concordantly which is 99.02% of reads. Discordant alignment: The remaining 856366 reads is 0.98% (100-99.02%), of these, 150735 reads align discordantly. Then, of the non-concordant fraction, 17.60% of reads (150735 reads) align discordantly. The remaining alignment whether concordant or discordant but both are aligned in paired-end mode. The rest of the reads either align as singles i.e. Read1 in one locus & Read2 in a completely different locus or one mate aligned and the other unaligned or may not align at all. Hence the reads that are in last section is Total-(concordant+ discordant).This is shown as 87622713-(86766347+150735) = 705631 reads. This alignment is in single fashion so calculate inmates (readsx2). To reach the overall alignment, count the mates in total (i.e. mates aligned in paired and mates aligned in single fashion). That would be (86766347 X 2+ 150735X2) + 254711 + 306714= 174395589mates. That is 174395589 mates aligned of total (87622713 X 2) =175245426 mates, which is 99.52%. SRR1275000_1.fastq and SRR1275000_2.fastq 85573095 reads; of these: 85573095 (100.00%) were unpaired; of these: 527907 (0.62%) aligned 0 times 65152529 (76.14%) aligned exactly 1 time 19892659 (23.25%) aligned >1 times 99.38% overall alignment rate The above alignment was obtained in unpaired format which flagged 85573095 reads. In the above alignment, (65152529 + 19892659) = 85045188 aligned reads with coverage of 99.39%. Considering the overall alignment including 85045188 reads versus 85573095 showed 99.38% coverage. Variant analysis The file from the alignment step will be in SAM format in turn stored into BAM format this is followed by the generation of sorted file and removal of duplicates is done. In variant analysis .xls file is generated from the SIFT Annotator which is used for further work. The generated .xls consists of columns chromosome name, position, reference allele, alternate allele, Transcript ID, Gene ID, Gene Name,  Region, Variant type, Reference Amino Acid, alternate  Amino Acid, Amino acid position, SIFT score, SIFT median, number of sequences, dbSNP and SIFT prediction. The variant types of genes involved in causing cancer are Non-synonymous, Non-coding, Frameshift Deletion, Frameshift Insertion, Synonymous, Substitution, Non-Frameshift Deletion, Non-Frameshift Insertion, Start Lost, Stop Loss And Stop Gain. Thesample1 (SRR1274896_1.fastq and SRR1274896_2) consists of 40,598 and sample2 (SRR1275000_1.fastq and SRR1275000_2.fastq) consists 33,307 novel genes that causes breast cancer that are resulted in the dbSNP column. There were9,985 and 9,325 non-synonymous genes observed in sampl1 and sample2 respectively that are involved in causing Breast cancer. The results of variant annotation with the non-synonymous variant type of sample1 and sample2 were tabulated; among these mutations, variant type with 5 and above were listed out. The common genes from both samples possessing 5 mutations or more were chosen and the interpretation study of all common genes is carried out using Uniprot database that describes the pathway analysis, domain analysis, gene involvement in biological process and gene function. The interpretation study of genes showed biological pathways affected from the gene variants tabulated in Table5. Further investigation is made to know the tissue-specific location of genes which is depicted in Table 6. DISCUSSION We made an attempt to analyze the gene mutation found to occur in exome of Breast cancer. Pan et al. suggested that about 50-90% of risk of breast cancer are due to the mutations with BRCA1 or BRCA2.23 Timoteo et al. reported that rare male breast cancer risk was related to the BRAC2 gene deletion was shown using Exome sequencing.24 Thompson et al. reported that exome sequencing identified the DNA repair FANCC and BLM genes which are predisposing to breast cancer.25 Johanna et al. reported FANCM gene which is susceptible for triple-negative breast cancer using WES.26 Noh et al. using exome sequencing demonstrated 7 genes with mutations XCR1, DLL1, TH, ACCS, SPPL3, CCNF and SRL may be associated in causing breast cancer.27 Sarah et al. discovered gene SF3B1 mutation as a new target for anticancer therapy using exon sequencing and the whole genome sequencing methods.28 The result of present investigation revealed that the existence of 10314 synonymous mutation in the sample1 and 9826 in sample2indicating that such mutations are coding regions that does not change the protein sequence and amino acid does not change, then the protein also remain unaffected. The existence of 9985 non-synonymous mutations in sample1 and 9325 in the sample2 indicates such mutations occur due to insertion or deletion of single nucleotide in sequence or mutation changes the single nucleotide into a codon that does not translate into the same amino acid. The existence of 6619 Frameshift deletion in sample1 and 2712 in sample2; also 7631 Frameshift insertion in sample1 and 3324 in sample2 indicates such mutations arise when the normal sequence of codons is disrupted by the insertion or deletion of one or more nucleotides, provided that the number of nucleotides added or removed is not a multiple of three and cause the reading frame to shift. The existence of 157 non-frameshift insertions in sample1 and 42 in sample2; also130 non-frameshift deletion in sample1 and 56 in sample2 indicate the mutations arises due to insertion or deletions of 3 or multiples of 3 nucleotides that do not cause frameshift changes in protein-coding sequence. The existence2890 mutation in the sample1 and 1257 number substitution mutation in sample2indicates mutations arise by substituting a single nucleotide with different nucleotide. The existence of 27 and 23 number start lost mutation in sample1 and sample2 respectively indicate, that mutations occurs when start codon prevents the original start translation site from being used. The existence of 42 stop loss mutations in sample1 and 41 in the sample2 indicates stop-loss mutation is the loss of normal stop codon by the mutation. The existence of 107 stop gain mutations in sample1 and 115 in the sample2 indicate stop gain mutation is due to the creation of stop codon. The existence of 222806 non-coding mutation in sample1 and 153407 noncoding mutations in sample 2 indicating noncoding mutation indicating nucleotide do not encode protein sequences. There were 211 and 179 genes that were non-synonymous, and showed 5 and above mutations in sample1 and sample respectively. The interpretation study was carried out on the 159 common genes among these mutations. Important genes considered through this study, AKAP13 reported to involve in G-protein coupled receptor signaling pathway, Cell Differentiation, Signal Transduction, Apoptosis playing an important role in assembling signaling complexes downstream of many different types of G protein-coupled receptors, APOL4 involved in Lipid Metabolism playing an important role in lipid exchange and transport throughout the body, GPR98, OR10G4, OR10T2, OR13C5, OR13C5, OR2T12, OR2W3, OR4L1, OR4N5, OR5H6, OR5R1 and OR6N1are reported to involve in G-protein coupled receptor signaling pathway, OBSCN is reported to involve in G-protein coupled receptor signaling pathway, Signal Transduction, Protein Biosynthesis and Apoptosis playing role in myofibrillogenesis. CDH23, COL6A3 and PKD1L1 involved in Cell Adhesion, FAT1 involved in Cell Morphogenesis, Cell Adhesion, Cell Mobility/Migration and Cell-cell signaling playing role for cellular polarization, directed cell migration and modulating cell-cell contact, FAT2 is reported to involve in Cell Adhesion, Cell Mobility/Migration playing role in the regulation of cell migration. LAMA3 involve in Cell Adhesion, Cell Differentiation, and Cell Mobility/Migration and role in mediating the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components,PCDHA9 involve in Cell Adhesion, Cell-cell signaling helps in the establishment and maintenance of specific neuronal connections in the brain, SPINK5 involve in Cell Adhesion, Cell Differentiation, and Immune Responseplays role in the  immune system by producing white blood cells called lymphocytes, CENPF is reported to involve in Cell Differentiation, Cell Division and Protein Transport, Cell Proliferation, DNA Biosynthesis, Protein Biosynthesis, Cell Cycle helps in chromosome segregation during mitosis, CEP131 involved in Cell Differentiation, Protein Transport, Cell Proliferation, Protein Biosynthesis and Cell Cycle helps in sperm flagella formation,CFAP54, MROH2B, SPATA31E1 and SYNE1 are reported to involve in Cell Differentiation, HAP1 is reported to involve in Cell Differentiation, Protein Transport, Protein Biosynthesis and Exocytosis playing role in intracellular trafficking or organelle transport. ITPKB is reported to involve in Cell Differentiation, Signal Transduction, Cell Proliferation, Protein Phosphorylation and Apoptosis helps in regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling, LAMA5 involved in Cell Differentiation, Cell Proliferation, Protein Biosynthesis, and Cell Mobility/Migration playing a role in mediating the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. GAA, MUC17 are involved in Cellular Homeostasis, CAP1 is reported to involve in Cell Morphogenesis, Signal Transduction, Endocytosis, and Cell Mobility/Migration plays part in regulating filament dynamics and has been concerned in many complex developmental and morphological processes that include mRNA localization and establishment of cell polarity.HEG1 is involved in Cell Morphogenesis. HIVEP3 is reported to involve in Cell Differentiation and Signal Transductionhelpsas a transcription factor and binds the kappaB motif in target gene and regulates nuclear factor kappaB-mediated transcription, MAP3K19 is reported to involve in Signal Transduction, Protein Phosphorylation, Apoptosis and Cell Cycle play role in regulating TGF-β-induced Smad signaling and gene expression.OR51M1, OR51Q1, OR52B6, OR52E4, OR52E6, RP1L1 and TG are reported to involve in Signal TransductionSGK223 is involved in Signal Transduction and Cell Mobility/Migration. KIF20B is reported to involve in Cell Division, Protein Transport, Cell Proliferation, Protein Biosynthesis and Cell Cycle playing role in regulating neuronal polarization.CUBN is reported to involve in Protein Transport and Endocytosis where role is the metabolism of vitamins, lipoprotein and iron by facilitating their uptake. FRAS1 and RPGR are involved in Protein Transport and Protein Biosynthesis, NACA is reported to involve in Protein Transport, Cell Proliferation, DNA Biosynthesis, Apoptosis and Protein Biosynthesis plays its role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration. CSNK2A3 is reported to involve in Cell Proliferation, MKI67 is reported to involve in Cell Proliferation and Cell Cycle helps in chromatin organization. CAND2 is involved in DNA Biosynthesis and Protein Biosynthesis playing role in the cellular repertoire of SCF (SKP1-CUL1-F-box protein) complexes, HELZ2 involved in DNA Biosynthesis and Lipid Metabolism helps in transcriptional coactivator for nuclear receptors. PPARA, PPARG, THRA, THRB and RXRA. MTRR, PARP4, ZNF208, ZNF221, ZNF534, ZNF681 and ZNF778 are reported to involve in DNA Biosynthesis, ZNF443 is reported to involve in DNA Biosynthesis and Apoptosis CHGB, HPS4, HPS4, KIAA0753, METTL22 and TTN are reported to involve in Protein Biosynthesis.PSMD13 is involved in Post Translation Modification and Protein Phosphorylation helps in maintaining protein homeostasis by removing misfolded or damaged proteins that may impair cellular functions. CRACR2A, GBP6 are reported to involve in Immune Response, CSNK2A3, MYO3A are reported to involve in Protein Phosphorylation, MYLK is involved in Protein Phosphorylation and Cell Mobility/Migration helps in regulation of epithelial cell survival. PPP1R15A is involved in Protein Phosphorylation, Apoptosis, LGALS8, SYNE2, ESPL1 and PRUNE2 are reported to involve in Cell Mobility/Migration SETX is involved in DNA Biosynthesis and Apoptosis plays role in transcription regulation by modulating RNA Polymerase II (Pol II) binding to chromatin and through interaction with proteins involved in transcription, FRAS1 is involved in Cell Communication helps in anchoring the top layer of skin by connecting the basement membrane of the top layer to the layer of skin below. MDN1, NOL9 are involved in rRNA processing. Mutations There are 5566 and 3611 genes showed less than 5 mutations in sample1 and sample2 respectively and were considered to be non-potential gene variants. 112 Genes showed 5mutations, 48 genes showed 6 mutations, 27 genes showed 7 mutations, 14 genes showed 8 mutations, 10 genes showed 9 mutations,10 genes showed 10 mutations, 3 genes showed 11 mutations,12 mutations and 13 mutations, 2 genes showed 14 mutations,15 mutations, 19 mutations, MKI67 showed 17 mutations, CENPF showed 20 mutations, MUC17showed 23 mutations, AHNAK2 showed 32 mutations, TTN showed 34 mutations, FLG showed 36 mutations, MUC16 showed 46 mutations, MUC3A showed 55 mutations in sample1. In the sample2, 88 Genes showed 5 mutations, 35 genes showed 6 mutations, 22 genes showed 7 mutations, 7 genes showed 8 mutations, 10 genes showed 9 mutations, 6 genes showed 10 mutations, 5 genes showed 11 mutations, 2 genes showed 20 mutations and 30 mutations, XIRP2 showed12 mutations AL PK2 showed 13 mutations, GPRIN2 showed 15 mutations, MKI67 showed 17 mutations, OBSCNshowed 19 mutations, TTN showed 34 mutations, MUC16 showed 45 mutations, MUC3A showed 50. The gene mutations with 5 and above were considered to be potential gene variants used for further analysis. The MUC3A showed the highest mutations in both samples making it potential gene variant observed in breast cancer conditions. Williams et.al, reported that expression of MUC3A is down-regulated in colorectal cancer.29 Rakha et al. concluded that theMUC3A expresses in human breast cancer tissues.30 Leroy et al. Park et al. Wang et al. Rakha et al. concluded that MUC3A is poor prognosis, that has been shown in pancreatic, breast, gastric, and renal cancers.30-33 The MUC16 showed 45 mutations in both samples. Das et al. stated that MUC16 plays role in tumour genesis and metastasis for ovarian cancer, pancreatic cancer and breast cancer.34Mildred et al. reported that MUC16 has C125 biomarker plays role in ovarian tumour growth and metastasis.35 Biological Pathways Affected An interpretation study was carried on common genes and study revealed the genes that affect the biological pathways and location of the mutated genes. 17 genes affected DNA biosynthesis and protein biosynthesis, 15 genes were found to be affecting cell differentiation, 14 genes were found to be affecting G-protein coupled receptor signaling pathway and signal transduction, 11 genes affected Apoptosis, 9 genes affected cell mobility/migration and cell proliferation, 8 genes affected Cell adhesion and protein transport, 7 genes were found to be affecting protein phosphorylation and cell cycle, 3 genes were found to be affecting genes cell morphogenesis, immune response and rRNA processing, 2 were found to be affecting genes were found to be affecting lipid metabolism, cellular homeostasis, cell division, post-translation modification, metabolism, cell-cell signaling and endocytosis, single gene were found to be affecting cell communication and exocytosis. In the present study, we observed the location of the 42 mutated genes product in Cytoplasm, 39 in nucleus, 36 mutated gene products were in cell membrane, 27 were in the extracellular region, 26 gene products in extracellular matrix and cytoskeleton, 7 gene products found in the mitochondrion,5 gene products found in centrosome/acrosome, 4 inlysosome, 3 in the chromosome, 2 in golgi apparatus and endosome, 1 in cell cortex. CONCLUSION Breast cancer occurs when a malignant tumor originates in the breast. As breast cancer tumors mature, they may spread to other parts of the body. In the current work WES analysis of gene variants involved in causing breast cancer were studied. The results revealed that 5,580,674 genes were found in sample1 and 3,850,125 found in sample2.  Among these genes, 9985 and 9325 genes were non-synonymous in samples 1 and sample2 respectively. 5566 genes possessed less than 5 mutations in the sample1 and 3611 showed in sample2. These genes were considered to be non-potential gene variants, hence were not used for study. 211 genes were non-synonymous with 5 and above mutations in the sample1 and 179 in sample2. Among these two samples 153 genes were common and an interpretation study was made on these common genes. The study revealed that MUC3A possessed a maximum number of mutations in both the samples (55 in sample1 and 50 in sample2) indicating potential gene variants in breast cancer condition. This MUC3A can be used as a biomarker for finding treatment for breast cancer. Also one more mucin, MUC16 showed 46 mutations in both samples.  The biological process study revealed that 17 genes affect DNA and protein biosynthesis. Also the location of these genes showed those42 mutated genes in the cytoplasm and 39 mutated genes in the nucleus indicating the impact of gene variation on the intracellular process. ACKNOWLEDGEMENTS The authors express their sincere gratitude to all the authors/ editors/publishers of those articles, journals, and books from where the literature of this article has been reviewed and discussed. Also authors especially thank Dr Sandhya Kulkarni, Principal KLE’s GH College for her invaluable support. All the authors want to thank all those who participated in this study. Conflict of Interest: All authors confirm that there are no conflicts of interest regarding this article. Source of funding:  This work does not receive any funding. Author’s Contribution: Dr. Dhanyakumar G : Clinical aspect of Brest Cancer Dr. Maheswari L Patil: Collection of Samples from databases, Whole Exome analysis of Breast cancer samples, article write-up. Englishhttp://ijcrr.com/abstract.php?article_id=4404http://ijcrr.com/article_html.php?did=4404 Parkin DM. International variation. Oncogene 2004; 23: 6329-6340. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareEffect of Apple Cider Vinegar and Cinnamon (Cinnamomum Cassia) in Combination on Lipid Profile of Mice English2732Ayesha AftabEnglish Sohail AhmadEnglish Muhammad Kashif MunirEnglish Zahid IqbalEnglish Sana RehmanEnglish Nazish MazariEnglishIntroduction: Metabolic syndrome is constituted by hyperlipidemia with presentation of diverse lipid profile including hypertriglyceridemia, hypercholesterolemia and hereditary combined hyperlipidemia. Objectives: To find the synergistic effect Cinnamomum cassia and apple cider vinegar on combined administration in albino mice. Methodology: This was an experimental study and conducted at Department of Pharmacology, Al-Nafees Medical College and Hospital Islamabad in collaboration with Animal House of the National Institute of Health, Islamabad-Pakistan. A total of 50 adult albino mice were randomly divided into 5 groups. Hyperlipidemia was induced during the first two weeks of experimentation, and this was followed by treatment period of 6 weeks. Groups were categorized as A (Normal Control), B (Treated Control), C (Treatment Group I), D (Treatment Group II), and E (Treatment Group III). Diet pattern for these groups remained to be high cholesterol, Simvastatin 0.6 mg/Kg BW, ACV upto 15% of animal feed, Cinnamon powder 6mg/Kg BW and Cinnamon with high cholesterol diet respectively. Blood samples to estimate parameters of lipid profile were collected at 0,15th, 30th, 45th and 60th days. Results: A significant decrease (pEnglishApple cider vinegar, Cinnamon, Lipid profile, Albino mice, Metabolic syndrome, LipoproteinINTRODUCTION Hyperlipidemia constitutes a metabolic syndrome with diverse lipid profile including hypertriglyceridemia, hypercholesterolemia and hereditary combined hyperlipidemia leading to various health issues like cardiovascular diseases, atherosclerosis, obesity, diabetes & insulin resistance and is major cause of deaths worldwide.1 For the primary and secondary prevention of cardiovascular disease it is recommended to treat hyperlipidemia along with lifestyle changes. Statins are the first-line drug in treatment of hyperlipidemia associated with cardiovascular disease, but they are reported to be associated with several adverse effects like myopathies, rhabdomyolysis and altered liver function tests.2 Incidence of myopathies and rhabdomyolysis is approximately five in every 1000 patients getting statin therapy. A serious complication of statin-induced myopathy is severe rhabdomyolysis which manifests as high levels of serum creatinine kinase, myoglobinuria and acute renal injury.3 The side effects of drugs result in non-compliance, rendering the treatment ineffective.4 Currently there is growing interest in the use of fruits, vegetables and beverages that contain biologically active phytochemicals and natural antioxidants. Polyphenols are major dietary antioxidant of plant origin present abundantly in fruits, vegetables, legumes and beverages. Apple Cider Vinegar (ACV) is derived from apples that are reported to contain up to 200-300 mg polyphenol per 100-gram fresh weight.5 It was found that as compared to other fruits; apple had the highest portion of free phenolics leading to quick absorption in bloodstream and greater cholesterol-lowering effect.6 Cinnamon is the bark of the Cinnamon tree and being used in traditional and modern medicine and cookery. It is well known for its antioxidant, anti-inflammatory, antidiabetic, anticancer, antimicrobial and lipid-lowering properties.7It contain essential oils and other compounds like cinnamon aldehyde, cinnamic acid, and cinnamate.8 It has been reported that cinnamate is a phenolic compound that inhibit hepatic HMG-Co-A reductase activity leading to lower cholesterol level. It also stimulates antioxidant enzyme activity of liver leading to decrease in lipid peroxidation.9 We hypothesized that the antihyperlipidemic effect of ACV will be increased when given in combination with cinnamon. ACV and Cinnamon have documented antihyperlipidemic effects but their effect in combination was not reported in literature. Therefore, the present study was aimed to find the synergistic effect Cinnamomum cassia and apple cider vinegar on combined administration in albino mice. METHODOLOGY It was an experimental study of one-year duration conducted at the Department of Pharmacology, Al-Nafees Medical College and Hospital, Islamabad in collaboration with Animal House of National Institute of Health, Islamabad, Pakistan. Fifty Balap/c albino male mice, weighing between 20 to 30gms, were used in the study after purchasing them from NIH; Islamabad. The animals were divided into 05 groups, each comprising 10 animals. Before starting the experimentation, the mice were allowed to acclimatize to laboratory conditions i.e. temperature of 22+4 °C for 7 days. Experiment design The experimentation period consisted of 8 weeks divided into two phases: Phase 1: Induction of Hyperlipidemia: Hyperlipidemia was induced during the first two weeks of experimentation. The mice were given normal routine feed mixed with Cholesterol (Applichem, Darmstadt, Germany. CAT No.A08070100) at the rate of 400mg/kg body weight.10During the whole experimentation period mice had free access to feed and drinking water. Phase 2: Treatment period Treatment period consisted of 6 weeks. During this period the mice were given treatment as follows: Group l: Normal Control Mice were given high cholesterol diet during the whole experimentation period from day 1 to 60. Group ll: Treated Control The mice were given high cholesterol diet for first 15 days after which they were given standard lipid-lowering drug i.e. Simvastatin at a dose of 0.6mg/kg BW10 along with high cholesterol diet for next 45 days. Group lll: Treated GroupI The mice were given high cholesterol diet for first 15 days after which they were given Apple Cider Vinegar 15%10 in their diet for the next 45 days. Group IV: Treated Group II The mice were kept on high cholesterol diet for first 15 days after which Cinnamon powder was added in diet at a dose of 6mg/kg BW10 for next 45 days. Group V: Treated Group III The mice were given high cholesterol diet for first 15 days after which they were given a combination of ACV 15% and Cinnamon powder 6mg/kg BW for next 45 days. Blood sample collection Blood samples were collected before start of experimentation and then at 15,30,45,60 days of experimentation. Chloroform was given to anesthetize two mice from each group at the day of sampling. The blood was drawn by direct heart puncturing10 using 3cc disposable syringe and put in vacuum tubes LOT No.1102246. Blood was allowed to clot in a centrifuge tube for 20 minutes and centrifuged for 15 minutes then at 4000rpm, clear supernatant was removed and stored in Eppendorf tubes at -4°C.10 Assessment of lipid profile Total Cholesterol (TC), Triglycerides (TG) and High-density lipoproteins (HDL) were determined using enzyme-based reagent Kits purchased from Merck (Private)Limited. The samples were then analyzed using Automatic chemistry analyzer. Low-density lipoprotein (LDL) was calculated by Friedewald’s formula.11 Statistical Analysis Statistical analysis was carried out using SPSS version 20. Descriptive statistics were calculated. One way ANOVA (Tukey’s test) was applied. p-value Englishhttp://ijcrr.com/abstract.php?article_id=4405http://ijcrr.com/article_html.php?did=4405 Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A et al., Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study2015. The Lancet. 2016;388(10053):1459–44. Gheorghe G, Toth PP, Bungau S, Behl T, Ilie M, Pantea Stoian A et al. Cardiovascular risk and statin therapy considerations in women. Diagnostics. 2020;10(7):483. Karr S. Epidemiology and management of hyperlipidemia. Am J Managed Care. 2017 Jun 1;23(9 Suppl): S139-48. Jacobson TA, Cheeley MK, Jones PH, La Forge R, Maki KC, López JA et al. The Statin Adverse Treatment Experience Survey: Experience of patients reporting side effects of statin therapy. J Clin Lipidol. 2019 May 1;13(3):415-24. Tripathi S, Mazumder PM. Apple cider vinegar (ACV) and their pharmacological approach towards Alzheimer’s disease (AD): A review. Indian J Pharm Educ Res. 2020;54:s67-74. Patocka J, Bhardwaj K, Klimova B, Nepovimova E, Wu Q, Landi M et al. Malus domestica: A Review on Nutritional Features, Chemical Composition, Traditional and Medicinal Value. Plants. 2020 Nov;9(11):1408. Jain SG, Puri S, Misra A, Gulati S, Mani K. Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double-blind control trial. Lip Health Dis. 2017 Dec;16(1):1-1. Lucas K, Fröhlich-Nowoisky J, Oppitz N, Ackermann M. Cinnamon and hop extracts as potential immunomodulators for severe COVID-19 cases. Front Plant Sci. 2021 Feb 26;12:263. KGC D, Liyanage RP, Ranasinghe RH. Traditional Sri Lankan Spices for Dyslipidemia. Iqbal Z, Ashraf T, Khan AA, Hussain R, Mudassar M. Antihyperlipidemic efficacy of cinnamon in albino rats. Asian J Agri Biol. 2016;4(1):8-16. Friendewald WT. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultra-centrifuge. Clin Chem.1972; 8: 499-502. Abdelgadir AA, Hassan HM, Eltaher AM, Khnsaa Mohammed GA, Lamya Mohammed AA, Hago TB. Hypolipidemic effect of cinnamon (Cinnamomum zeylanicum) bark ethanolic extract on triton X-100 induced hyperlipidemia in albino rats. Med Aromat Plants (Los Angeles). 2020;9(351):2167-0412. Packard CJ, Boren J, Taskinen MR. Causes and consequences of hypertriglyceridemia. Front Endocrinol. 2020 May 14;11:252. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eu Heart J. 2017 Aug 21;38(32):2459-72. Okoye NF, Porolo SB. The Effect of Apple Cider Vinegar on the Lipid Profile and Electrolytes of Wistar Rats. J Adv Biol Biotechnol. 2019 May 14:1-1. Abdulrauf RA, Dawud FA, Emmanuel NS, Muhammad HD, Dange AS, David BA et al. Lipid peroxidation and some antioxidant enzymes evaluation in Apple Cider Vinegar (ACV) treated male and female wistar rats exposed to chronic restraint stress. Adv Enz Res. 2018 Sep 14;6(03):21. Launholt TL, Kristiansen CB, Hjorth P. Safety and side effects of apple vinegar intake and its effect on metabolic parameters and body weight: a systematic review. Eu J Nutr. 2020;13(3):1-7. Naz?ro?lu M, Güler M, Özgül C, Saydam G, Küçükayaz M, Sözbir E. Apple cider vinegar modulates serum lipid profile, erythrocyte, kidney, and liver membrane oxidative stress in ovariectomized mice fed high cholesterol. J Memb Biol. 2014Aug;247(8):667-73. Alsoodeeri FN, Alqabbani HM, Aldossari NM. Effects of Cinnamon (Cinnamomum cassia) Consumption on Serum Lipid Profiles in Albino Rats. J Lipids. 2020 Jan 23;2020. Maierean S, Serban MC, Sahebkar A, Ursoniu S, Serban A, Penson P et al. The Effects of Cinnamon Supplementation on Plasma Lipid Concentrations: A Systematic Review and Meta-Analysis. J Clin Lipidol. 2017 Nov 1;11(6):1393-406. Ousaaid D, Laaroussi H, Bakour M, ElGhouizi A, Aboulghazi A, Lyoussi B et al. Beneficial effects of apple vinegar on hyperglycemia and hyperlipidemia in hypercaloric-fed rats. J Diab Res. 2020 Jul 13;2020. Halima BH, Sarra K, Houda BJ, Sonia G, Anis B, Abdallah A. Benefic Effect of Apple Vinegar Cider on Lipid Profile in Streptozotocin-Diabetic Rats. Life Sci J. 2017;14(7). Mateos-Aparicio I, De la Peña Armada R, Pérez-Cózar ML, Rupérez P, Redondo-Cuenca A, Villanueva-Suárez MJ. Apple by-product dietary fibre exhibits potential prebiotic and hypolipidemic effectsin high-fat fed Wistar rats. Bioactive Carbohyd Diet Fibre. 2020 Jul 1;23(1):100219. Petsiou EI, Mitrou PI, Raptis SA, Dimitriadis GD. Effect and mechanisms of action of vinegar on glucose metabolism, lipid profile, and body weight. Nutr Rev. 2014 Oct 1;72(10):651-61. Halima BH, Sarra K, Mohamed S, Louay T, Fethi BS, Houda BJ et al. Apple cider vinegar ameliorates hyperglycemia and hyperlipidemia in Tunisian type 2 diabetic patients. Int J Multidisciplinary Current Res. 2017 Nov;5(2321-3124):1453-9. Panetta CJ, Menk JS, Jonk YC, Brown AJ, Powers MA, Shapiro AC. Prospective randomized clinical trial evaluating the impact of vinegar on high-density lipoprotein. J Am Dietetic Assoc. 2010 Sep 1;110(9):A87. Beheshti Z, Chan YH, Nia HS, Hajihosseini F, Nazari R, Shaabani M et al. Influence of apple cider vinegar on blood lipids. Life Sci J-Acta Zhengzhou University Overseas Edition. 2012;9(4):2431-40. Anderson RA, Zhan Z, Luo R, Guo X, Guo Q, Zhou J et al. Cinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum glucose. J Trad Complement Med. 2016 Oct 1;6(4):332-6. Nikolic T, Zivkovic V, Srejovic I, Stojic I, Jeremic N, Jeremic J et al. Effects of atorvastatin and simvastatin on oxidative stress in diet-induced hyperhomocysteinemia in Wistar albino rats: a comparative study. Mol Cell Biochem. 2018 Jan;437(1):109-18.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcarePursuing Public Health Dentistry as a Career: Motivations and Factors Influencing the Dental Students English3337Rehmatullah KandhroEnglish Khalida Naz MemonEnglish Nimra ZamanEnglish Nida TalpurEnglishIntroduction: A person’s career is the process and actions he or she takes to achieve lifetime goals through his or her occupation. Choosing a career is one of the most important decisions one will ever make. Dentistry yields an extensive scope of career and employment chances as a general professional and specialist Objectives: This study sought the career choices of public health dentistry by dental students and association between socio-demographic profiles of study population with reasons of choosing public health dentistry as a career. Methods: Cross-sectional study conducted atInstitute of Dentistry, Liaquat University of Medical and Health Sciences Jamshoro from 1st March 2021 to 31st May 2021.A sample of 197 undergraduate students were approached using convenience sampling. Data was collected through preformed, validated paper-based survey questionnaire. Association between various socio-demographic variables and career interests of participants was sought by Chi-square tests at 0.05 (2-tailed) level of significance. Results: Around 69.54% of participants belonged to age group of 21-23 years with females accounting for 59.39%. Around 40% participants chose dentistry to please people. A large majority around 62.42% respondents stated that they find public health dentistry an interesting field. Age (p=0.08) and gender (p=0.06) of the individuals were not statistically connected with future career choice in dentistry. Conclusion: Reasons for choosing public health dentistry as a career among the surveyed dental students are mostly related to socio-demographic factors. EnglishCareer, Public health, Public health dentistry, Profession, Dentistry, Public health specialistIntroduction A person's career is the process and actions he or she takes to achieve lifetime goals through his or her occupation.1 Choosing a career is one of the most important decisions one will ever make.2 Dentistry yields an extensive scope of career and employment chances as a general professional and specialist. The choice of dentistry as a profession could offer honor, reputation, self-determination and reward. 3 Dentists inhabited a great status in a healthcare environment as professional care workers.4 Ideally specialists in public health dentistry promote oral health.5 Great attractions have been observed for choosing dentistry as a profession in many areas of the world and a variety of reasons have been attached with this attraction including safety, prestige and ability to have one’s own setup.6 According to studies, students' motivations for choosing dentistry as a career are not constant and are influenced by societal and internal factors. 7 As a general professional and a specialist, public health dentistry develops a wide range of career and business opportunities. In Pakistan, the dental profession lacks curiosity, and academics and research are low on the priority list. 8 Job content, individual stability, personal delight and preference, to become a professional, able to be self-employed, inspired nature of the career, independence, reward in society, and help to the poor are the main reasons for choosing public health dentistry as a profession.9 Several studies have been undertaken to investigate the motivations for choosing dentistry as a career; nevertheless, there is a scarcity of study on public health dentistry, particularly in the context of its selection as a medical profession. Much research has demonstrated that public health dentistry is still in its infancy.3The goal of this study was to learn more about dental students' attitudes toward choosing dental public health as a profession. Therefore, the objectives of the present study were as follows: To investigate the career choices of public health dentistry by dental students immediately after graduation. To seek an association between the socio-demographic profile of the study population with various reasons of choosing public health dentistry as a career. Methods: The study's execution was approved by the LUMHS Ethical Review Committee(letter no: REC/ LUMHS/-40) To reach a sample of 197 undergraduate students studying in a given setting, a convenience sampling procedure was adopted. The survey was conducted using a pre-tested questionnaire. Piloting was used to validate and assess Croanbach’s reliability index, which was calculated as 0.78. The paper-based survey questionnaire, as well as the participants' written informed consents, were distributed in person. The Statistical Package for Social Science (SPSS) software version 23 was used to conduct the statistical analysis. For the categorical variables frequencies were computed. The Chi-square test was used to look for a link between various socio-demographic characteristics and research participants' career interests. The level of significance was set at a 0.05 (2-tailed) p-value. Results A total of 214 dental graduates were approached to get the complete responses of a desired sample size of 197. The response rate was computed as 92.05%. Table 1 shows the socio-demographic distribution of the study subjects. Figure 1 reveals various career options known to the respondents. The response of participants regarding the reasons for selecting dentistry as a career was such that a large majority of participants around40% (80) revealed to choose dentistry to please people whereas 35.5%(70), 18.7%(37) and 5%(10) of respondents chose dentistry for a good future, by chance and by choice respectively. The respondents were asked about their opinion regarding public health dentistry to which 62.42% (123) respondents stated that they find it an interesting field and 28.42% (56) said it is a good profession and 9.13% (18) found it a tedious profession Table 3 and 4 reveals the association of socio-demographic factors of the participants with the career choices in dentistry and opinions regarding public health dentistry respectively. Discussion The choice of a career is a significant decision because it has a significant impact on an individual's future life. 10Not only that, but for strategy makers all over the world, the choice of a certain profession and the attitude of students toward their professional career is critical. 11 In students, the choice of postgraduate specialty and the underlying influencing variables have been studied, but there have been fewer studies on this topic in the Indo-Pakistan subcontinent. Demographic features of a population are major determinants functioning in the background. Any individual's job decision is likely to be influenced by a network of influences that operate before, during, and after graduation. The purpose of this study was to look into the selection of postgraduate specialization made by dental undergraduate students which is affected by various contributing factors. This study examines the attitudes of dental undergraduate students about post-graduation, taking into account their age, gender, and year of study. According to the current study, students who expressed their opinions on dental career persuasion were between the ages of 21 and 23, with a small female preponderance (59.39% females, 40.61% men). As mentioned in table1, 34.78% of students were in their final year of study. This finding was similar to previous studies which reported more than half of the respondents were between the ages of 20 and 23, and that 81.4% of the respondents were females. 12,13,14 Another study conducted in Karachi found that there were more girls than males. 1 a significant chunk of students was enthusiastic about pursuing dentistry and public health dentistry as specialty professions. This was a very positive figure, similar to the findings of a previous study.15 In contrast, a study done in India indicated that just 7% of dentistry students are interested in pursuing a career in public health dentistry.6 A study conducted in Turkey found that 43.2% of undergraduates pick dentistry as their first career choice. 16 While the motivations for selecting dentistry as a profession have been studied in numerous nations around the world such investigations are still limited in Pakistan. 17 According to the study findings, the majority of survey respondents selected dentistry by choice to help others with various dental problems. Furthermore, majority of those polled believe that public health dentistry is an intriguing area to study. This was in stark contrast to previous data, which showed that only 38% of students planned to pursue a specialty career. 18This disparity could be attributable to the fact that only final-year students were selected in the latter study, giving them a more mature perspective on dentistry as a prospective vocation. In a previous survey with similar objectives, 42.45% of the participants chose public health dentistry.19 Year of the study was the most prevalent factor impacting the decision to specialize in dentistry by choice (p=0.05); however, age and gender of the individuals were not statistically connected with future career choices in dentistry (p=0.08 and p=0.06, respectively). A study conducted in Turkey showed no significant results. 16 The majority of the participants thought public health dentistry was a good and engaging field when asked why they picked it as a future career; the results were statistically significant across all strata of the subjects, including age and gender (p= 0.001). The interest of women in dentistry, especially public health dentistry, is comparable to that of populations surveyed in Denmark and Iran 20,21 A study conducted in Riyadh discovered a statistically significant link between students' gender and their intention to seek a future profession in public health dentistry. 22Females were shown to be more interested in working in public dentistry careers than males in a poll performed in Saudi Arabia. 4 While public health was the most popular specialty among individuals, the gender gap was not significant, according to another survey.19 Another study found a highly significant difference between the genders, with more females admitting that not having much 'on-call' work was one of the reasons they selected dentistry as a career. 1 Conclusions This study concluded that among the surveyed dental students, the reasons for choosing dentistry as a career, particularly public health dentistry, are primarily related to socio-demographic factors, with a variety of other factors inspiring dental students to pursue a future public health dental specialty. There are gender differences in career motivations among this group of students, so more research with larger sample size is needed to confirm the trend of change in behavior regarding career choice and associated factors among dental students, as Pakistan is expected to have a high demand for dental postgraduates in the near future. Acknowledgment: 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:No financial support was received Conflict of Interest: The authors declare no conflict of interest Authors’ Contribution: Rehmatullah Kandhro: Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Substantial contribution to the designing, conceptualization, analysis, and interpretation of data for the article. Drafted the article. Writing and editing of the article Khalid Naz Memon: Have contributions in conceptualizing the topic. Validation, Supervision and providing the final approval for the publication of the content. Nimra zaman: Substantial contribution to the designing of the work, analysis and interpretation of data. Drafted the article. Writing and editing of the article. Nida Talpur: Revised it critically for important intellectual content and final approval for the publication of the content. Englishhttp://ijcrr.com/abstract.php?article_id=4406http://ijcrr.com/article_html.php?did=4406 Lone MA, Lone MM, Lone MA, Shaikh MS, Khan F, Comoro AH. Motivational factors for pursuing dentistry as a profession in colleges of Karachi, Pakistan. J Pak Med Assoc. 2020 Mar 28;2020. https://doi.org/10.5455/jpma.33126 Zia S, Abbas M, Sulaiman M, Sheikh SM. Career choices of Medical doctors at Graduate level-A Multicenter Study. Pak J Med Sci. 2017 Sep;33(5):1086.https://doi.org/10.12669/pjms.335.12945 Chandrashekar Janakiram JJ, Antony B. Career satisfaction among dental public health specialists in India–A Cross-sectional Survey.J Clin Diagn Res. 2017 Jan;11(1): ZC97.https://doi.org/10.7860/jcdr/2017/21833.9294 Halawany HS, Binassfour AS, AlHassan WK, Alhejaily RA, Al Maflehi N, Jacob V, et al.  Dental specialty, career preferences and their influencing factors among final year dental students in Saudi Arabia. Saudi J Dent Res. 2017Jan1;29(1):15-23.https://doi.org/10.1016/j.sdentj.2016.12.001 McCunney D, Davis CE, White BA, Howard J. “Preparing students for what lies ahead”: Teaching dental public health leadership with simulated community partners. Indian J Appl Res. 2019 Jul 1. Verma RK, Khare VV, Singh G, Shetty S, Gulia SK, Rajan DT, et al. Evaluation of Choice of Field Post Bds in Dental Graduates–A Questionnaire Study. Ann Rom Soc Cell Biol.2021 Jun 14;25(6):11451-6.https://dx.doi.org/10.11604%2Fpamj.2016.23.22.7381 Alnomay NS, Aldebassi B, Alghomlas AD, Alawad FI, Almutari WM. Choice of Dental Specialties among dental students and associated influencing and motivating factors in Saudi Arabia. J Health Inform Dev Ctries. 2018 Nov 22;12(2). Jawaid SA. Plight of dentistry in Pakistan. Pak J Med Sci. 2020 Mar;36(3):299.https://doi.org/10.12669/pjms.36.3.2278 Nabhan AB, Alshalhoob MA, Almuhaiza KM, Alqwizani ZR. Dentistry as a career: Factors and Motivational Reasons-A Comparative questionnaire study of Students of Public and Private Schools in Saudi Arabia. IAIM, 2018; 5(8): 93-99. https://pesquisa.bvsalud.org/portal/resource/pt/sea-186910?lang=en Gallagher JE, Patel R, Wilson NH. The emerging dental workforce: long-term career expectations and influences. A quantitative study of final year dental students' views on their long-term career from one London Dental School. BMC Oral Health. 2009 Dec;9(1):1-9.https://doi.org/10.1186/1472-6831-9-35 Baharvand M, Moghaddam EJ, Pouretemad H, Alavi K. Attitudes of Iranian dental students toward their future careers: an exploratory study. J Dent Educ 2011; 75: 1489-95. https://pubmed.ncbi.nlm.nih.gov/22058399/ Faisal MR, Mehmood B, Pash L, Siddiqa L. Attitudes of Final-year Dental students towards career development- A cross-sectional survey. JKCD March 2018, Vol. 8, No. 1(101-06). http://www.jkcd.kcd.edu.pk/issues/March-2018-8-1/JKCD-V8-No1-(1).pdf Aguiar CM, Pessoa MAV, Camara AC, Perrier RA, Figueiredo JAP. Factors involved in the choice of dentistry as an occupation by Pernambuco dental students in Brazil. J Dent Edu c. 2009; 73:1401-7. Orenuga OO, da Costa OO. Characteristics and study motivation of clinical dental students in Nigerian universities. J Dent Educ. 2006; 70:996-1003. Hawley NJ, Ditmyer MM, Sandoval VA. Predental students’ attitudes toward and perceptions of the dental profession. J Dent Educ 2008;72(12):1458–64.). ?irino?lu Çapan B., Akyüz S, Bahçecik N, Yarat A, Girgin F. Factors Influencing Career Choices of Dental Students a State University in Turkey Clin Exp Health Sci 2018; 8: 228-236 Maatouk F, El?May W, Ghedira H, Fathallah N. Profile of first-year dental students in Tunisia. East Mediterr Health J 2001; 7:52-9. Puryear J, Kostova V, Kouznetsova A. Final-year dental undergraduate attitudes towards specialization. Dent. J. 2016 Sep;4(3):26.https://doi.org/10.3390/dj4030026 Fidele NB, Kazadi EK, Augustin MM, Mbuebo M, Paul SI, Pierrot KN, et al. The Pre and Final Year Dental Students’ Attitudes, Perception towards Postgraduate Specialization in Kinshasa University—Dental Medicine Department/DR. Congo. Creative Education. 2018 Sep 14;9(12):1808.https://doi.org/10.4236/ce.2018.912131. Vigild M, Schwarz E. Characteristics and study motivation of Danish dental students in a longitudinal perspective. Eur J Dent Educ 20011: 5: 127–133. https://doi.org/10.1034/j.1600-0579.2001.050306.x Khami MR, Murtomaa H, Jafarian M, Vehkalahti MM, Virtanen JI. Study Motives and Career Choices of Iranian Dental Students. Med Princ Pract 2018;17: 221–226. https://doi.org/10.1159/000117796 Alnomay NS, Aldebassi B, Alghomlas AD, Alawad FI, Almutari WM. Choice of Dental Specialties among dental students and associated influencing and motivating factors in Saudi Arabia.  J. health informatics dev. ctries. 2018 Nov 22;12(2).https://www.jhidc.org/index.php/jhidc/article/view/182

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareIris Image Preprocessing and Recognition System English3842R. SrideviEnglish P. ShobanaEnglishIntroduction: Iris recognition framework has gotten vital, particularly in the field of safety, since it gives high reliability. Iris surface is a natural secret phrase that enjoys incredible benefits like inconstancy, soundness, unique highlights for every individual, and its significance in the security field. This makes an iris acknowledgment framework upper of other biometric strategies utilized for human identification. Iris is a hued muscle present inside the eye which helps in controlling the measure of light entering the eye. It has a few extraordinary textural data, which doesn’t get modified or altered effectively, making it a most appropriate quality for biometric frameworks. Because of its uniqueness, all-inclusiveness, unwavering quality, and strength, Iris designs serve a significant job in potential acknowledgment or verification applications. Numerous analysts have proposed new techniques to the iris acknowledgment framework to expand the productivity of the framework. Methods: A total of 460 images were taken into account. First and foremost picture pre-processing is done on the information picture to eliminate undesirable clamor from it and then different segmentation strategies, for example, edge recognition, Camus and Wildes, and so forth are applied for the proficient identification of the inner and outer boundary of the iris. Results: Iris Segmentation was done for MMU Database which contains 460 iris images. Results are recorded. Results from these indicate that it has over Seventy-six percentage. Furthermore, same Wildes methods can be done with different databases like CASIA, IITD, UPOL. Results may vary from MMU database. Conclusion: Our study showed more than seventy-six percentage of success rate for this particular database. Live iris templates also can be obtained and segmentation techniques can be used and find the accuracy. EnglishBiometrics, iris, Segmentation, Iris Recognition, Security, PreprocessingIntroduction The term "Biometric" demonstrates the recognizable proof and confirmation of a person's personality based on interesting highlights or qualities in the people.1Biometric has been generally utilized in a few applications in our everyday life. Biometric is a procedure where an individual will be perceived based on at least one physiological or conduct quality. Biometric frameworks comprise physiological attributes and behavioral qualities.8 Physiological attributes are a gathering of biometrics that incorporate the physiological and biological features as dominated by a biometric framework. It explicitly contains DNA, Hand, Face, Earlobe, and iris. Conduct qualities are a gathering of biometrics that is worried by the non-physiological or non-organic highlights as overwhelmed by a biometric framework. It comprises four classes: Signature, Voice, Gait, and Keystroke acknowledgment.2Iris designs are shaped by joined layers of pigmented epithelial cells, muscles for controlling the pupil, the stromal layer comprising of connective tissue, veins and a front line layer.8,9 One of the critical advantages of biometric security is that it can assist with expanding your protection.17,18 Security is vital in biometrics.13,14 In multimodal biometrics, more than one characteristic of an individual is taken so multimodal biometrics are secure and safe.11,14 The physiological intricacy of the organ brings about arbitrary examples in the iris, which are measurably one of a kind and reasonable for biometric estimations.6 Furthermore, iris designs are steady over the long run and just minor changes happen to them all throughout a person's life.10 The picture of the natural eye may be noisy because of the hypothesis.3 So for the right examination of the picture, unwanted noise should be eliminated to smoothen the picture. For getting a smoothened picture, it should be pre-prepared. Pre-handling includes the utilization of various filters, for example, Gaussian filter, mean filter, middle filter, and so forth for pushing out the undesirable commotion. Image Acquisition An important step in the iris acknowledgment framework is to get a decent and clear picture of the eye. The picture is obtained from an online database of eye pictures. Multimedia University has presented two iris information bases.4 The first is the MMU1 data set which contains 450 pictures, caught by a semi-computerized camera devoted to iris catching (LG Iris Access 2200) at 7-25 cm distance range, furthermore, the subsequent information base is MMU2, comprising of 995 pictures, gathered by Panasonic BM-ET100US camera a ways off the scope of 47-53 cm from the human subject. The pictures in the MMU information base have been gathered from 100 volunteers of various ages and identities, with each volunteer contributing 5 pictures from each eye. Here we have used the MMU1 database. Sample iris images are shown in the figure. Image Preprocessing The picture contains not just the region of interest for example iris, yet it additionally contains different pieces of the eye. Besides, there will be aggravation in the picture if the camera-to-eye distance is adjusted. The brightness additionally plays a significant job as it won't be consistently circulated because of nonuniform enlightenment. Before extracting the feature from the original picture, the picture should be pre-prepared. A. Converting into Gray Image All things considered, we generally get shaded pictures. A few frameworks utilize the RGB Shading model. There are 2 16 or 65,636 potential levels for every essential tone. At the point when the picture is changed over as R = G = B then the picture is known as 16-digit grayscale. This is because the decimal number 65,536 is identical to the 16-digit binary number 1111111111111111. In the 8-bit grayscale picture, the delicacy of the dark is straightforwardly relative to the number addressing the brightness levels of the essential tones. Grayscale is a scope of shades of gray without evident shading. The haziest conceivable shade is black and the lightest conceivable shade is white. Black methods are the complete shortfall of transmitted or reflected light and the white methods are absolute transmission or impression of light at all apparent frequencies. Intermediate shades of dim are addressed by equivalent brightness levels of the three essential tone. B. Image Resizing The picture in the database is resized to the ideal pixel density (256 x 256) to have consistency in the info picture tests. The cropped and the resized picture areas are demonstrated in Figures 2 a and b. C. Smoothing Computerized pictures are inclined to an assortment of noises. Noise is the aftereffect of mistakes that happen during the image acquisition process which brings about pixel values that don’t reflect the intensities of the genuine scene. There are a few different ways that noise might be brought into a picture, depending upon how the picture is made. The most favored way to deal with noise is to smooth the picture. Thus, smoothing channels are utilized for obscuring and noise reduction before attempting to find and distinguish any edges. The Gaussian channel delivers a 'weighted normal' of every pixel's area, with the normal weight more towards the value of the central pixels. This is as opposed to the mean filter's consistently weighted average. Along these lines, Gaussian channels give gentler smoothing and preserve edges better compared to an additional estimated mean filter. The picture after utilization of the Gaussian filter is as demonstrated in figure 3 IRIS and Pupil segmentation The iris and pupil division is a significant step in the iris acknowledgment framework. The segmentation includes different steps to decide the iris and pupil locale in the eye. A. Edge Detection The initial phase in the pre-processing stage is to apply one of the edge recognition procedures to get an edge guide of the iris picture so we can decide all limits of the iris. An edge is a bunch of associated pixels that lie on the limit between two areas in the picture. We can use canny edge detection or Sobel edge detection. The Canny edge detection techniques15 which took into consideration the weighting of the gradients and utilize various stage algorithms to recognize the wide scope of edges are utilized as appeared in figure 4 B. Gamma adjustment To perform further tasks we need to upgrade the contrast of the picture got after edge detection activity. Gamma correction controls the overall brightness of a picture, by changing the sum of gamma amendment there will be a change in the brightness and contrast. Here the gamma esteem in the range 0-1 upgrades the contrast of bright regions and values >1 upgrade the contrast in dark. The value of 1.9 is accepted dependent on best select worth to get great differentiation of iris picture. The pictures after gamma adjustment for the iris are demonstrated in figure 5. C. Hysteresis Thresholding The hysteresis edge was first proposed by John Canny to distinguish edges.16 Hysteresis Thresholdingis a superior option to single static thresholding which is a dynamic thresholding technique. In hysteresis Thresholding we use two limits esteems th the high edge esteem and tl as the lower limit esteem where th> tl. Pixel esteems that are over the th esteem are promptly named edges. The adjoining pixel esteems with slope greatness values not as much as th can likewise be named edges as long as they are over the lower limit esteem tl. This measure eases issues related to edge discontinuities by distinguishing solid edges and protecting the significant powerless edges, keeping up some degree of noise concealment. If pixel (x, y) has slope size among tlow and thigh and any of its neighbors in a 3×3 region around it have slope sizes more noteworthy than thigh, at that pointed edge are assumed. The picture after hysteresis thresholding is applied to the iris is demonstrated in figure 6. Segmentation Camus and Wildes5 depicted a calculation for finding a subject's iris in a nearby picture. In a manner like Daugman's strategy6, their calculation looks in an N3 space for the three perimeter boundaries (center (x, y) and radius z) by expanding the accompanying work. Where n is the absolute number of directions and Iu,r, and gu, rare, individually, the picture intensity and derivatives concerning the radius in the polar coordinate framework. This strategy is extremely exact on pictures where the pupil and iris locales' forces are isolated from the sclera ones and on pictures that contain no reflections or other noise factors. When managing noisy information, the calculation's exactness deteriorates essentially.7The picture after segmentation for the iris are demonstrated in figure 7. Normalization Normalization refers to setting up a portioned iris picture for the element extraction measure. In Cartesian directions, iris pictures are exceptionally influenced by their distance and precise position concerning the camera. In addition, light straightforwardly affects pupil size and causes non-straight varieties of the iris designs. The picture after normalization for the iris are demonstrated in figure 8. Matching The matching stage is a cycle to compute the level of likeness between the info test picture and the training picture from the data set. The component vectors are characterized through various edge strategies like hamming distance, weight vector and winner selection, dissimilarity function, and so forth in this work hamming distance approach is utilized to think about the information and the layout by utilizing Hamming Distance equation which given by Equation Where CA and CB are the coefficients of two iris pictures, N is the size of the element vector, Ex-OR is the Boolean administrator that gives a binary 1 if the pieces at the position j in CA , CB are extraordinary and 0 in the event that they are comparable. In the event that HD Threshold, non-Match pair. Implementation and Results We have selected MMU database and 460 samples have been taken into account. With these data samples, we are going to do an experiment. The False Reject Rate (FRR), False Accept Rate (FAR) are the two measurements that are been utilized to quantify the achievement of the coordinating with rate. True Positive Rate measures the extent of positives that are effectively recognized. For example the extent of the individuals who have some condition who are accurately recognized as having the condition. True Negative rate gauges the extent of negatives that are effectively distinguished for example the extent of the individuals who don't have the condition (unaffected) who are accurately recognized as not having the condition. For the considered MMU Database, Both True Positive Rate and True Negative Rate are calculated. As a result, we got TPR as 75% and TNR as 33%. True Positive Rate is calculated as, TP/TP+FP, and True Negative Rate is calculated as, TN/TN+FP. Accuracy was calculated for the given dataset. The result is given in Table 1. Discussion The outcome of this study indicates that using the Wildes Segmentation technique on MMU Database got only 76% accuracy. For this study, we chose MATLAB for our implementation purpose. It incorporates calculation, representation, and programming in a simple to-utilize environment where issues and solutions are communicated in familiar numerical notation.  In the future, the same segmentation technique can be used for different databases like IITD, UBOL, and CASIA and check the accuracy for iris images. Live iris templates also can be obtained and segmentation techniques can be used and find the accuracy. Conclusion Appropriately identifying the inner and external limits of the iris surface is significant for all iris acknowledgment frameworks. The unpredictable limit of the pupil was the inspiration of planning an active contour for distinguishing the limit precisely. The dynamic shape takes into a thought that a genuine pupil limit is a near-circular contour instead of an ideal circle. This technique effectively distinguishes all the pupil boundaries in the MMU1 information base furthermore, improves the acknowledgment results. In this paper, the iris acknowledgment measure is led step by step. Gather the iris picture and do preprocess on iris picture which the objective to eliminate undesirable information which incorporates the segmentation, step then pupil limit distinguish step and Normalization. The future work of this paper might be to reach out to examine distinctive component extraction strategy and matching technique that improves the exhibition of iris acknowledgment framework Acknowledgment Authors acknowledge the immense help received from the scholars whose articles are cited and included in the references of this manuscript. The authors are also grateful to the 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: None declared Source of funding: No fund was received for this study Authors Contribution: Dr. R. Sridevi, P. Shobana conceived and planned the experiments. P. Shobana carried out the experiments. Dr.R.Sridevi verified the analytical methods and supervised the findings of this work. All authors discussed the results and contributed to the final manuscript. Englishhttp://ijcrr.com/abstract.php?article_id=4407http://ijcrr.com/article_html.php?did=44071. Kharat P, Deshmukh M. Iris Recognition: a Review. Int. J. Adv. Trends Comput. Sci. Eng. . 2013: 93-97. 2. Jain A, Ross AA, Nandakumar K. Introduction to Biometrics. 2011. 3. Mahmoud M, Ali N. Human Iris Segmentation for Iris Recognition in Unconstrained Environments.Int. J. Comput. Sci.2012;9: 149-152. 4. Multimedia University Iris Database (MMU) - V1 and V2 https://mmuexpert.mmu.edu.my/ccteo 5. Camus TA, Wildes R.Reliable and fast eye finding in close-up images. IEEE 16th Int. Conf. on Pattern Recognition., Quebec, Canada. 2004: 389–394. 6. Daugman JG. High confidence visual recognition of persons by a test of statistical independence.IEEE Transactions On Pattern Analysis and Machine Intelligence. 1993; 15(11):1148–1161. 7. Hugo P. Towards Non-Cooperative Biometric Iris Recognition. PhD thesis, University of Beira Interior, October 2006. 8. Wildes R. Iris Recognition: An Emerging Biometric Technology. Proceeding of the IEEE. 1997; 85(9). 9. Adler FH. Hysiology of the Eye. St. Louis, MO: Mosby. 1965 10. Flom L, Safir A.Iris recognition system. U.S. Patent 4 641 349. 1987. 11.  Sridevi R, Shobana P. Multimodal Security of Iris and Fingerprint with Bloom filters. AEGAEUM Journal. 2020; 8(10). 12. Sridevi R, Shobana P. Security and Accuracy of Iris-based Biometrics – A Review.DogoRangsang Research Journal, 2020; 10(12). 13.  Gobi M, Sridevi R. An Approach for Secure Data Storage in Cloud Environment. International Journal of Computer and Communication Engineering(IJCCE).2013; 2(2). 14. Gobi M, Sridevi R.Multi-Biometric Authentication through Hybrid Cryptographic System.  International Journal of Computing Algorithm[IJCOA].2015; 14(1). 15. Tania UT.Edge detection techniques for iris recognition system.IOP Conference Series: Materials Science and Engineering. 2013. 16. Canny J. A Computational Approach to Edge Detection. IEEE Transaction on Pattern Analysis and Machine Intelligence.1986:679-714. 17. Gobi M, Sridevi R. Biometric Security based on Reversible Data Hiding with RZL Code and Elliptic Curve Cryptography.American International Journal of Research in Science, Technology, Engineering & Mathematics (AIJRSTEM) 2015; 10. 18. Gobi M, Sridevi R. A Secured Asymmetric Cryptosystem for Multi-Biometric Security. Int. J. Trend Res.2015; 2(5).

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15Healthcare Emerging Implementation of Nano-Suspension Technology for Delivery of Poorly Soluble Drug for the Treatment of Helminths Disease English4350Shubhrajit MantryEnglish Shubham ShindeEnglish Sahil ShaikhEnglish Sumit JoshiEnglish Ganesh DamaEnglish Anthelmintics are medications that are used to treat parasitic worm infections. This comprises flatworms like flukes and tapeworms as well as roundworms like nematodes. They are critical for human tropical medicine. Nano-suspensions are one of the many applications of nanotechnology. Nano-suspensions are liquid formulations that feature submicron colloidal dispersion of pharmaceutical active component particles stabilised by surfactants. Nano-suspension technology is a novel and cost-effective method for improving the bioavailability of hydrophobic medicines, particularly those that are poorly soluble in aqueous solutions. Nano-suspensions play a significant role in the development of new medication formulations. High-pressure homogenizers, emulsion solvent evaporation, melt emulsification technique, and nanoprecipitation are all used to make nano-suspensions. Particle size, zeta potential, drug content, and in vitro drug dissolution were all examined for the nano-suspensions. Poorly soluble drugs can benefit from nano-suspension technology to improve their stability and bioavailability. The bioavailability of nano-suspension was also tested in mice, which showed that the particle size distribution of nano-suspension was considerably affected by bioavailability. The rate of anthelmintic nano-suspension dissolution was substantially higher than that of raw drug powder. In vivo pharmacokinetic characteristics of nano-suspension indicated a substantial increase in Cmax and AUC(0-t) when compared to pure drug. When compared to pure drug bioavailability, anthelmintic nano-suspension had a greater oral bioavailability. EnglishHelminths, Nano-suspension, Parasites, Bioavailability, In vitro study, Solubility Introduction- A parasitic disease is an infectious disease caused or transmitted by a parasite. Various parasite does not cause diseases as it may eventually lead to the death of both the organism and host. Parasites infecting human being are also called as human parasites. The study of parasitic disease is called as parasitology.1 Parasitism is a sort of antagonistic cohabitation in which one organism gains while the other suffers harm. Parasites have evolved a variety of adaptations to their hosts in order to maximize their benefits. 1 Nano-suspensions are colloidal dispersions and biphasic systems made up of drug particles suspended in an aqueous medium with a diameter smaller than 1 micrometer. A good size-reduction procedure and a suitable stabilizer can be used to make nano-suspension.2 The particle size in the nanometer range can contribute to higher dissolution velocity and saturation solubility for a nano-suspension, according to Noyes Whitney and Ostwald Freundlich principles, which is usually followed by an increase in bioavailability.2 History- The first written accounts of what are almost probably parasite diseases are from the Egyptian medical period between 3000 and 400 BC, specifically, the Ebers Papyrus discovered at Thebes in 1500 BC. Humans have acquired an incredible number of parasites over our comparatively short history on Earth, including roughly 300 species of helminth worms and over 70 species of protozoa.3 S. Runge's first nanocrystal formulation (Runge 1998) did not produce the theoretically expected increase in bioavailability. In contrast to earlier evidence that nano-suspensions increase bioavailability for example, from 5% to roughly 80%.4 Nanotechnology is a subset of nanoscience, which is one of the most promising, hard, and exciting research areas in today scientific landscape. It is the study of small particles with unique features that change as the particle size changes.5 Parasitism is a complex phenomenon involving three subsystems: the parasite, the host, and the environment. The system evolved together, but modifications in any subsystem might produce disruptions, resulting in disease. Parasites are found in all creatures. Parasitism is a phenomenon that began to emerge at the same time as life on Earth.6 Types of parasites- 1) Flukes(Trematodes)- Adult flukes are flatworms with a leaf-like form. The presence of prominent oral and ventral suckers aids in keeping the position in place. Except for blood flukes, which are bisexual, all flukes are hermaphroditic. A snail serves as an intermediary host in the lifecycle. 2) Tapeworms (Cestodes)- Tapeworms are hermaphroditic flatworms that live in the intestinal lumen and are elongated, segmented, and hermaphroditic. Extraintestinal tissues are home to cystic or solid larval stages. 3) Roundworms (Nematodes)- Adult and larval roundworms are bisexual, cylindrical worms. They inhabit intestinal and extra-intestinal sites 7 Application of Nano-suspension- Nano-suspension has shown the ability to alleviate the issues associated with the delivery of poorly water-soluble and poorly lipid-soluble medicines by reducing particle size and increasing surface area. The nano-suspension DDS has been widely used in the areas of oral, pulmonary, parenteral, and ocular drug delivery, and has shown to be superior to standard drug administration routes. 1) Oral drug administration- The oral administration method is chosen over the many alternative drug delivery administration routes due to the numerous advantages it offers. Safety, good patient compliance, ease of intake, pain prevention, and versatility to handle various types of medications are just a few of the benefits. The use of nano-suspension DDS to increase the bioavailability of poorly soluble medicines is advantageous. The many advantages of nano-suspension DDS for oral administration, such as enhanced dissolution rate and solubility of poorly soluble drugs, high adhesiveness of drug nanocrystals on the epithelial gut wall, prolonged absorption time of drug nanocrystals due to long gastrointestinal tract, and reduced variability caused by food, are the main reasons. Oral administration can be done using both liquid and solid dose forms, such as powder, tablet, pellet, capsule, and film. The prepared liquid nano-suspensions can be directly utilized in liquid dosage form for oral administration.16 2) Parenteral Administration- In emergency cases such as cardiac arrest and anaphylactic shock, parenteral injection is favored above alternative drug administration routes. This method of administration has various advantages, including avoiding first-pass metabolism, improved bioavailability, and consistent dose. Parenteral administration has more control over the dose and rate than oral administration, resulting in more predictable pharmacodynamics and pharmacokinetic characteristics. The size of medication particles supplied should be less than 5 m in order to minimize capillary obstruction. When compared to the standard form of Oridonin, a study on the potential of Oridoninnano-suspension to inhibit tumour growth found that Oridonin in the form of nano-suspension can considerably increase the rate of tumour suppression by approximately 20%. With the use of nano-suspension, therapy efficiency is improved while costs are considerably decreased.16 3) Pulmonary Drug Delivery- Nano-suspensions can be nebulized for pulmonary administration using mechanical or ultrasonic nebulizers. All aerosol droplets include drug nanoparticles due to the existence of many tiny particles. Because the particle size is so small, aqueous preparations of the medication can simply be nebulized and administered via the pulmonary route. For the delivery of liquid formulations, a variety of nebulizers are available.14 4) Ocular Drug Delivery- Nano-suspensions are employed in ocular medicine delivery for long-term release. It revealed that the medication was more readily available in the rabbit eye's aqueous fluid. As a result, nano-suspension formulation appears to be a potential technique to extend the shelf life and bioavailability of drugs following ocular administration.14 Histopathology- Histopathological investigation is critical in the identification of infectious, neoplastic, parasite, deficient, and intoxication illnesses in humans and animals. Parasitic disorders are frequently misdiagnosed 8 Histopathological study reveals pathogen-pathogen interactions and their impact on the host organism. Histopathological changes during parasitic invasions are particularly essential for differential diagnosis and frequently establish the existence of parasitic illnesses.8 The main objectives is to determine the function of histopathology in the diagnosis of animal parasitic diseases and to uncover pathological changes that occur during invasions induced by several parasite taxa, including the Protozoa, Trematoda, Cestoda, Nematoda, Acari, and Insecta.8 Mechanisms of anthelmintic resistance- The mechanisms and genetics of anthelmintic resistance are critical in efforts to overcome resistance, slow the spread of resistant parasites, delay the development of resistance to new anthelmintic drugs, and better manage parasite control, including the use of anthelmintic combinations with existing anthelmintic. 9 On the basis of their mode of action, most anthelmintics can be divided into two groups. Drugs that impact the parasite's energy generation and drugs that disrupt the parasite's neuromuscular system (Paralysis). The neuromuscular system is affected by anthelmintic. Neurotransmission destruction is inhibited, or the action of neurotransmission is enhanced, or the activity of neurotransmission is antagonistic. The parasite is eventually paralyzed, either spastic or flaccid. The host peristaltic movement expels the paralyzed parasite.9,21 Figureno.2:Schematic representation of different factors which could affect the action of an anthelmintic, leading either to death of the target parasite or to anthelmintic resistance. Recent advances in nano-suspension for the treatment of helminthic disease- Parasitic infections are found throughout the animal species and have developed alongside Homo sapiens for millions of years. Helminth parasites were first documented in Egyptian papyri between 3000 and 400 BCE, and later in Greek and Arabic medical publications. Humans are home to more than 70 protozoa species and 300 helminth worm species, yet just a small percentage of them are responsible for the majority of human sickness. Anthelmintic resistance is a heritable alteration in a worm population that allows them to withstand pharmacological treatments that are normally successful against the same species and stage of infection at the same dose rate. Imidazothiazoles (e.g., levamisole), tetrahydro pyrimidines, quaternary ammonium salts, and pyrimidines are anthelmintics that target nAch receptors. The nAch receptor on nematode body muscle is the target of these structurally related anthelmintics. Binding to the receptor recognition site produces nematode muscle depolarization and spastic paralysis, which results in parasite ejection. Some anthelmintic drugs act rapidly and selectively on the neuromuscular transmission of nematodes. Levamisole, pyrantel and morantel are agonists at nicotinic acetylcholine receptors of nematode muscle and cause spastic paralysis. Anthelmintics work by preventing worms from absorbing the sugars that they require to survive. The worms are killed, but not the eggs. Praziquantel and ivermectin operate by paralyzing intestinal worms (intestine). anthelmintic resistance (AR) as a genetically transmitted loss of drug sensitivity in worm populations that had previously been responsive to the same treatment Alleles coding for resistance will exist in a worm population as a result of mutations, even in populations that have never been exposed. Anthelmintic medicine it stops freshly hatched insect larvae (worms) from reproducing or expanding in your body. Anthelmintic category drug is used to treat worm illnesses like swine tapeworm and dog tapeworm. So, in this parasitosis disease, the anthelmintic reduces the activity or stop the glucose production for the growth of parasite worm infection. They have paralyzed the parasites present in a particular cell. Anthelmintic Nano-suspension includes smaller particle size for greater solubility and bioavailability and shows good therapeutic effects. 10 Causes of parasitic infections- Parasitic infections can be caused by three types of organisms: 1) Protozoa 2) Helminthes 3) Ectoparasites Infections caused by parasites can be transmitted in a variety of ways. Protozoa and helminths, for example, can be passed from person to person through polluted water, food, waste, soil, and blood. Some of them can be spread from one person to the next through sexual contact. Insects that act as disease vectors (carriers) transfer some parasites. Helminths are multicellular organisms that can live both within and outside your body. Worms are a more frequent name for them. Flatworms, tapeworms, thorny-headed worms, and roundworms are some of them. 11 Role of nano-suspension in helminthic infection- The use of a high-speed homogenizer and ultrasonication technology to make polymeric-coated nano-suspension boosts the drug solubility and absorption rate, increasing its availability at the site of action and increasing its bioavailability. In this study, we create a polymer-coated drug nano-suspension, which increases therapeutic efficacy by limiting particle size availability. The rate of absorption in the stomach and intestine increases by using a polymer coating formulation. In parasitosis diseases, the anthelmintic drug inhibits the production of Glucose for growth and development of worm infection and it can paralyze the worms in the gut (intestine). Nano-suspensions were prepared using the precipitation-ultra sonication method using suitable stabilizers and high-pressure homogenization for poorly soluble drugs. By the help of Ultrasonic homogenizers are very efficient for reducing particle size in small shapes. Cavitation is used to homogenize the fluid. Sound waves propagate through liquids when they are exposed to severe ultrasonication, creating alternating high-pressure and low-pressure cycles. Nano-suspension technology has shown to be a novel and profitable method for increasing the bioavailability of poorly soluble medicines. Nano-suspension is a biphasic dispersion of very fine colloidal solid medication particles in an aqueous medium stabilized with surfactants. The most important advantages of polymer-coated drug nanoparticles is to enable controlled release to the desired region, to provide stability to labile molecules (such as proteins), and to provide the ability to change surfaces with ligands for stealth and targeted drug delivery. The rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action is known as bioavailability.12 Role of additives for nano-suspension drug targeting- Polymer- For the purpose of controlled release to the appropriate region, provide stability to labile molecules, to allow for the modification of surfaces with ligands for stealth and targeted drug delivery. Eg. Gelatin, lecithin, nylon, polyethylene, and polyester. Organic Solvent- Organic solvents include aliphatic hydrocarbons, aromatic hydrocarbons, amines, esters, ethers, ketones, and nitrated or chlorinated hydrocarbons, among others. Eg- Methanol, Ethanol, Chloroform, Isopropanol, Ethyl acetate, Ethyl formate, Butyl lactate, Stabilizer- Wet the drug particle and prevent agglomeration of Nano-suspension and also providing a steric or ionic barrier. Stabilizer plays an important role in the formulation of nano-suspensions. In the absence of an appropriate stabilizer, the high surface energy of nano-sized particles can induce agglomeration or aggregation of the drug crystals. The main function of a stabilizer is to wet the drug particles thoroughly and to prevent Ostwald ripening and agglomeration of nano-suspensions in order to yield a physically stable formulation by providing steric or ionic barriers. Eg- Lecithin, PVA (polyvinyl alcohol), PVPK-30(polyvinyl pyrrolidone) Surfactant- The surfactant lowers the mean particle size by modulating the accessible surface energy of the particles. As a result, the surface tension falls and the Kelvin barrier shifts, allowing more particles to escape the aggregation process. Eg-Tweens and spans. e) Co-surfactants- Cosurfactant can have a big impact on phase behavior, it crucial to look into how they affect internal phase uptake for different microemulsion compositions and drug loadings. While the use of bile salts and dipotassium glycyrrhizinate as a Cosurfactant is described in the literature, various solubilizers can also be employed safely as Cosurfactant in the microemulsion production process. e.g. Transcutol, glycerol, ethanol and isopropanol safely used as co-surfactants. Also, bile salts and Dipotassium glycyrrhizinate can be used as co-surfactants. Buffer- To maintain pH of formulation within normal range. Eg-Acetate Phosphate. Cryoprotectants  Cryoprotectants are substances that protect biological tissue from the effects of freezing (i.e., due to ice formation). Cryoprotectants are also utilized in the study of biology to preserve living things and in the preservation of food. Eg. - Sucrose. Aq. Solvent  For the dissolution of surfactant form solution the aq. Solvent use Eg. Water. Drug- Depending on category purpose of use of medicine the selection of drug take place13  Production technique used in the preparation of Nano-suspension- A) Bottom-up techniques- It is a method of obtaining nanoscale particles by increasing particle size from the molecular to the nanoscale. Bottom-up technology refers to the traditional processes of precipitation (Hydrosol). The medication is dissolved in an organic solvent and then combined with a miscible anti-solvent using a precipitation process. The solubility of the medication in the water-solvent mixture is low, and the drug precipitates. The basic challenge is that the growth of the crystals during the precipitation phase must be regulated by adding a surfactant to avoid the creation of microparticles.14 B) Top-down techniques- The techniques in which the nano-size range of particles is obtained by reduction in size of larger particles. 1) High-pressure homogenization (DissoCubes)- 2) Media milling (NanoCrstals) 3) Homogenization in non-aqueous media (Nanopure) 4) Combined precipitation and homogenization (Nanoedge) 5) Nanojet Technology 1) Nanoprecipitation- Drug (10 mg) was dissolved in 5 ml of water-miscible solvents like acetone or ethanol. This was added dropwise to 10 ml of aqueous surfactant solution (0.5 % of poloxamer 188 or polysorbate 80 or sodium lauryl sulphate) with stirring. The resultant mixture was sonicated for 5 min followed by stirring on magnetic stirrer till the organic solvent was completely evaporated 15 2) High-pressure homogenization- There are two types of high-pressure homogenization that are categorized as dissocubes and nanopore. The homogenization of disco cubes takes place in aqueous fluids, whereas the homogenization of nanopure takes place in water mixes or nonaqueous media. The nanopore method, which is carried out at low temperatures and is also known as the deep freeze method, is another high-pressure homogenization process. Because of the low vapour pressure of oils or oily fatty acids and their high boiling point, cavitation does not develop when drug nanocrystals are disseminated in water mixes or non-aqueous media 16 3) Milling- Drug (10 g) and sodium lauryl sulfate (1.0 g) were taken in a cylindrical stainless-steel vessel (high shear ball mill) and mixed with 3 balls (1.0 mm) and 3 balls (2.0 mm) made of zirconium oxide and subjected to high shear rotations. Milled powder samples (6  12 hr) were triturated in water to get aqueous dispersions. The obtained dispersions were subjected to sonication (10 min) and analyzed for mean size using Malvern Zetasizer. 15 4) Sonication- To create a homogeneous dispersion, drug (1.0 g) and surfactant (0.5 %) were combined and triturated in water (25 ml). In the case of polymer-containing formulations, an aqueous solution of the polymer was used. To obtain a consistent product, it is prepared and triturated with medication and surfactant. Dispersal. The resulting dispersion was ultrasonicated (12T- probe) For 5 and 10 minutes, I used a Sonopuls Ultra homogenizer (Bandelin, Germany) for 5 and 10 minutes. 15 Characterization of Nano-suspension- 1) Morphological study- Transmission electron microscopy was used to examine the morphology of drug nanocrystals in their ideal state (TEM) They discovered that the particles are spherical in shape, with a smooth surface and no rough pores. The majority of the particles are of the same in colour, indicating that electron intensity was high.17 2) Determination of zeta potential- The nano-suspensions of zeta potential were determined using an extra electrode in the same device that was utilized for particle size analysis (Malvern Zetasizer). The electrophoretic mobility was translated to zeta potential using the Smoluchowski equation as samples of formulations were diluted with water and placed in the electrophoretic cell. At 25°C, each sample was measured three times, with the average values determined. 12 3) Particle Size and crystalline state Analysis- Dynamic light scattering was used to determine the size and polydispersity index (the width of the particle size distribution) of nano-suspensions (Zetasizer Nano ZS, Malvern Instruments, Ltd.).The crystalline state analysis is important to study the number of amorphous drug nanoparticles within the nano-suspensions since they are likely to be produced during the preparation of nano-suspensions. These are observed by using XRD and scanning electron microscopy. 12,16 4) Saturation Solubility and Dissolution Velocity- Saturation solubility and dissolution velocity are two significant metrics that can be used to examine changes in drug bioavailability, plasma peak, and blood profile in vivo. Because a nano-suspension is usually employed to boost the drug's saturation solubility, it's important to look into its saturation solubility. Furthermore, the dissolving velocity is a significant metric for nano-suspension, demonstrating their advantages over traditional formulations. As a result, it's important to test the drug nanosuspension saturation solubility and dissolution velocities in various conditions, such as different physiological buffers and temperatures.16 5) Determination of Drug Content- Dissolving 10 mg of each sample in 5 mL ethanol was used to conduct the analysis. The samples were vortexes for 1 minute at room temperature, filtered (0.45 µm, Millipore), and one mL of water was added. The amount of medication was measured using a spectrophotometric method (Perkin Elmer, Japan) at 279nm against a blank of water.2 6)Statistical analysis- The arithmetic means and standard deviation of particle sizes are presented. A two-way analysis of variance was performed to evaluate statistically significant differences in the influence of stabilizers and techniques on mean particle size (ANOVA). The 0.05 level of probability was used to test significance. The SPSS software suite was used for statistical analysis. 6 7) Differential Scanning Calorimetry (DSC)- The thermo-tropic phase transition behavior is quantified using DSC. DSC thermograms of pure drug, pure Poloxamer, and their proposed nano-suspension. The formulation of pure drug and pure Poloxamer have sharp endothermic peaks at wavelength 216°C and 55.95°C, respectively. The representative nano-suspension formulation, on the other hand, did not produce a pronounced endothermic peak. As a result, the absence of a drug endothermic peak in the thermogram indicates that the drug was mostly changed from crystalline to amorphous during the manufacture of nano-suspension using the anti-solvent precipitation method or during freeze drying of nano-suspension. It's worth noting that each polymorph of medicine has its own melting and transitioning tendencies as a significant by-product of photochemical or thermal degradation. 18,13 Dissolution Study- The USP Apparatus II (paddle method) was used to investigate the dissolution of nano-suspension formulations at a paddle speed of 75 rpm, a temperature of 37°C0.5°C, and a dissolving medium of 0.1 N hydrochloric acid (pH=1.2). The rate of dissolution of nano-suspension was compared to that of raw powder. After adding the formulations to the dissolution vessels, a pipette was used to collect samples (5mL) at 0, 5, 10, 15, 30, and 60 minutes. UV spectroscopy was used to examine samples that had been filtered with a 0.22 m Millipore filter (Whatman, UK) and were analyzed by UV (277nm). After each sample removal, 5ml of fresh dissolving medium was added.13,18 Animal Study- Anti-Helminthic activity for the helminthic disease- An anti-helminthic medicine is a substance that kills or makes parasitic intestinal worms expel themselves. Vermifuges (stunning) or vermicides are other names for them (killing). The anthelmintic activity of the produced formulation against P. posthuma was examined. Six sets of six earthworms were discharged into 50 mL solutions containing three different drug formulation concentrations (25, 50, and 100 mg/mL each). The standard reference was Albendazole at the same concentration as the extracts, and the control was distilled water. Individual worms were timed to see how long it took them to become paralysed and die. When there was no movement of any kind except when the worms were shaken vigorously, that was the time for paralysis. The worms were declared dead when they did not move when shook vigorously or when submerged in warm (50 °C) water, and their body colours faded19 In vivo pharmacokinetic studies- The Institutional Animal Ethics Committee (AISSMS/IAEC/18-19/1-20) granted authorization for the animal investigations. Male Wistar rats weighing 250–300g fasted for 24 hours while having unlimited access to water. The rats were divided into three groups of six rats each, with the control group receiving only plain vehicle, the second group receiving a marketed suspension, and the third group receiving manufactured suspensions orally via a feeding tube (equal to 50mg/kg dosage). Blood was collected from the retro-orbital vein at intervals of 1,2,4,6,8, and 10 hours and examined using reverse-phase high-performance liquid chromatography. The rats in each group were euthanized after 10 hours, and their intestines were separated and drug content was evaluated 18. Pharmacodynamic study/Bioavailability study- Male Swiss albino mice were used for the bioavailability investigation. The bioavailability of the nano-suspension formulation was compared to that of a micro-suspension made in-house with raw drug powder. The mice were fasted overnight before dosing but given unrestricted access to water throughout the experiment. They were then randomly assigned to one of two groups: nano-suspension (group A) or micro-suspension (group B) in a crossover design. Gavage was used to administer both the nano-suspension formulation and the powder (suspended in saline) at a dose of 1.4 mg/kg of mice. At five different time intervals (10, 20, 30, 40, 60, 80 min), blood samples (200 µl) were taken from a cannula vein containing citrate buffer. Tubes containing heparin Plasma was isolated from blood samples by centrifugation at 2500g for 10 minutes and kept at 20 °C until analysis. 18 Pharmacokinetic data analysis- The pharmacokinetic behavior of an anthelmintic medication was studied using a non-compartmental pharmacokinetic approach. PK solver was used to determining the pharmacokinetic parameters (Microsoft Excel). The linear trapezoidal approach was used to determine the area under the plasma concentration-time curve (AUC). Using the same dose level (1.4 mg/kg), the relative bioavailability (BA) of the Anthelmintic nano-suspension compared to the control micro-suspension was computed as follows: AUC/AUC is the relative BA percent. T = 0.693/K was determined as the apparent elimination half-life. Following oral delivery, the maximum plasma concentration (C) and time to maximum concentration (T) were calculated directly from the data.13 Discussion- According to evaluations of multiple papers, reducing the particle size of the dosage form increases porosity and permeability, which increases bioavailability and therapeutic efficacy, and this phenomenon is useful for treating worm infection. Anthelmintic are the best category of the drug in polymeric nano-suspension form, according to the review, and produce better results than other drug categories. When standard dose forms are compared to novel drug delivery systems (NDDS) dosage forms, we discover that NDDS is more effective and patient compliance is higher. Conclusion- In polymer coated Nano-suspension we increased their solubility, Bioavailability and dissolution time by reducing their particle size and it also shows the helminthic effect. In the conventional dosage form of suspension they have less solubility and less dissolution rate due to their improper particle size and size variation they directly effect on their solubility property so high-speed homogenization and sonication is the best way to overcome this problem. This anthelmintic nano-suspension work on parasitic infection to kill or paralysed the worm present in the intestine. The polymer-coated Nano-suspension are show the good therapeutic effect and greater bioavailability. Acknowledgment- The authors express their heartfelt gratitude to Sharadchandra Pawar College of Pharmacy, Dumbarwadi, Otur, the college library, and all other sources for their cooperation and guidance in writing this review article. Source of Funding - There is no any source of funding for my review study. Conflict of Interest- There are no conflicts of interest and disclosures regarding the manuscript. Authors’ Contribution-The concept and Design of the study were done by Shubham Shinde, Shubhrajit Mantry. Data acquisition and analysis were done by Shubham Shinde. Manuscript preparation, editing done by Shubham Shinde. Englishhttp://ijcrr.com/abstract.php?article_id=4408http://ijcrr.com/article_html.php?did=4408 1.        Cholewiski M, Derda M, Hada E. Parasitic diseases in humans transmitted by vectors. Ann Parasitol. 2015;61(3):137–57. 2.        Afifi SA, Hassan MA, Abdelhameed AS, Elkhodairy KA. Nano-suspension: An emerging trend for bioavailability enhancement of etodolac. Int J Polym Sci. 2015;2015. 3.         Cox FEG. History of human parasitology. Clin Microbiol Rev. 2002;15(4):595–612. 4.        Sawatdee S, Atipairin A, Yoon AS, Srichana T, Changan N, Suwandecha T. Formulation development of albendazole-loaded self-micro emulsifying chewable tablets to enhance dissolution and bioavailability. Pharmaceutics. 2019;11(3). 5.        Chandra A, Kumar Soni R, Sharma U, Jain SK. NANO-SUSPENSION: AN OVERVIEW. J Drug Deliv Ther. 2011;2013(3):162. 6.        Araújo A, Reinhard K, Ferreira LF, Pucu E, Chieffi PP. Paleoparasitology: The origin of human parasites. Arq Neuropsiquiatr. 2013;71(9 B):722–6. 7.        Geerts S, Gryseels B. Drug resistance in human helminths: current situation and lessons from livestock. Clin Microbiol Rev. 2000;13(2):207–22. 8.     Soltysiak Z, Rokicki J. Histopathological diagnosis in parasitic diseases Anisakidae taxonomy and phylogeny View project Phylogeny of Contracaecum family View project 73 PUBLICATIONS 271 CITATIONS SEE PROFILE. Ann Parasitol. 2014;60(2):127–31. 9.        Vanden Bossche H. Studies of the mode of action of anthelmintic drugs: Tools to investigate the biochemical peculiarities of helminths. Ann Parasitol Hum Comp. 1990;65(SUPPL. 1):99–102. 10.      Yadav P, Singh R. A review on anthelmintic drugs and their future scope. Int J Pharm Pharm Sci. 2011;3(3):17–21. 11.      Holden-Dye L, Walker RJ. Anthelmintic drugs. WormBook. 2007;1–13. 12.     Salem HF, Kharshoum RM. Nanoprecipitation technique for preparation of sterically stabilized risperidone nano-suspension: In vitro and in vivo study. Int J Pharm Pharm Sci. 2016;8(5):136–42. 13.      Shariare MH, Altamimi MA, Marzan AL, Tabassum R, Jahan B, Reza HM, et al. In vitro dissolution and bioavailability study of furosemide nano-suspension prepared using design of experiment (DoE). Saudi Pharm J. 2019;27(1):96–105. 14.      Agrawal Y, Patel V. Nano-suspension: An approach to enhance the solubility of drugs. J Adv Pharm Technol Res. 2011;2(2):81. 15.      Rao Y, Kumar M, Apte S. Formulation of Nano-suspensions of Albendazole for Oral Administration. Curr Nanosci. 2008;4(1):53–8. 16.      Zhang J, Xie Z, Zhang N, Zhong J. Nano-suspension drug delivery system: preparation, characterization, postproduction processing, dosage form, and application [Internet]. Nanostructures for Drug Delivery. Elsevier Inc.; 2017. 413–443 p. Available from: http://dx.doi.org/10.1016/B978-0-323-46143-6/00013-0 17.      Patel AA, Patel RJ, Mishra P. Nano-suspension for oral delivery of tadalafil: Pharmacodynamic and pharmacokinetic studies. J Drug Deliv Sci Technol [Internet]. 2021;61(October):102203. Available from: https://doi.org/10.1016/j.jddst.2020.102203 18.      Nixon SA, Welz C, Woods DJ, Costa-Junior L, Zamanian M, Martin RJ. Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics. Int J Parasitol Drugs Drug Resist. 2020;14(July):8–16. 19.      Gundamaraju R. Evaluation of anti-helminthic activity of Ferula foetida “ Hing- A natural Indian spice” aqueous extract. Asian Pacific J Trop Dis. 2013;3(3):189–91.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareTooth Loss and its Association with the Number of Children and Interpregnancy Interval: A Cross-Sectional Study Among Yemeni Women English5158Anas ShamalaEnglish Ebtesam Al-MaimooniEnglish Salsbeel Al-MatariEnglish Ryhana HiyatEnglish Mohammed Ali Al-wesabiEnglish Sadeq Ali Al-MaweriEnglish Mohammad Zakaria NassaniEnglish Esam HalboubEnglishIntroduction: Physiological pregnancy changes can negatively impact the oral health of pregnant women. Objectives: The present study sought to assess tooth loss among a sample of Yemeni women in association with the number of children and interpregnancy interval. Subjects and Methods: This cross-sectional study was conducted on 644 Yemeni women. The subjects were interviewed to collect relevant socio-demographic factors, including age, education, and number of children. Oral hygiene practices as well as oral habits (such as qat chewing and smoking) were also recorded. Number of missing teeth was ascertained through clinical examination. Results: Around 644 women aged between 16 and 51 years participated in the study. Overall, the participants revealed poor oral hygiene practices, with only one-fifth of the sample reported brushing their teeth regularly (i.e., at least once a day), and around 36.8% reported using dental aids occasionally. Some 52% and 21% of the sample were qat chewers and smokers, respectively. The mean number of tooth loss and the number of children were 4.7 and 4.15, respectively; approximately 54% of the participating women had more than 3 children. The logistic regression revealed a significant association between the number of children and tooth loss. Conclusion: Yemeni women showed unsatisfactory oral hygiene practices and a high prevalence of tooth loss which increased proportionally with the number of children and interpregnancy interval. This emphasizes the importance of effective oral hygiene motivation and health education among females during pregnancy periods. EnglishGiving birth pregnant, Interpregnancy interval, Oral hygiene, Tooth loss, Qat chewing, YemenIntroduction Dental diseases are amongst the most prevalent health issues worldwide. 1[A1]  In particular, the tooth loss is a significant health burden that gravely impacts the patients’ quality of life. 2 Tooth loss is considered a marker of both periodontal disease and dental caries, though teeth can be lost due to other reasons such as trauma. 3 The former, periodontal disease, is a very common chronic condition affecting a considerable proportion of the adult population worldwide. 4 It is characterized by progressive inflammatory destruction of tooth-supporting structures in response to dental biofilm. 5,6 If untreated, periodontal disease may progress, destroying soft and hard tissues surrounding the tooth, causing attachment loss, tooth mobility and eventually tooth loss and edentulism. 4,7 The current evidence suggests that periodontal disease/tooth loss is a risk factor for several systemic diseases such as rheumatoid arthritis, atherosclerosis, respiratory diseases and non-alcoholic fatty liver disease. 8-12 it is recognized that dental plaque (biofilm) is the main causative agent for periodontal diseases. 6 However, a plethora of factors including poor oral hygiene, tobacco use, alcohol consumption, advanced age, low socioeconomic status, stress, and systemic conditions such as diabetes mellitus, obesity, and osteoporosis, and pregnancy have been reported to increase the risk and severity of periodontitis. 13-18 Pregnancy, a physiological phenomenon, has been reported as a risk factor for oral diseases including periodontitis. 19-22 It is associated with several hormonal changes that alter the gingival response to dental plaque, thus increasing its susceptibility to gingival inflammation and periodontal diseases. 20,22,23 Several studies have reported greater gingival inflammation during pregnancy. 19,21,22 and other studies reported a positive association between number of giving births and tooth loss. 24-26 In Yemen, the prevalence of dental diseases such as periodontitis, dental caries and tooth loss is amongst the highest in the world 16,27,28. This might be ascribed to the poor socioeconomic status, high prevalence of tobacco use and chewing habits, and limited human resources. 16,29-31 By and large, studies on oral health in Yemen -especially among women- are very limited, and most of these studies were conducted among males, mainly in relation to local oral habits, namely smokeless [A2] tobacco and qat chewing. 16,27,28,31,32 However, no any attempt has been made to assess the relationship between frequency of pregnancy and oral health outcomes among Yemeni women. Availability of such information is very important for planning public health prevention and promotion programs. Hence, the present study sought to: 1) assess oral health status (using tooth loss as a proxy indicator) of Yemeni women, and 2) determine the prevalence and relationship between tooth loss and number of children and interpregnancy interval among Yemeni women who attended the dental clinics, College of Dentistry, UST, Sana'a, Yemen. Subjects and Methods:             This study was of an observational cross-sectional design. The study protocol was reviewed and approved by the research ethical committee at the University of Science and Technology (UST), Sanaa, Yemen (No: EAC/UST179). The target population was women who attended the dental clinics, College of Dentistry, UST, Sana'a, (private university) Yemen. The study was conducted during the 2018-2019 academic year: from November 2018 to April 2019. The sample size was calculated using version 3.01 of OpenEpi software for epidemiologic statistics (Bill and Melinda Gates Foundation, Emory University, Atlanta, Georgia, USA); the required sample size for 95% confidence level and power of 80%,  was 424 subjects with minimally.             Women were included if they aged above 16 years and had a previous history of pregnancy. Women who were medically compromised or were out of the said age range were excluded. The participants were informed about the study aims and procedures and asked to provide their consent to participate anonymously. The participant’s sheet comprised questions related to age, education, qat chewing, smoking, oral hygiene practices, oral hygiene aids, previously periodontal treatments and dental and medical history.  The sheet included also items about the frequency of pregnancy along with the number of children as to take into account for the chance of premature birth and the Interpregnancy interval period. The study was based on the following criteria:  Frequency of pregnancy: The number of women who became pregnant throughout their life, regardless of the outcome. Also excluding premature births, we add the number of children as an independent variable as dichotomous 3 children. Interpregnancy interval period is defined as the length of time between the events of multiple pregnancy as 4 years. The number of missing teeth was presented as a mean and standard deviation,  for statistical issues, its then categorized into three categories (10 teeth ). For the purpose of performing binary logistic regression analysis the “missing teeth” was further transformed to a dichotomous variable ("Three or less missed teeth" and "More than three teeth missed"). Third molars or teeth missing congenitally or due to previous orthodontic or traumatic treatment.  The number of missing teeth evaluated by two well-trained dentists using a sterile dental examination kit under the artificial light of the dental chair. Intra- and inter-examiner agreements were conducted on fifty cases in two different occasions with a week interval. Kappa statistic revealed a perfect intra-examiner agreement (1) and a high level of inter-examiner reliability (0.9).             The analysis of the collected data was carried out using the SPSS statistical package (IBM SPSS Statistics for Windows, Version 20.0, Released 2011, IBM Corp, Armonk, New York, USA). The demographics and other characteristics of study population were presented as frequency with proportion and mean with standard deviation, as appropriate. The bivariate analyses were done using independent t-test or ANOVA to identify any potential differences in the mean number of missing teeth between two or more different subgroups, respectively. Spearman’s correlation analysis was applied in order to identify any correlations between number of “missing teeth” and the number of children and interpregnancy interval. The outcome variable was “number of missing teeth”, and level of education, oral health practices including frequency of tooth brushing and using oral hygiene aids, gum bleeding, periodontal treatment, number of children, interval between pregnancy were considered as independent variables (determinants) and it added to the model using “enter” method. Odd ratios (ORs) and their 95% confidence intervals (CIs) were calculated, and the significance level was set at PEnglishhttp://ijcrr.com/abstract.php?article_id=4409http://ijcrr.com/article_html.php?did=44091. Righolt A, Jevdjevic M, Marcenes W, Listl S. Global-, regional-, and country-level economic impacts of dental diseases in 2015. Journal of Dental Research. 2018;97(5):501-7. 2. Schierz O, Baba K, Fueki K. Functional Oral Health?Related Quality of Life Impact: A Systematic Review in Populations with Tooth Loss. J. Oral Rehabil. 2020. 3. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. The lancet. 2005;366(9499):1809-20. 4. Papapanou PN, Susin C. Periodontitis epidemiology: is periodontitis under-recognized, over-diagnosed, or both Periodontology 2000. 2017;75(1):45-51. 5. Murakami S, Mealey BL, Mariotti A, Chapple IL. Dental plaque–induced gingival conditions. Journal of clinical periodontology. 2018;45:S17-S27. 6. Curtis MA, Diaz PI, Van Dyke TE. The role of the microbiota in periodontal disease. Periodontology 2000. 2020;83(1):14-25. 7. Meyle J, Chapple I. Molecular aspects of the pathogenesis of periodontitis. Periodontology 2000. 2015;69(1):7-17. 8. Beukers NG, van der Heijden GJ, van Wijk AJ, Loos BG. Periodontitis is an independent risk indicator for atherosclerotic cardiovascular diseases among 60 174 participants in a large dental school in the Netherlands. J Epidemiol Community Health. 2017;71(1):37-42. 9. de Oliveira Ferreira R, de Brito Silva R, Magno MB, Carvalho Almeida APCPS, Fagundes NCF, Maia LC, et al. Does periodontitis represent a risk factor for rheumatoid arthritis? A systematic review and meta-analysis. Therapeutic advances in musculoskeletal disease. 2019;11:1759720X19858514. 10. Moghadam SA, Shirazaiy M, Risbaf S. The associations between periodontitis and respiratory disease. J. Nepal Health Res. Counc.. 2017;15(1):1-6. 11. Alakhali MS, Al-Maweri SA, Al-Shamiri HM, Al-haddad K, Halboub E. The potential association between periodontitis and non-alcoholic fatty liver disease: A systematic review. Clinical oral investigations. 2018;22(9):2965-74. 12. Bui FQ, Almeida-da-Silva CLC, Huynh B, Trinh A, Liu J, Woodward J, et al. Association between periodontal pathogens and systemic disease. biomedical journal. 2019. 13. Moeintaghavi A, Arab HR, Rezaee SAR, Naderi H, Shiezadeh F, Sadeghi S, et al. The effects of smoking on expression of IL-12 and IL-1β in gingival tissues of patients with chronic periodontitis. The open dentistry journal. 2017;11:595. 14. Jaiswal R, Shenoy N, Thomas B. Evaluation of association between psychological stress and serum cortisol levels in patients with chronic periodontitis-Estimation of relationship between psychological stress and periodontal status. J. Indian Soc. Periodontol. 2016;20(4):381. 15. Shamala A, Al-Hajri M, Al-Wesabi A. Risk factors for periodontal diseases among Yemeni type II diabetic patients. A case-control study. Journal of Oral Research. 2017;6(7):176-81. 16. Al-Hajj W, Hwaiti H, Shamala A, Al-Azazi H, Alwesabi M. Association of Khat chewing, smoking, age and sex with periodontal status among Yemeni adults. Brazilian Dental Science. 2020;23(1):8. 17. Kalakonda B, Al-Maweri S-A, Al-Shamiri H-M, Ijaz A, Gamal S, Dhaifullah E. Is Khat (Catha edulis) chewing a risk factor for periodontal diseases? A systematic review. J. clin. exp. dent.. 2017;9(10):e1264. 18. Dhaifullah E, Al-Maweri SA, Koppolu P, Elkhtat E, Mostafa D, Mahgoub M. Body mass index and periodontal health status among young Saudi adults: a cross-sectional study. Annals of Saudi Medicine. 2019;39(6):433-40. 19. Adesina KT, Ernest MA, Tobin AO, Isiaka-Lawal SA, Adeyemi MF, Olarinoye AO, et al. Oral health status of pregnant women in Ilorin, Nigeria. J Obstet Gynaecol. 2018;38(8):1093-8. 20. Laine MA. Effect of pregnancy on periodontal and dental health. Acta Odontologica Scandinavica. 2002;60(5):257-64. 21. Wandera M, Engebretsen IM, Okullo I, Tumwine JK, Åstrøm AN, Group P-eS. Socio-demographic factors related to periodontal status and tooth loss of pregnant women in Mbale district, Uganda. BMC Oral Health. 2009;9(1):18. 22. Boggess KA. Pathogenicity of periodontal pathogens during pregnancy. Am. J. Obstet. Gynecol.. 2005;193(2):311-2. 23. Balan P, Chong YS, Umashankar S, Swarup S, Loke WM, Lopez V, et al. Keystone species in pregnancy gingivitis: a snapshot of oral microbiome during pregnancy and postpartum period. Frontiers in microbiology. 2018;9:2360. 24. Cozier YC, Heaton B, Bethea TN, Freudenheim JL, Garcia RI, Rosenberg L. Predictors of self-reported oral health in the Black Women's Health Study. J. Public Health Dent. 2020;80(1):70-8. 25. Han K, Kim I, Park Y-G, Park J-B. Associations between the number of natural teeth and the maternal age at childbirth or history of parity in postmenopausal women: the 2010–2012 Korea national health and nutrition examination survey. Advances in Clinical and Experimental Medicine. 2017;26(4):627-33. 26. Ueno M, Ohara S, Inoue M, Tsugane S, Kawaguchi Y. Association between parity and dentition status among Japanese women: Japan public health center-based oral health study. BMC public health. 2013;13(1):993. 27. Amran AG, Alhajj MN, Amran AN. Prevalence and Risk Factors for Clinical Attachment Loss in Adult Yemenis: A Community-Based Study in the City of Dhamar. Am. J. Health Res. 2016;4(3):56-61. 28. Al Alimi A, Halboub E, Al?Sharabi AK, Taiyeb?Ali T, Jaafar N, Al?Hebshi NN. Independent determinants of periodontitis in Yemeni adults: A case?control study. International journal of dental hygiene. 2018;16(4):503-11. 29. Dhaifullah E, Al-Maweri SA, Al-Motareb F, Halboub E, Elkhatat E, Baroudi K, et al. Periodontal health condition and associated factors among university students, Yemen. Journal of clinical and diagnostic research: JCDR. 2015;9(12):ZC30. 30. Al-Sharabi AK, Shuga-Aldin H, Ghandour I, Al-Hebshi NNJ. Qat chewing as an independent risk factor for periodontitis: a cross-sectional study. Int. J. Dent. 2013;2013. 31. Sadeq-Ali A-M, AlAkhali M. Oral hygiene and periodontal health status among khat chewers. A case-control study. J. clin. exp. dent. 2017;9(5):e629. 32. Al-Maweri SA, Alaizari NA, Al-Sufyani GA. Oral mucosal lesions and their association with tobacco use and qat chewing among Yemeni dental patients. J. clin. exp. dent.. 2014;6(5):e460. 33. Markou E, Eleana B, Lazaros T, Antonios K. The influence of sex steroid hormones on gingiva of women. The open dentistry journal. 2009;3:114. 34. Russell SL, Ickovics JR, Yaffee RA. Exploring potential pathways between parity and tooth loss among American women. Am. J. Public Health. 2008;98(7):1263-70. 35. Wandera MN, Engebretsen IM, Rwenyonyi CM, Tumwine J, Åstrøm AN, Group P-ES. Periodontal status, tooth loss and self-reported periodontal problems effects on oral impacts on daily performances, OIDP, in pregnant women in Uganda: a cross-sectional study. Health and quality of life outcomes. 2009;7(1):89. 36. Lu H-X, Xu W, Wong MCM, Wei T-Y, Feng X-P. Impact of periodontal conditions on the quality of life of pregnant women: a cross-sectional study. Health and quality of life outcomes. 2015;13(1):67. 37. Christensen K, Gaist D, Jeune B, Vaupel JW. A tooth per child? The Lancet. 1998;352(9137):1387. 38. Al Maweri SA, Warnakulasuriya S, Samran A. Khat (Catha edulis) and its oral health effects: An updated review. J Investig Clin Dent. 2018;9(1):e12288. 39. Halboub E, Dhaifullah E, Abdulhuq M. Khat chewing and smoking effect on oral mucosa: a clinical study. Acta Medica (Hradec Kralove). 2009;52(4):155-8. 40. Al-Maweri SA, Al-Jamaei AA, Al-Sufyani GA, Tarakji B, Shugaa-Addin B. Oral mucosal lesions in elderly dental patients in Sana’a, Yemen. J Int Soc Prev Community Dent. 2015;5(Suppl 1):S12. 41. Almashraqi AA, Halboub ES, AlMaweri SA, Barngkgei I, Alwesabi MA, Alkamel A, et al. Cone beam computed tomography findings in the temporomandibular joint of chronic qat chewers: Dimensional and osteoarthritic changes. J. Oral Rehabil. 2020. 42.  Amran AG, Alhajj MN. Assessment of Gingival Health Status among a Group of Preclinical and Clinical Dental Students at Thamar University, Yemen. 43. AlMaweri SA, Al?Jamaei A, Saini R, Laronde DM, Sharhan A. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareFrequency of Hyperkalemia in Patients with Paraphenylenediamine Poisoning at a Tertiary Care Hospital English5963Abdul Malik MujahidEnglish Asma Binte SaadEnglish Mahriq FatimaEnglish Hassan ShabirEnglish Muhammad Umer FarooqEnglish Shohreh AhmadiEnglishIntroduction: Paraphenylenediamine is a low-cost and readily available hair dye in Pakistan. It is highly toxic and lethal substance when ingested. This study was conducted to determine the frequency of hyperkalemia in patients with PPD poisoning. Objective: To determine the frequency of hyperkalemia in patients with PPD-poisoning at a tertiary care hospital. Material and Methods: A descriptive case series study was conducted at Teaching Hospital Dera Ghazi Khan, from 1st January, 2019 to 30th June, 2020. A total of 87 patients fulfilling the inclusion criteria were enrolled. After the approval from hospital ethical Committee, informed consent was obtained from all the patients. Once registered, 3 ml venous blood sample was drawn and sent to the hospital laboratory (after every 12 hours) for serum potassium levels to diagnose hyperkalemia. Data was entered and analyzed using SPSS-23. Results: Out of 87 cases, 20 (23.0 %) were male while 67 (77.0 %) were female patients. Mean age was25.69 ± 7.43 years with age range of 18-45 years. 65 patients (74.7 %) belonged to rural areas and 22 (25.3 %) to urban areas. Poor socioeconomic status was noted in 71 (81.6%) while 16 (18.4%) were of middle income. Out of 87 cases, 52 (58.9%) were illiterate and 35 (40.2%) were literate. Reason for intake was homicidal in 22 (25.3%) and suicidal in 65 (74.7%). Mean hospital stay was 6.23 ± 3.39 days and 54 (62.1 %) had hospital stay for more than 3 days. Mean serum potassium level was 5.10 ± 0.45 mmol/L and hyperkalemia was noted in 23cases (26.4%). Conclusion: High frequency of hyperkalemia was noted in our study among patients with Paraphenylenediamine poisoning and resulted in prolong duration of hospitalization. EnglishParaphenylenediamine poisoning, Hyperkalemia, Serum Potassium, Tertiary care Hospital, Hair dye, SuicidalINTRODUCTION: Poisoning is one of the common ways of suicide and deliberate self-harm.1 In underdeveloped countries including Pakistan where poverty is common due to unemployment and the literacy rate is low, use of Paraphenylenediamine has become a common method of poisoning as it is readily available and cheap in the market. PPD ingestion causes different signs and symptoms due to the involvement of multiple organs. It is brown or black-colored solid substance, a derivative of para-phenylaniline and easily soluble in H2O2.2,3,4 PPD is metabolized by electron oxidation with cytochrome P450 peroxidase to form a reactive compound called benzoquinone diamine. This can be further oxidized to a substance known as Brandowaski's base, reported causing anaphylaxis. The first case of PPD poisoning was reported in 19245 when a barber accidentally developed toxicity while handling the dye. Hair Dye Poisoning is highly uncommon in developed countries due to strict formulary regulations; however, in developing world like Asia and Africa, it is emerging as a common means of suicide. In southeast Asia especially in India, use of hair dye as a suicidal tool is reported to have a mortality rate reaching up to 24 percent even with treatment4. As there is no antidote available for PPD poisoning, only early recognition of symptoms and timely management is the key treatment option to avoid adverse effects. Paraphenylenediamine is a major toxic substance in hair dye which can cause life-threatening neck and facial edema, laryngeal edema that may need emergency tracheostomy or endotracheal intubation to secure airway and muscle damage that may cause rhabdomyolysis and lead to acute renal failure.6 PPD poisoning is associated with a significant increase in morbidities and mortalities and is more common in females as compared to males and is more prevalent in lower social classes. In Pakistan, most incidents are reported from Sindh and Punjab related to hair dye poisoning.7, 8 Hair dye powder is readily available and its excessive use in this area has led to clinical implications of its toxicity that may accidental or suicidal. A study conducted by Haider et al.,9 has reported 34.4 % hyperkalemia in patients presenting with PPD poisoning. This study has been proposed to document hyperkalemia in patients with PPD poisoning as we commonly treat such patients in our daily practice but no such study has been done in our local population (Dera Ghazi Khan). The results of this study will generate baseline database of our local population and help clinicians to anticipate such adverse events in early stages which will lead to the proper management of such cases. OBJECTIVE: To determine the frequency of hyperkalemia in patients with PPD-poisoning at a tertiary care hospital MATERIAL AND METHODS: A descriptive case series study was conducted at the Department of Medicine, Teaching Hospital Dera Ghazi Khan from 1st January, 2019 to 30th June, 2020. A total of 87 cases were enrolled through a non-probability, consecutive sampling. All the patients with PPD poisoning with either gender; between 15 – 60 years were included and patients with past history of kidney and chronic liver disease were excluded. After the approval from hospital ethical review committee (NO.7925/Teach: Hosp: D.G.Khan/ Dated 16/12/2018), informed consent was taken for each patient. A pre-designed proforma (ANNEXURE-1) was used to collect information regarding reason for intake (suicidal, homicidal, accidental), level of education, location (urban, rural), duration of hospital stay, gender, age and family income. Once registered, 3 ml venous blood sample was drawn and sent to the hospital laboratory (after every 12 hours) for serum potassium levels to diagnose hyperkalemia. Data was entered and analyzed by a consultant physician with 10 year of post-fellowship experience using SPSS-23. Descriptive statistics was applied to calculate mean and standard deviation for the age, hospital stay and Serum potassium level. Frequencies and percentages were calculated for categorical variables like gender, age groups, reason for intake, residential status, family income, level of education and hyperkalemia. Effect modifiers like age, residential status, family income, level of education, duration of hospital stay, gender and reason for intake were controlled by stratification. Post stratification chi-square test was applied to see their effect on hyperkalemia. P-value equal or less than 0.05 was considered as significant.  RESULTS:  A total of 87 patients were included in study. Out of these, 20 (23.0 %) were male patients while 67 (77.0 %) were female patients. Mean age was 25.69 ± 7.43 years with age range in 18-45years. Majority of our study cases i.e. 74 (85.1 %) were aged up to 35 years. Out of these 87 cases, 65 (74.7 %) belonged to rural areas and 22 (25.3 %) belonged to urban areas. Poor socioeconomic status was noted in 71 (81.6%) while 16 (18.4%) were of middle income. 52 patients (58.9%) were illiterate and 35 (40.2%) were literate. Reason for intake was homicidal in 22 (25.3%) and suicidal in 65 (74.7%).  Mean hospital stay of our study cases was 6.23 ± 3.39 days and 54 (62.1 %) had hospital stay for more than 3 days. Mean serum potassium level was 5.10 ± 0.45 mmol/L and hyperkalemia was noted in 23 (26.4%) (Table No.1). Hyperkalemia was stratified with regards to gender, age, residential status, socioeconomic status, literacy, reason for intake and hospital stay. Length of hospital stay showed a significant relationship with hyperkalemia (Table No. 2) DISCUSSION: A poison is chemical agent that produces adverse effects when enter the human body. Intoxication by hair dye is very common in Pakistan and this is usually attributed to the active ingredient Paraphenylenediamine (PPD). Some other hair dyes exist where the active ingredient is different from PPD e.g. NTD and other aromatic amine compounds. Intoxication can be either topical or oral or inhalational route. Cutaneous absorption and ingestion produce sever local reactions and systemic effects. There were significant biochemical and histopathological changes noted in cases admitted to the hospital. Death may occur following ingestion or absorption of small amount although the lethal dose reported in the literature is ten gram. The usual patterns of intoxication are Suicidal about (84percent), Accidental especially in children due to ingestion (eight %), Homicidal about (6percent) or through skin absorption when used for cosmetic purpose (two %). In mild cases, allergic reaction caused by use of hair dye usually involves the upper eyelids and ear, while in more advance cases there may be complete closure of eyelids and allergic contact dermatitis reaction may become widespread 10. In our study, 20 (23.0 %) were male patients while 67 (77.0 %) were female patients. Similar results have been reported in many different studies showing PPD ingestion being more common in young female population. A study conducted by Tanweer et al.11 has reported around 78 percent female gender predominance and the study by Elgamel et al.10 has also reported about 80percent females in PPD Poisoning which is comparable with our study results. A study conducted by Ishtiaq et al.12 has also reported that seventy-one % females were involved in this poisoning. A study conducted by Kondle et al.13 has also reported eighty-two percent female gender involved. Another study by Sakuntala et al.14 and Khan et al.15 has reported about 81 percent and sixty five percent female preponderance respectively which are in compliance with our study results. Mean age of our study cases was 25.69 ± 7.43 years with age range of 18-45 years. The majority of our study cases i.e. 74 (85.1 %) were aged up to 35 years. A study conducted by Tanweer et al.11 reported 23.21 ± 8.2 years mean age of the patients which is close to our study results. A study conducted by Ishtiaq et al.12 and Kondle et al.13 has also reported mean age 22 ± 3.4 years and 23.8 ± 7.8 years respectively and Khanet al.15 has also reported 21 years mean age, similar to that of our study results. Out of 87 study cases, 65 (74.7 %) belonged to rural areas and 22 (25.3 %) to urban areas. Poor socioeconomic status was noted in 71 (81.6%) while 16 (18.4%) were of middle income. A study conducted by Ishtiaq et al.12 has reported 72 percent of patients from lower socioeconomic status and 74 percent from rural areas which are comparable with our study results. Another study by Khan et al.15 has also reported sixty-five % PPD poisoning cases belonged to poor families and 64.30 percent were illiterate. Reason for intake was homicidal in 22 (25.3%) and suicidal in 65 (74.7%). A study conducted by Tanweer et al.11 has also reported 82 percent suicidal intentions which is close to our study results. The mean hospital stay of our study cases was 6.23 ± 3.39 days and 54 (62.1 %) had a hospital stay for more than 3 days. A study conducted by Tanweer et al.11 has also reported 9.5 day mean duration of hospitalization which is in compliance with our study results. The mean serum potassium level was 5.10 ± 0.45 mmol/L and hyperkalemia was noted in 23 (26.4%). A study conducted by Haider et al.9 has reported 34.4 % hyperkalemia in patients presenting with PPD poisoning. CONCLUSION: A high frequency of hyperkalemia was noted in our study among patients with Paraphenylenediamine poisoning and resulted in a prolonged duration of hospitalization. There is a dire need for proper legislation and implementation of law enforcement regarding the readily availability of the PPD on the counter for its control and prevention as it is associated with a significant increase in adverse events after ingestion. Acknowledgment The authors acknowledge the immense help received from the scholars whose articles are cited and included in the references of this manuscript Source of Funding None Conflict of interest None Authors Contribution Dr. Abdul Malik Mujahid. Principal contributor, conceptualization, and design of research work, final approval Dr. Asma Binte Saad Writing of manuscript, collection of data Dr. Mahriq Fatima Literature search, statistical analysis Dr. Hassan Shabir Co contributor, data collection, drafting Dr. Muhammad Umer Farooq Data analysis, plagiarism correction, literature search Dr. Shohreh Ahmadi Result analysis, review of the manuscript Englishhttp://ijcrr.com/abstract.php?article_id=4410http://ijcrr.com/article_html.php?did=4410 Shah MMA, Ahmed S, Arafat SMY. Demography and risk factors of suicide in Bangladesh: a six-month paper content analysis. Psy J. 2017; 2017:3047025. Sakuntala P, Khan PM, Sudarsi B, Manohar S, Siddeswari R, Swaroop K. Clinical profile and complications of hair dye poisoning. Int J Sci Res Pub. 2015;5(6):1–4. Khan N, Khan H, Khan N, Ahmad A, Shah F, Rahman AU et al. Clinical presentation and outcome of patients with paraphenylenediamine (kala-pathar) poisoning. Gomal J Med Sci. 2015; 14(1):3–6. Kondle R, Pathapati RM, Saginela SK, Malliboina S, Makineedi VP. Clinical profile and outcomes of hair dye poisoning in a teaching hospital in Nellore. ISRN Emerg Med. 2012; 624253:5. Nott HW. Systemic poisoning by hair dye. Br Med J. 1924;1(3297):421–2. 78 Umair SF, Amin I, Urrehman A. Hair Dye poisoning: "An early intervention". Pak J Med Sci. 2018 Jan-Feb; 34(1):230-32. Naqvi R, Akhtar F, Farooq U, Ashraf S, Rizvi SA. From diamonds to black stone; myth to reality: Acute kidney injury with Paraphenylenediamine poisoning. Neph J.2015;20(12):887–91. Bokutz M, Nasir N, Mahmood F, Sajid S. Hair dye poisoning and rhabdomyolysis. J Pak Med Assoc. 2015;65(4):425–26 Haider SH, Sultan A, Salman Z, Waris S, Bandesha Y. Paraphenylenediamine poisoning: clinical presentations and outcomes. Anaesth Pain Inten Care. 2018;22(1):43-7. Elgamel AA, Ahmed NO. Complications and management of hair dye poisoning in Khartoum. Sudan Med Monit 2013;8:146-52 Tanweer S, Saeed M, Zaidi S, Aslam W. Clinical Profile and Outcome of Paraphenylenediamine Poisoning. J Coll Phy Surg Pak. 2018;28(5):374-77. Ishtiaq R, Shafiq S, Imran A, Masroor Ali Q, Khan R, Tariq H, et al. Frequency of Acute Hepatitis Following Acute Paraphenylene Diamine Intoxication. Cureus. 2017 Apr 21;9(4):e1186. Kondle R, Phatapati RM, Saginela SK, Malliboina S, Makineedi VP. Clinical profile and outcome of hair dye poisoning in a teaching hospital in Nellore. ISRN Emerg Med. 2012; 6 (2):42-53. Sakuntala P, Khan PM, Sudarsi B, Manohar S, Siddeswari R, Swaroop K. Clinical profile and complications of hair dye poisoning. Int J Sci Res Pub. 2015;5(6):1-4. Khan MA, Akram S, Shah HBU, Hamdani SAM, Khan M. Epidemic of Kala Pathar (Paraphenylene Diamine) Poisoning: an Emerging Threat in Southern Punjab. J Coll Phy Surg Pak. 2018;28(1):44-7. 

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareA Comparative Study of the Effectiveness of Anticonvulscants in the Treatment of Tinnitus English6470Anagha RajguruEnglish Kaenat AhmedEnglish Yarlagadda Lakshmi SravyaEnglish Samiksha KarnaEnglishIntroduction: Tinnitus has defined perception of an audiological sensory impulse in the absence of any external force. There are various causes considered for the pathophysiology of tinnitus but none are established. Carbamazepine is a commonly used anti-epileptic drug that functions by depressing the CNS response to excitatory stimuli. Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter throughout the central nervous system and is also expressed in the inner ear. Piracetam is a commonly used anti-epileptic that is known to increase cerebral blood flow and perfusion. Methods: A group of 80 patients were evaluated by taking a detailed history and a subjective assessment of the tinnitus using Tinnitus Handicap Inventory Questionnaire. The patients were followed up for 3 months and were assessed with Pure Tone Audiometry both pre and post treatment to evaluate which drug is better. The patients were randomized into 3 groups and one control group. Each group consisted of 20 patients. Results: The study consisted of 46 males and 34 females. A significant difference was seen when the results of group A and C were compared with p-value 0.00512, 0.00512 and 0.0083 and U value 0, 0 and 1 showing improvement from severe to moderate, moderate to mild and mild to normal. A comparison of group A and D showed a significant change from severe to moderate, moderate to mild and mild to normal with p-value 0.00512, 0.00512 and 0.0512 respectively and U values 0, 0 and 0 respectively. Conclusions: In our study, we concluded that use of Piracetam helps in reducing tinnitus and the treatment should continue as long it persists. Thus, Piracetam and Gabapentin are effective as a modality of treatment in suppressing tinnitus according to this study. We hope that our outcomes will be helpful for patients suffering from chronic tinnitus. EnglishTinnitus, Hearing loss, Antiepileptics, Gabapentin, Piracetam, VascularityINTRODUCTION: Tinnitus is defined perception of an audiological sensory impulse in the absence of any external force. It is considered to be a symptom rather than a disease and presents differently in each patient in characteristics and cause. There are various causes considered for the pathophysiology of tinnitus but none are established. Although it is most commonly associated with acoustic or cranial trauma, presbycusis, systemic or metabolic disorders, otological infections, arthritis, or pharmacological interactions, it may be present in patients without any other ear complaints.  It has a prevalence of about 10-25% and is seen in adults from all walks of life. Tinnitus can present variably in different patients. Some may perceive a low background humming while others may complain of loud disruptive noise interfering with day-to-day conversations. It is classified in two ways: subjective or objective. Subjective is the kind of sound that is audible to the patient only, while the objective is when the examiner too can hear the sound. It is usually due to vascular causes such as AV malformations or glomus jugulare. A simple examination by listening through a stethoscope can help differentiate the two.  It is usually associated with some audiological impairment. Hearing loss associated with tinnitus may be conductive, sensory or central depending on the pathology causing the symptom. An audiogram in a patient complaining of tinnitus may thus be a useful investigation to help single out the cause. However, even in today’s day, there is no investigation or test that leads to the cause and hence the management of tinnitus.   Therefore, the primary area of effort has been to alleviate the symptoms and improve the quality of life. Tinnitus retraining therapy is a habituation-based therapy in order to make the patient comfortable with the symptom and lead a productive life.  It is based on the idea that combining educational counseling and sound therapy to reduce the patient’s anxiety and uneasiness. 1 Carbamazepine is a commonly used anti-epileptic drug that functions by depressing the CNS response to excitatory stimuli. It acts by binding with voltage-gated sodium channels and stabilizes it in the inactive state. It, therefore, acts by reducing neural firing.3-6 Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter throughout the central nervous system and is also expressed in the inner ear. When GABA binds to the GABAA receptor, it opens the associated chloride (Cl–) channels and allows a flow of Cl– into the neuron. Thus, GABA hyperpolarizes the neuronal membrane and makes the cell less reactive to the excitatory neurotransmitters. Tinnitus has been hypothesized to be the result of spontaneous hyperactivity at one or multiple levels in the auditory pathway, and this means that a reduction in GABA levels could theoretically result in increased spontaneous activity in the auditory pathway and contribute to the sensation of tinnitus. Piracetam is a commonly used anti-epileptic that is known to increase cerebral blood flow and perfusion.7-9 Tinnitus is a symptom of pathology rather than a disease. There are various probable mechanisms of action that were studied over the years. (a) Abnormal afferent excitation at a cochlear level due to i) Mechanical tinnitus based on spontaneous otoacoustic emissions ii) Glutamate neurotoxicity iii) Enhanced sensitivity of NMDA and non-NMDA receptors iv) Abnormal ion channel conductance calcium channel dysfunction (b) Efferent dysfunction/reduction of GABA effect (c) Alteration of spontaneous activity and tonotopic reorganization. There are many treatment modalities that have been tried with varied results depending on the patients and the underlying pathologies. Antidepressants, GABA analogs, Calcium channel blockers, Prostaglandin blockers and ginkgo Biloba extracts are some of the medical treatments that have been tried. Surgical modalities such as cochlear destruction and the auditory nerve section have been tried with very little success. 10-11 There are no reliable means of curing tinnitus at its source. Current efforts thus aim to reduce the effect of tinnitus on health-related quality of life, with some evidence for the efficacy of cognitive-behavioral therapy. Tinnitus retraining therapy (TRT), an internationally recognized habituation-based treatment grounded in the neurophysiological model of tinnitus, also aims to reduce the effect of tinnitus on health-related quality of life. Tinnitus retraining therapy combines tinnitus-specific educational counseling (TC), synonymous with directive counseling, and low-level broadband sound therapy (ST) to habituate the patient to perceived tinnitus so as to lessen the patient's associated negative emotional reactions (eg, annoyance or anxiety) and improve the patient's quality of life.12 Materials and Methods This study was conducted between June 2020 and July 2021 on patients between the ages 20 years to 60 years of both sexes that presented with a history of chronic idiopathic tinnitus to Krishna Institute of Medical Science, Karad. A detailed history was taken and a subjective assessment of the tinnitus using the Tinnitus Handicap Inventory Questionnaire. Clinical examination, auditory assessment and imaging were done wherever appropriate. The patients were followed up for 3 months and were assessed with Tinnitus Handicap Inventory Questionnaire and Pure Tone Audiometry both pre and post-treatment to evaluate which drug is better. The patients were randomized into 3 groups and one control group. Group A consisted of patients that were given B complex capsules once a day. Group B patients were given tb Carbamazepine 200mg thrice a day. Group C patients were given Piracetam 800mg thrice a day. Group D patients were given Gabapentin 1800mg/ day divided into doses. Each group consisted of 20 patients. Thus 80 patients were studied in this study. Inclusion Criteria: 1. Minimum age 20 yrs 2. Tinnitus for a minimum of 6 months 3. Cochlear and retrocochlear pathology Exclusion Criteria: 1. Tinnitus due to systemic vascular or diabetic disease, anxiety, depression. 2. Tinnitus due to external and middle ear causes. 3. Meniere disease, Vestibular schwannoma or cerebellopontine angle tumors. RESULTS This study was conducted in the Out-Patient of the Department of ENT with 80 patients. The study consisted of 46 males and 34 females. The study group was divided into group A, B, C and D randomly. Each group had 20 members assigned randomly. Group A and D consisted of 12 males and 8 females and 11 males and 9 females in group B and group C respectively. All patients that were included were cases of idiopathic chronic tinnitus and were explained the premise of the study in detail. All patients were rated according to the tinnitus handicap inventory on the day of inclusion in the study. Group A consisted of 4(M-2, F-2) that had grade I and 3(M-2, F-1), 5(M-3, F-2), 4(M-2, F-2) and 4 (M-3, F-1) scoring grade II, III, IV and V respectively. Group B consisted of 9(M-5, F-4) that had grade I and 3(M-2, F-1), 4(M-2, F-2), 2(M-1, F-1) and 2 (M-1, F-1) scoring grade II, III, IV and V respectively. There were 3 patients with grade I and II and 6 patients with grade III, 4 patients with grade IV and V in group C. There were 3 patients with grade I, 7, 4, 4 and 2 with grade II, III, IV and V respectively in group D. All patients also underwent pure tone audiometry to record any hearing loss if present. Group A had 3 patients with normal hearing, 3 with 26-40db hearing loss, 6 with 41-55db hearing loss, 4 with 56-70 db hearing loss, 3 with 71-90 db hearing loss and 1 with >90 db hearing loss. Group B had 4, 1, 4, 4, 3 and 3 with normal, 26-40 db hearing loss, 41-55 db hearing loss, 56-70 db hearing loss, 71-90 db hearing loss and > 90 db hearing loss respectively. Group C had 4, 5, 4, 2, 3 and 2 with normal, 26-40 db hearing loss, 41-55 db hearing loss, 56-70 db hearing loss, 71-90 db hearing loss and > 90 db hearing loss respectively. Group D had 4, 3, 3, 4, 3 and 3 with normal, 26-40 db hearing loss, 41-55 db hearing loss, 56-70 db hearing loss, 71-90 db hearing loss and > 90 db hearing loss respectively.  In all there were 18.75 % patients with normal hearing, 16.25%, 21.25%, 17.50%, 15.00% and 11.25% with 26-40db hearing loss, 41-55 db hearing loss, 56-70 db hearing loss, 71-90 db hearing loss and > 90 db hearing loss respectively. THI score was recorded over a span of 12 weeks and the results were compared as explained in the tables seen below. The results were compared using software SPSS 22.0 and the results were analysed and explained in table stated below. A significant difference was seen when the results of group A and C were compared with p-value 0.00512, 0.00512 and 0.0083 and U value 0, 0 and 1 showing improvement from severe to moderate, moderate to mild and mild to normal.  A comparison of group A and D showed a significant change from severe to moderate, moderate to mild and mild to normal with p value 0.00512, 0.00512 and 0.0512 respectively and U values 0, 0 and 0 respectively.  DISCUSSION: Tinnitus is an abnormal perception of sound without an external mechanical or electrical stimulant. Tinnitus is one of the frequent otological complaints reflecting an abnormality in perception which may be subjective or objective. There are local and systemic factors causing tinnitus. Among three-quarters of persons with tinnitus, the main cause is unknown (idiopathic). This study was done to ascertain the percentage of patients who had relief or reduction of symptoms by using Piracetam, Carbamazepine and Gabapentin and to compare whether Piracetam, Carbamazepine or Gabapentin is better in reducing tinnitus in a selected placebo-controlled group of patients. We studied a series of 80 patients with chronic tinnitus over a period of 2 years at the department of ENT, KIMS, Karad. The first study group comprised of 20 patients and was administered with Placebo which consisted of B complex tablets once daily for three months. It was considered the control group. Group B was administered Carbamazepine 200mg thrice daily for 3 months. Group C comprising of 20 patients was administered Piracetam 800mg thrice daily for 3 months.  And group D was administered with 600mg of gabapentin three times a day for 3 months. The results were recorded and studied extensively to draw conclusions. All four groups were matched by the distribution of age, sex and duration of tinnitus. In our study maximum numbers of patients were seen in the age group of 71- 80 years and 61-70 years with a mean 57.2 years and standard deviation of 15.656. This is comparable to a study by Scherer et al. in 2019. (1) The treatment pure tone audiogram findings were compared before and after and the results were compared. The patients were also compared on the basis of their response to the THI. A specific comparison was done to compare the response of the drugs in group A with group B, C and D. A significant difference was seen between group A and C and A and D with p values 0.00512, 0.00512 and 0.0083 and 0.00512, 0.00512 and 0.0512 respectively. This is in congruence with a study by Simha et al. (13) and Aazh et al. (2) Similarly there was a significant improvement in hearing in those patients who had sensorineural hearing loss when treated with Piracetam. Those patients treated with Carbamazepine also showed a reduction in post-treatment THI score, but it was not statistically significant. Gabapentin is an effective modality of treatment of tinnitus showing significant improvement in the group of patients with sever to moderate hearing loss.  Thus, in our study we concluded that use of Piracetam helps in reducing tinnitus and also improves sensorineural hearing loss in patients with tinnitus and the treatment should continue as long as tinnitus persists. Carbamazepine was not found to be effective in reducing tinnitus. Thus, Piracetam and Gabapentin are effective as a modality of treatment in suppressing tinnitus according to this study. CONCLUSION: Tinnitus does not represent disease itself but instead is a symptom of a variety of underlying diseases. Otologic causes include noise-induced hearing loss, presbycusis, otosclerosis, otitis, impacted cerumen, sudden deafness, Meniere’s disease, and other causes of hearing loss. Because tinnitus is a subjective symptom, we used the subjective scale—the Tinnitus Handicap Index—as the only parameter. In our study, we concluded that use of Piracetam helps in reducing tinnitus and also improve sensorineural hearing loss in patients with tinnitus and the treatment should continue as long as tinnitus persists. Carbamazepine was not found to be effective in reducing tinnitus. Thus, Piracetam and Gabapentin are effective as a modality of treatment in suppressing tinnitus according to this study. We hope that our outcomes will be helpful for patients suffering from chronic tinnitus. Acknowledgment: 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 the authors/editors/publishers of all those articles, journals and books from which the literature for this article has been reviewed and discussed. Source of funding: none Conflict of Interest: none Authors’ Contribution: Dr.AnaghaRajguru: lead researcher and guide Dr.Kaenat Ahmed: second author and corresponding author Dr.Lakshmi SravyaYarlagadda: third author Dr. Samiksha Karna: forth author and data corresponding Ethical Clearance: KIMSDU/IEC/17/2019 Englishhttp://ijcrr.com/abstract.php?article_id=4411http://ijcrr.com/article_html.php?did=4411 Scherer R, Formby C. Effect of Tinnitus Retraining Therapy vs Standard of Care on Tinnitus-Related Quality of Life. JAMA Otolaryngology–Head & Neck Surgery. 2019;145(7):597.  Aazh H, El Refaie A, Humphriss R. Gabapentin for Tinnitus: A Systematic Review. AJOA. 2011;20(2):151-158. Penner MJ. An estimate of the prevalence of tinnitus caused by spontaneous otoacoustic emissions. Archives of otolaryngology-Head and Neck Surgery.1990; 116:418-23.  Pujol R.Lateral and medial efferents: A double neurochemical mechanism to protect and regulate inner and outer hair cell function in the cochlea. British Journal of Audiology.1994; 28:185-91. d’Aldin C, Eybalin M, Puel JL, Charachon G, Ladrech R, Renard N et al. Synaptic connections and putative functions of the dopaminergic innervation of the guineapig cochlea. European Archives of Otorhinolaryngology.1995; 252:270-4.  Bobbin RP, Jastboff PJ, Fallon M, Littman T. Nimodipine, an L-channel Ca++ antagonist, reverses the negative summating potential recorded from the guinea pig. Hearing Research.1990; 46:277-88. . Dobie RA. Clinical trials and drug therapy for tinnitus. In: Snow J, ed. Tinnitus: Theory and Management. Hamilton, Ontario, Canada: BC Decker; 2004:266-277. .Parnes SM. Current concepts in the clinical management of patients with tinnitus. Eur Arch Otorhinolaryngol. 1997;254(9-10):406-409. doi:10. 1007/BF02439968 . Martinez-Devesa P, Perera R, Theodoulou M, Waddell A. Cognitive behavioural therapy for tinnitus. Cochrane Database Syst Rev. 2010;(9): CD005233. . Jastreboff PJ. Phantom auditory perception (tinnitus): mechanisms of generation and perception. Neurosci Res. 1990;8(4):221-254. doi: 10.1016/0168-0102(90)90031-9  Gold SL, Formby C, Gray WC. Celebrating a decade of evaluation and treatment: the University of Maryland Tinnitus & Hyperacusis Center. Am J Audiol. 2000;9(2):69-74. doi:10.1044/1059-0889 (2000/014) Jastreboff PJ, Hazell JWP. Treatment of tinnitus based on a neurophysiological model. In: Vernon J, ed. Tinnitus and Relief. Boston, MA: Allyn & Bacon; 1998:201-217. Simha V, Ravishankar S. N Comparative Study to Determine the Efficacy of Piracetam over Carbamazepine in the Treatment of Idiopathic Tinnitus. International Journal of Innovative Research in Medical Science (IJIRMS). 2017 ;02(07):1015-1017.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareMorphological, Phytochemical and Fourier-transform Infrared Spectroscopy (FTIR) Spectroscopic Analysis of Selected Species of Portulacaceae: A Study English7179Beulah Jerlin SEnglish Santhiya Raichel MEnglishIntroduction: Morphological characters of plants to assess the differences or similarities in plant taxa and use these characters for plant identification. And also an attempt is made in the present study to analyze the functional group of active compounds present in the leaf and stem extract of selected species of Portulacaceae. Objective: To study morphological, phytochemical and Fourier-transform infrared spectroscopy (FTIR) spectroscopic analysis of selected species of Portulaceae. Methodology: Physical examination and measurement of physiognomic features of fresh floral and vegetative sections of the plants were used to conduct a morphological study on the genus Portulaca. Phytochemicals were screened and analyzed with standard methods. 2,2-diphenyl-1-picrylhydrazylquenching assay were selected to investigate antioxidant free radical scavenging activity respectively. Result: Morphologically they are dissimilar. Leaves are needle in P. grandiflora and obovate in P. umbraticola. Petals are numerous in P.grandiflora and 5 in P. umbraticola. The result of preliminary phytochemical screening indicated that leaf and stem of both species. Both plants were free from steroids. Moreover, quantitative estimation of phytochemicals also exhibited the leaf and stem of both species. Secondary metabolites, which are abundant in plants and have fascinating biological activities, are an important source with a variety of structural arrangements and properties. They have a rich source of protein and have high antioxidant scavenging activity. Conclusion: Both species of Portulacaceae carry rich protein and have high therapeutic values. Therefore further efficacy and safety studies are encouraged on this potential herb with the hope of replacing some less effective ones in clinical practice especially for antidiabetic and anticancer. EnglishPortulaca grandiflora, Portulaca umbraticola, Morphology, FTIR spectroscopy, DPPH, PhytochemicalsINTRODUCTION Plants are major sources of traditional medicines with a large variety of bioactive constituents, which are effective against different diseases. The dependence of man on plant resources is as old as the various human civilizations. Plant-derived drugs are still a valuable resource in the fight against serious diseases, particularly in developing countries. Since ancient times, higher plants have played a dominant role in the preservation of human health as sources of medicinal compounds.1 Medicinal plants are used by people all over the world to treat a variety of human and animal diseases. These bioactive constituents are responsible for the plants' major biological activities. Medicinal plants are rich sources of antibacterial and antifungal agents and are used as sources of potent and beneficial drugs in many countries.2 Some ornamental plants  are  grown for medicinal purposes because they contain a variety of bioactive compounds such as phenolic compounds, carotenoids, antioxidants, essential oils, and other secondary metabolites.3 Ornamental plants like Ocimum sp., Nicotiana sp., Ixora, Aloe vera, Agave, etc. Roses, nasturtium, hibiscus, marigold, Calendula, and other ornamental flowers are widely cultivated in homes and have a variety of medicinal uses. Furthermore, plant-based remedies can be much less expensive and have less side effects than pharmaceutical-based medications in terms of protecting against free radicals. Phytochemicals are compounds found in medicinal plants, leaves, vegetables, and roots that act as a protective mechanism and provide protection against a variety of diseases. Phytochemicals are primary and secondary compounds. Chlorophyll, proteins and common sugars are included in primary constituents and secondary compounds have terpenoid, alkaloids and phenolic compounds.4 According to some generous estimates, almost 80% of the present day medicines are directly or indirectly obtained from plants.5 Any material that delays or inhibits oxidative damage to a target molecule is considered an antioxidant.6 The main characteristic of an antioxidant is its ability to trap free radicals. Antioxidant compounds such as phenolic acids, polyphenols, and flavonoids scavenge free radicals like peroxide, hydroperoxide, and lipid peroxyl, inhibiting the oxidative processes that cause degenerative diseases.7               FTIR used for the identification of functional groups of the compounds present in the sample.8 FTIR enables infrared spectrum measurements to be done quickly and accurately on a wide variety of biological specimens.9 Plant based medicines are safe and effective for the treatment of many ailments. Phytochemical screening is helpful to detect the various important compounds which could be used as the base of modern drugs for curing various diseases. Keeping this in mind the investigator selects the two plants from Portulacaceae the purslane family of flowering plants, in the order Caryophyllales. Portulaca grandiflora, Hook.is a common garden plant in Japan. The entire plant is depurative. Hepatitis, cirrhosis of the liver with ascites, swelling, and pain in the pharynx are all treated with it. Externally, the fresh juice of the leaves and stems is used to treat snake and insect bites, burns, scalds, and eczema.           Portulaca umbraticola, also known as the wing pod purslane, is a perennial succulent in the genus of flowering plant Portulaca. While it is easy to confuse this species with P. oleracea, the foliage of this species is much smaller and wider than that of other species. Roots are edible. In reality, it contains more nutrients than spinach. It has no bitter taste and can be consumed raw or fried. It's best for soups and stews because of its mucilaginous consistency. Seeds can be eaten raw or ground and used to make bread. Hence, the present work is aimed at with the following objectives To find out the Morphological characters to eliminate possible confusion to identify them. To assess the status of phytochemical properties of leaf and stem of Portulaca grandiflora and Portulaca umbraticola. To analyze the phytochemicals quantitatively. To identify the functional group of phytochemicals by using FTIR spectroscopy. To evaluate the antioxidant activity of leaf and stem samples of Portulaca grandiflora and Portulaca umbraticola by using DPPH free radical assay. MATERIALS AND METHODS Collection and processing of the plant materials Portulaca grandiflora and Portulaca umbraticola were collected from the home garden of Thoothukudi. The Leaf and stem of Portulaca grandiflora and Portulaca umbraticola were cut into pieces, sun dried to reduce the moisture level. The plant material was pulverised after drying to obtain a coarser powder material, which was then deposited in an airtight plastic container. About 10 g of each fine powdered sample was weighed and separately soaked in 100 ml of Methanol and distilled water. These were permitted to sit at room temperature for 24 hours. All the extracts were filtered through Whatman No. 41 filter paper and the filtrate was used for further analysis. Preliminary Phytochemical Screening (Qualitative analysis): The qualitative phytochemical test for tannins, saponins, carbohydrate, protein and phenol were carried out on the concentrated extracts using the standard procedures.10 flavonoids and quinones by Kokate.11 Coumarins, terpenoids and steroids are by Yadev.12 Alkaloids, carbohydrate, glycosides, protein and phenol were carried out on the concentrated extracts using the standard procedures to identify the constituents in leaf and stem of Portulaca grandiflora and Portulaca umbraticola. PHYTOCHEMICAL QUANTITATIVE ESTIMATION Total Soluble Protein.13 100 mg of sample was homogenized in 10 ml of distilled water and filtered through a muslin cloth and centrifuged at 3000 rpm for 10 minutes. To the supernatant 10% trichloro acetic acid (TCA) was added in 1:1 ratio and left in an ice bath for 30 minutes to precipitate protein. The supernatant was then discarded after centrifugation at 3000 rpm for 5 minutes. In 0.1N sodium hydroxide, the precipitate was dissolved and diluted to a known amount. 5 mL alkaline copper reagent was applied to 0.5 mL protein extract. After thorough mixing 0.5 ml of folin ciocalteu reagent was added and allowed to stand for 30 minutes; the blue colour appeared and absorbance was measured at 650 nm using UV visible spectrophotometer (Model No: UV 2371). The analysis was performed in triplicates and the amount of protein was calculated and expressed as mg/g DW. Estimation of Carbohydrate The total carbohydrate content was determined.14 An aliquot of 1ml sample (1mg/ml) was mixed with 5ml of 5% phenols and conc. Sulfuric acid. Tubes were vortexed and incubated for 15 minutes at a boiling water bath. After cooling to room temperature, the absorbance was measured against blank at 490 nm using a UV-VIS spectrophotometer. Total flavonoid.15 Procedure 100 mg of sample was homogenized with 10 ml of distilled water and filtered through muslin cloth. 0.5 ml of extract was added with 2.5 ml distilled water and mixed. After 6 minutes, 0.15 ml NaNO was added and again after 6 minutes, 0.3 ml of 10% AlCl3 was added. After 5 minutes 1 ml of 1M NaNH and 0.5% ml of water were added. The absorbance against a blank was measured at 510 nm after the solution had been thoroughly mixed. Quercetin was used as standard and the results were expressed as mg quercetin equivalents (QE)/g dry weight Vitamin-C (Ascorbic acid)16 100 mg of each sample was homogenized with 10 ml of 5% trichloro acetic acid (TCA). The homogenate was centrifuged at 3000 rpm. To 2 ml of protein free supernatant, 1 drop of indophenol reagent and 0.5 ml of DT reagent were added and incubated at 10°C for 1 hour. Then cooled in an ice bath and 2.5 ml of 85% sulphuric acid was added. After intermittent shaking for 30 minutes (until red colour appeared), 30 absorbance was measured at 540 nm. L-ascorbic acid was used as standard and the results were expressed as mg/g DW. Vitamin E (Tocopherol).17 The sample (2.5 g) was homogenized in 50 ml of 0.1 N sulphuric acids and allowed to stand overnight. The content in the flask was shaken vigorously and filtered through Whatman No.1 filter paper. Aliquots of the filtrate were used for estimation. Into stoppered centrifuge tubes, 3 ml of extract and 3 ml of water were pipetted out separately. To both the tubes, 3 ml of ethanol and 3 ml of xylene were added, mixed well and centrifuged. The Xylene (2.0 ml) layer was transferred into another stoppered tube. To each tube, 2.0 ml of dipyridyl reagent was added and mixed well. The mixture (3 ml) was pipetted out into a cuvette and the extinction was read at 460 nm. Ferric chloride solution (0.66 ml) was added to all the tubes and mixed well. After 15 minutes, the red colour formed and read at 520 nm.  ANTIOXIDANT ACTIVITY Crude sample extracts were prepared by pouring 100ml of distilled water in a conical flask containing 10g of each sample separately in the ratio of 10:1 (V/W). After 24 hours, the mixture was filtered through whatman no:1 filter paper and the filtrate was  evaporated to dryness. Crude (aqueous) extracts of all samples (1mg/ml) were used for the determination of free radical scavenging activity. Free radical scavenging assay.18 Free radical scavenging assay was measured by 2-2 Diphenyl, 1-picryl hydrazine (DPPH) method proposed with slight modifications. 1ml of aliquot of test sample was added to 3ml of 0.004% DPPH solution prepared in methanol. The absorbance was measured at 517 nm after the mixture was vortexed for 1 minute and held at room temperature for 30 minutes in darkness. Allow absorbance of the reaction mixture indicated a high free radical scavenging activity. Ascorbic acid was used as standard. DPPH scavenging activity (%) A control –A test / A control * 100 Where, A control is the absorbance of the DPPH solution without test solution. A test is the absorbance of DPPH with the test solution. Aqueous extract was used as blank. FT-IR Spectroscopy: Using a mortar and pestle, a small amount of plant specimen powder was combined with KBr salt and compressed into a thin pellet. Infra-red spectra were recorded as KBr pellets on a Thermo Scientific NicotiS5ID1 transmission, between 4000-400 cm-1. RESULT The morphological characters of the studied taxa are presented in (Table1). Both taxa were ornamental perennial herbs. In P.grandiflora stem are whitish herbaceous, prostate, cylindrical thick and succulent with scarcious or hairy stipular appendage. Leaves are needle like, simple alternate one leaf per node along the stem, small group at the end of the branched. The flowers are solitary, axillary, bisexual, small groups at the end of branches, but flowers only flourish one after another and come in various colours. Flowers bracteates, hermaphrodite, actinomorphic, showy, complete and hypogynous. The lifespan of flowers is one day they are open during day time. Subconnate at the base, sepals 2, green in colour persistent, united at the base. Petals many, obovate with entire margin. Stamens 8-9 in one whorl, adnate to petals inserted on calyx, filaments basally connate, about 2.5-6 mm long, anthers 2-4 locular, dorsifixed. Semi inferior, unilocular ovary with 4-many ovules on free central placentation, type 5 fid, 8-13 mm long, stigmas 5 linear, 2.5-3 mm long. (Table 2) QUALITATIVE PHYTOCHEMICAL SCREENING The preliminary phytochemicals screening of leaf and stem of selected plants such as Portulaca grandiflora and Portulaca umbraticola were presented in Table 3. Leaf samples of P.grandifloracontain Flavonoids, Alkaloids, Glycosides, Terpenoides, Betacyanin and Quinones were present in aqueous solution. Flavonoids, Alkaloids, Glycosides carbohydrates Terpenoides, Quinones and Anthraquinone were present in Methanol extract. Leaf extract of P. umbraticola containing Alkaloids, Glycosides, Protein, Terpenoids, and Betacyanins were present in aqueous solution. Alkaloids, Glycosides, Coumarins and Anthraquinone were present in methanol extract. Stem samples of P.grandiflora contain Alkaloids, Protein and Betacyanin were present in aqueous solution. Flavonoids, Alkaloids, Carbohydrates, and Anthraquinone were present in methanol extract. Stem of P. umbraticola possible presence of Saponins, Flavonoids, Alkaloids, Carbohydrates, Betacyanin and Anthraquinone in the methanol extracts. Alkaloids and Anthraquinone were present in aqueous extracts. The result of preliminary phytochemical screening indicated that tannins, saponin, phenol and steroids are totally absent in both the species. QUANTITATIVE ANALYSIS More amount of Protein was observed in the stem than the leaf. Carbohydrates and Flavonoids were poor in all the samples. Vitamin E is higher than Vitamin C. The level is maximum in all the samples. Carbohydrates are very less. The results were presented in Table 4. The results of anti–oxidant DPPH scavenging activity shows more percentage in stem than leaf of P.umbraticola. In Portulaca pilosa leaf shows more than stem. The result is present in Table 5. Based on the peak value in the infrared radiation region, the FTIR spectrum was used to classify the functional group of the active components. The results of FTIR peak values and functional groups were represented in Table 6-9. Fig.1-4. The FTIR spectrum confirmed the presence of alcohols, phenols, alkanes, alkynes, alkyl halides, aldehydes, carboxylic acids, aromatics, nitro compounds and amines in different samples. DISCUSSION Morphological characters of selected species of Portulacaceae were dissimilar. Leaves are needles in P.grandiflora Obovate in P. umbraticola. This was proven by earlier literature of Shide.19,20 Phytochemicals are substances that carry multiple biological properties. Preliminary phytochemical screening of both samples shows the possible presence of Alkaloids, Glycosides, Protein, Terpenoids, Coumarins, Carbohydrates, Anthraquinone and Betacyanins. The important thing is that Flavonoids were present in all samples.  Flavonoids are an economically valuable main class of secondary metabolites and are good for human health and also help the plants to protect against adverse environmental conditions.21,22 By using FTIR spectrum, we can confirm the functional group. This result coincides with previous observations by various biologists.23 DPPH scavenging activity of P.grandiflora Obovate is more than P. umbraticola. 24 Conclusion Morphologically they are dissimilar. Leaves are needle in  P.grandiflora and obovate in P.umbraticola. Petals are numerous in P.grandiflora petals are 5 in P. umbraticola. The result of preliminary phytochemical screening indicated that leaf and stem of both species. Both plants were free from steroids. Moreover, quantitative estimation of phytochemicals also exhibited the leaf and stem of both species. The plant's rich source of secondary metabolites with interesting biological activities in general these secondary metabolites are an important source with a variety of structural arrangements and properties. They have a rich source of protein and have high antioxidant scavenging activity. Therapeutic value is also rich. Therefore further efficacy and safety studies are encouraged on this potential herb with the hope of replacing some less effective ones in clinical practice especially for antidiabetics and anticancer. ACKNOWLEDGEMENT This research is a part of the M.Sc project of second author. Authors gratefully acknowledge St. Mary’s College (Autonomous) Thoothukudi. For providing an enormous resource and peaceful environment for the successful project completion. Conflicts of Interest: The author reports no conflict of Interest. Source of Funding: Nil Englishhttp://ijcrr.com/abstract.php?article_id=4412http://ijcrr.com/article_html.php?did=4412 Farombi. E.O. 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Int J Pharm Pharm Sci . 2014. Vol 6 Issue (5):539-542.       13. Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J. "Protein measurement with the Folin phenol reagent". J Biol. Chem,1951. Vol 193 Issue (1): Pp 265–75.        14. Dubois M, Gilles K.A, Hamilton J.K, Rebers, P. A. J, Calorimetric Dubois method for Determination os sugar and related substance, Analytical Chemistry. 1956. Vol 28 Issue (3) PP 350-356.      15. Zhishen J. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chemistry,1999. Vol .64, PP.555-559, Available from: Accessed: Mai. 2013. doi: 10.1016/S0308-8146(98)00102-2. ZUR, I.A. et al. Cytological analysis of infection proc.     16. Baker H, Frank O Tocopherol. Methods and Interpretation, New York Interscience Publisher, John Wiley and Sons, Inc, 1968 Clinical Vitaminology.PP 172-3.    17. Rosenberg, H. R., Chemistry and Physiology of the Vitamins.1992. Inter Science Publisher Inc.    18. Hatano T, Kagawa H, Yasuhara T, Okuda T. Two new flavonoids and other constituents in Licorice root: their        relative astringency and radical scavenging effects Chemical and Pharmacetical Bulletin., (1988), Vol 36 Issue (6) pp. 2090-2097 19. Shinde P. R, Wagh K. R, Patil P. S, Bairagi V. A. Pharmacognostic standardization and antibacterial potential of aerial herbs of Portulaca grandiflora Hooker (Portulaceae). WJPS 2014. ISSN (Print): 2321-3310; ISSN (Online): 2321-3086. 20. Netala S, Priya AM, Pravallika R, Tejasri NS, Sumaiya Shabreen Md, Nandini Kumari S. Comparative Pharmacognostic Studies on Three Species of Portulaca. IJPPR. 2014. Vol 6 Issue (4), PP 704-714.    21. Kumar V, Suman U, Rubal, Kumar S, Yadev, Flavonoid Secondary Metabolite: Biosynthesis and role in growth and development in plants. Recent trends and techniques in plant metabolic Engineering 2018. pp 19-45   22. Lakshmi T, Geetha R.V, Anitha Roy Acacia Catechu Willd: IJCRR  2012 Vol 03 Issue 05, PP 101-111  23. Sahayaraja APJ,Gowri a* V, Dharmalingama R, ShobanaaA. Angelin Premab Phytochemical screening by FTIR spectroscopic analysis of leaf and stem Extracts of wedelia biflora Int. j. nano corros. sci. eng. (2015) Vol 2 Issue (5) PP 322-334.   24. Chithra, Dharanyshri , Das A, Bindhu  Structural and Antimicrobial Analysis of Methanolic Extract of Punica granatum PEEL A. IJCRR 2021 Vol 13 Issue (3) PP 175-184.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareNon-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma English8085Divya Meenu PreethaEnglish Yuva BalakumaranEnglish PravithaEnglishIntroduction: Cholesteatomas are lesions that develop in pneumatized areas of the temporal bone, such as the middle ear and mastoid, or both, and are extremely rarely detected in the external auditory canal. Because it has benefits over CT, diffusion-weighted imaging MRI (DWI-MRI) can be a useful technique in the identification of cholesteatoma. Image distortion and artefacts are less visible with non-echo planar imaging DWI techniques than with other DWI techniques. Aims and Objectives: 1) To assess the usefulness of HRCT scan in Chronic suppurative otitis media (CSOM) with cholesteatoma in depicting the status of the middle ear structures. 2) To correlate HRCT findings of temporal bone with surgical findings in Chronic suppurative otitis media (CSOM) with cholesteatoma with respect to the following parameters: Presence or absence of cholesteatoma, Extent of cholesteatoma, Status of ossicular chain, Integrity of the facial canal, Detection of erosions or dehisence in the bony labyrinth, and Detection of erosions or dehisence in the dural or sinus plates. 3) Comparison with Non-Echo planar imaging diffusion-weighted for presence or absence of cholesteatoma. 4) 3D FIESTA Magnetic resonance imaging with 3D reconstruction of membranous vestibule and cochlea for better delineating associated complications. Materials and Methods: Total 40 patients of clinically suspected CSOM with cholestaetoma were enrolled for this study. All patients were scanned using a non-contrast High-resolution computed tomography technique and MRI. HRCT findings were noted according to the proforma. MRI DWI was recorded as either positive or negative for cholesteatoma & directly correlated with post-surgical presence or absence of cholesteatoma.3D FIESTA for detection of membranous labyrinthine erosion/defect was correlated with surgical findings of bony labyrinthine erosions. Results: Cholesteatoma was shown to be common in the third decade of life in our study. The most often implicated middle ear structures in our investigation were the epitympanum, aditus, and antrum. The most often eroded ossicle is the stapes, followed by the incus. The tympanic section of the facial canal is the most often affected segment, while the posterior semicircular canal is the most commonly degraded of the bony labyrinth structures. Conclusion: HRCT temporal bone, in combination with non-echoplanar DWI MRI and 3D Fiesta, can help with accurate diagnosis and pre-operative assessment of cholesteatoma. EnglishNon-echoplanar diffusion, 3D fiesta magnetic resonance imaging, High resolution computed tomography, Temporal bone, Chronic suppurative otitis media, CholesteatomaIntroduction: Cholesteatomas are lesions that develop in pneumatized areas of the temporal bone, such as the middle ear and mastoid, or both, and are extremely rarely detected in the external auditory canal. They are non-neoplastic, locally invasive masses that often appear as unilateral lesions. Cholesteatomas are categorized into three types: congenital, which affects only children, acquired, which affects both adults and children, and unclassifiable, which is a cholesteatoma whose origin cannot be established correctly .1 The extent of a cholesteatoma is still difficult to identify with current imaging techniques because of its makeup, especially in ears that have already undergone surgery. The standard modality has been computed tomography (CT), which allows for the detection of bone alterations. Diffusion weighted imaging MRI (DWI-MRI) can be a useful technique in the identification of cholesteatoma since it has benefits over CT, such as a shorter examination duration and no requirement for a contrast medium injection prior to the test.2 Because of its high sensitivity and specificity, DWI-MRI may detect tiny collections of keratin debris that would otherwise be misinterpreted as fluid or edematous mucosa on CT and is capable of detecting recurrent cholesteatoma.2,3 Three-dimensional fast imaging with steady-state acquisition (3D-FIESTA) pictures were introduced recently. 3D-FIESTA imaging can provide significantly better spatial resolution and excellent picture contrast. It takes less time to acquire images than a traditional MRI scan and does not require contrast media.4,5 Materials and methods: This prospective study was conducted at Radio-Diagnosis at Vinayaka Missions Kirupananda Variyar Medical College Hospital, Salem. Total 40 Patients with cholestaetoma and clinically suspected CSOM were enrolled in this study. Before enrolling in the trial, all patients gave their written informed consent. Inclusion criteria were patients with clinically suspected atticoantral type of chronic suppurative otitis media of all age   groups and either sex; patients willing to give consent. Patients with previous ear surgeries, patients with a history of temporal bone trauma, patients with neoplastic development involving the middle ear, and patients unwilling to give consent were all excluded. A complete history of ear discharge, deafness, tinnitus, earache, vertigo, headache, and fever was collected and recorded in a systematic order, with specific attention to any accompanying symptomatology suggestive of any imminent or already established chronic otitis media complication. All patients were scanned using a non-contrast HRCT on GE revolution CT scanner. The axial sections were acquired in a supine, neutral position, parallel to the superior orbital-meatal line consecutively. Scanning was done extending from the petrous pyramid to the mastoid in spiral mode. The gantry rotation time was 1 s and acquisition parameters were 6 × 1 mm with slice collimation of 1 mm, slice thickness of 2 mm, and increment of 2 mm. Multiplanar reconstruction in axial, coronal, and sagittal planes was performed at a slice thickness of 1.25 mm and an increment of 0.8 mm. MRI was performed on a 1.5-T (Siemens) with use of the standard Head Matrix coil. Axial propeller DWI for all cases and 3D Fiesta was performed in selective cases and when required. HRCT findings were noted according to the proforma. Intraoperative findings of mastoid exploration surgery were recorded and were taken as standard for determination of sensitivity and specificity of HRCT scan for various study variables. The data were analyzed using descriptive statistic tools like proportions. MRI DWI was recorded as either positive or negative for cholesteatoma & directly correlated with post surgical presence or absence of cholesteatoma.3D FIESTA for detection of membranous labyrinthin erosion/defect was correlated with surgical findings of bony labyrinthin erosions. Results: In present study, 65% of the respondents are male and 35% of the respondents are female.30% of the respondents are less than 20 years, 25% of the respondents are in the age group 21-30, 15% of the respondents are in the age group 31-40 and 22.5% of the respondents are in the age group 41-50 and 7.5 % of the respondents are above 50. Majority of patients had Ear discharge 36(90%), 32(80%) had earache, 22(55%) had hearing loss, 10(25%) had facial weakness and 5(12.5%) had Giddiness, vomiting, others. In majority of patients had cholesteatoma on right side 27(67.5%)  and 13 (32.5%) on left side. Since the p-value for the are less than (p-values Englishhttp://ijcrr.com/abstract.php?article_id=4413http://ijcrr.com/article_html.php?did=44131.    Yung M, Tono T, Olszewska E, Yamamoto Y, Sudhoff H, Sakagami M, et al. EAONO/JOS Joint consensus statements on the definitions, classification and staging of middle ear cholesteatoma. J Int Adv Otol. 2017;13:1–8. 2.    Henninger B, Kremser C. Diffusion-weighted imaging for the detection and evaluation of cholesteatoma. World J Radiol. 2017;28:217–222. 3.   Corrales CE, Blevins NH. Imaging for evaluation of cholesteatoma: current concepts and future directions. Curr Opin Otolaryngol Head Neck Surg. 2013;21:461–467. 4.    Erdogan N, Altay C, Akay E, Karakas L, Uluc E, Mete B, et al. MRI assessment of internal acoustic canal variations using 3D-FIESTA sequences. Eur Arch Otorhinolaryngol. 2013;270:469–475. 5.    Rigby PJ. Comparison of FIESTA and gadolinium-enhanced T1-weighted sequences in magnetic resonance of acoustic schwannoma. Radiographer. 2006;53:11–21. 6.    Chee NWC, Tan TY. The value of pre-operative high-resolution CT scans in cholesteatoma surgery. Singapore Med J 2001;42(4):155-159. 7.  Jackler KR, Dillon PW, Schindler AR. Computed tomography in suppurative ear disease: A correlation of surgical and radiographic findings. Laryngoscope 1984;94(6):746-752. 8.    Barath  K,  Huber AM,  Stampfli  P, Varga  Z, Kollias S.    Neuroradiology of cholesteatomas. AJNR 2010;10.3174:1-9. 9.    Gaurano LJ, Joharjy AI. Middle ear cholesteatoma:characteristic findings in 64 patients. Ann Saudi Med(online) 2004;24(6):442-447. 10.  Mafee F M, Levin CB, Applebaum LE, Campos M, James FC.Cholesteatoma of the middle ear and mastoid: A comparison of CT scan and operative findings. Otolaryngologic clinics of North America 1998;21(2):265-292. 11.    Leighton SE, Robson AK, Anslow P, Milford CA. The role of CT imaging in the management of chronic suppurative otitis media. Clin Otolaryngol Allied Sci 1993; 18: 23-9 12.    Gaurano LJ, Joharjy AI. Middle ear cholesteatoma: characteristic findings in 64 patients. Ann Saudi Med 2004;24(6):442-447. 13.    Chee NWC, Tan TY. The value of pre-operative high-resolution CT scans in cholesteatoma surgery. Singapore Med J 2001;42(4):155-159. 14.    Alzoubi FQ, Odat HA, Al-balas HA, Saeed SR. The role of preoperative CT scan in patients with chronic otitis media. Eur Arch Otorhinolaryngol 2009; 266:807–9. 15.  Jackler RK, Dillon WP, Schindler RA. Computed tomography in suppurative ear disease: A correlation of surgical and radiographic findings.  Laryngoscope 1984; 94: 746-52. 16.    Leighton SE, Robson AK, Anslow P, Milford CA. The role of CT imaging in the management of chronic suppurative otitis media. Clin Otolaryngol Allied Sci 1993; 18: 23-9. 17.    De Foer B, Vercruysse JP, Bernaerts A, Maes J, Deckers F, Michiels J, et al. The value of single-shot turbo spin-echo diffusion-weighted MR imaging in the detection of middle ear cholesteatoma. Neuroradiology2007;49:841–48. 18.    Williams MT, Ayache D, Alberti C, Héran F, Lafitte F,. Detection of postoperative residual cholesteatoma with delayed-contrast-enhanced MR imaging: initial findings. Eur Radiol2003;13:169–74.  

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15Healthcare COVID-19 and the Ethics of WHO to Treat First: A Utilitarian Approach English8691Linus Oluchukwu AkudoluEnglish Ikechukwu Kenneth OkwuosaEnglish Charles N. OkolieEnglish Edward Ajanwachukwu OkoroEnglish Hillary O. EzeEnglish The scarcity of resources in healthcare is always a problem. The problem is worsened by rising cases of coronavirus, mounting pressure on the available limited resources. The ethical issue emanating from this situation is the problem of whom to treat first. In the midst of scarce medical resources, who shall receive medical attention first? Between an ordinary patient and victim of coronavirus, between the critical and mild victim, and between the aged and the young, who shall be treated first? The paper adopted a utilitarian approach in solving the problem. The finding is that the number of persons to benefit from treating a particular patient, duration of treatment, age and health condition of the patient, chances of recovery, and quality of life after recovery are factors to be considered in taking the ethical decision. The work is qualitative research using library materials such as journal articles, books and unpublished materials as sources of data, while hermeneutics and philosophical analysis are applied in studying them. EnglishCOVID-19, Coronavirus, Pandemic, Utilitarianism, Medicals Resource Allocation, Medical ethics INTRODUCTION The scarcity of resources in healthcare is always a problem. The problem is worsened by rising cases of coronavirus, mounting pressure on the available limited resources. It would be proper to recall that the virus which causes the respiratory tract infection Covid-19 was detected first in the city of Wuhan, China, in November 2019. The outbreak spread with unprecedented velocity across the world within the first months of 2020 and was declared a worldwide pandemic on 11th March, 2020 by World Health Organization. A pandemic is when a communicable disease is passing so fast from person to person in many countries at the same period of time. From China, many parts of Europe and North America was beaten majorly by April, 2020, but as they began to witness a reduction in the outbreak, Latin America, Asia and Africa started to witness rapid case spikes. The outbreak spread to all parts of the globe in such a way that there was tumult, confusion and fear of global cleansing. Governments all over the world were forced to close their borders, limit public movements and shut down businesses and venues in order to limit the rate of the spread of the virus. Total lockdown, social distancing, shut down of social gathering, face mask order, use of sanitizer, constant washing of hands and numerous policies were enforced to checkmate the spread of the virus, but to no avail. The statistics of the cases kept on rising daily, defying all policies and attempts to checkmate the pandemic. Though the true statistics of the cases is not easy to gather and document, due to secrecy, inadequate data collection and management, poor testing equipment and communication gaps in many nations, the Visual and Data Journalism Team of BBC news was relentless in gathering what we can lay hands-on with a view of giving cursory information on the outbreak to the populace. The data, according to them, come from various sources, including figures collated by World Health Organization, Johns Hopkins University, and European Centre for Disease Prevention and Control, UN data on populations and data from various national governments and health agencies.1 According to BBC report, as of  21st June 2021, more than 178.4 million cases have been confirmed so far all over the world, with more than 3.8 million victims already dead as a result of the virus.2 Cases of the disease have continued to increase in many nations, while some that witnessed apparent success in controlling the initial outbreaks are now seeing an upsurge in the spread of the infections. This development and upsurge led many countries to re-impose total lockdowns in their worst-affected parts of their nations, and renew appeals for people to wear face masks and to observe the rule of social distancing. With this upsurge, the number of patients competing to access medical facilities in these nations outweighs the available facilities. In many nations, the retired medical personnel have been recalled to join hands in handling the challenges; Governmental and Non-Government Organizations, philanthropists and religious organizations have donated medical facilities and resources, yet the problem of scarce medical facilities and personnel is not yet totally solved.  The ethical issue emanating from this situation is the problem of whom to attend first. In the midst of scarce medical resources, who shall receive medical attention first? Between an ordinary patient and victim of coronavirus, between the critical and mild victim, and between the aged and the young, who shall be treated first? Savulescu and Wilkinson asks “Who gets the ventilator in the coronavirus pandemic?” Imagine there are two patients with respiratory failure…” 3 It is undeniable fact that people should have an equal chance when there are sufficient resources. Someone should not be denied medical treatment due to his age, sex, disability, race or other factors. Such action would be partiality and unfair treatment, but not when the resources are very scarce and could not go round them. So, how can we ration the available resources when they are not adequate? Responding to these questions, this paper adopts utilitarianism as a good ethical approach. It explains the meaning of utilitarianism, and compares it with other resource allocation principles in healthcare, and highlights reasons why utilitarianism is a better option than others. It points out how utilitarianism can be applied practically in solving the problem of whom to treat first in time of pandemic. This paper concludes with certain recommendations and admonitions. MATERIALS AND METHODOLOGY Considering that this work is qualitative research in medical ethics, we sourced our data from various medical experts in the form of oral interviews and discussions on the issue. We also consulted many library materials such as journal articles, books and unpublished materials. And considering that the topic borders on ethics and value judgment, we applied philosophical skills such as hermeneutic interpretation, critical and logical reasoning (both induction and inductive reasoning), and analysis in studying the data to minimize the influences of sentimentalism and prejudice. Nevertheless, the research of this kind cannot be purely objective, but we believe its findings passed a rational acceptability test and relevance to scholars of bioethics and medical practitioners. DISCUSSIONS Understanding the Ethical Approach: Utilitarianism Utilitarianism is a moral philosophy of Jeremy Bentham and John Stuart Mill that emphasizes the greatest number of good to the greatest number of people. It was an influential philosophy due to its simplicity and its way of conforming to what people already believed in their time that pleasure and happiness are what people desire. From this simple fact that everybody desires pleasure and happiness, the utilitarians inferred that the whole idea of what is good can be understood in the principle of happiness, which they spoke as “the greatest good of the greatest number”, and by which they meant that ‘good’ is achieved when the aggregate of pleasure is greater than the aggregate of pain and when an action gives happiness to the greatest number of people.4 An action is good if it is used in achieving pleasure and reducing pain to the greatest number of persons; that is, if it is useful and beneficial to the greatest number of persons. In other words, utilitarianism is a class of normative ethical theories that encourages actions that maximize happiness and well-being for greater number of persons.5 Although there are different versions of utilitarianism with different characterizations, the basic idea that they all share is the emphasis on maximizing utility, which is often defined in terms of usefulness or greatest benefit to the greatest number or related concepts. For instance, the founder of utilitarianism, Jeremy Bentham (1780)  describes utility as that quality in any object or action, whereby it tends to produce, advantage, benefits,  good, pleasure or happiness...[or] to prevent the happening of evil, pain, suffering or unhappiness to the person or persons involved.6 It would be a mistake for one to think that Bentham utilitarianism is not concerned with the formulation of rules. For according to him, the business of the government or anyone that serves the public is to minimize pain to the public, while the happiness of people increases. In Chapter VII of his book, An Introduction to the Principles of Morals and Legislation, Bentham says that the ends of legislation are maximization of pleasure and minimization of pain. By pleasure, he didn’t mean sexual and animalistic pleasure but the good, welfare and happiness of man. Bentham 6 insists that "The business of government is to promote the happiness of the society, by punishing and rewarding.… In proportion, as an act tends to disturb that happiness, in proportion as the tendency of it is pernicious, will be the demand it creates for punishment" (p.1). Speaking on the principle of utility, Bentham says: Nature has placed mankind under the governance of two sovereign masters, pain and pleasure. It is for them alone to point out what we ought to do.… By the principle of utility is meant that principle which approves or disapproves of every action whatsoever according to the tendency it appears to have to augment or diminish the happiness of the party whose interest is in question: or, what is the same thing in other words to promote or to oppose that happiness. I say of every action whatsoever, and therefore not only of every action of a private individual but of every measure of government (p.1). In Chapter IV, Bentham introduces a hedonic calculus, which is a method of calculating the value of pleasures and pains. According to him, the value of a pleasure or pain, can be measured according to how intense it is, its duration, certainty, propinquity, purity and the number of persons to be affected. He also introduces the concepts of evils of the first and second order. Evils of the first order has more immediate consequences but evils of the second order are those that have consequences that can affect members of the community or many people causing pain or loss or danger to many people. This of course is a greater evil. Therefore, in a situation where action would bring pain to an individual if it is done and pain to the community if it is left undone, the action must be taken to save a greater number of people. You should not allow the whole community to perish because of an individual but can sacrifice an individual to save many. John Stuart Mill, a disciple of Jeremy Bentham, was brought up with a view of carrying out the cause of utilitarianism.7 His book, Utilitarianism appeared first in Fraser’s Magazine as a series of three in 18618 and was published in 1863 as a single book.9 Mill did not accept a quantitative measurement of utility. According to him, some kinds of pleasure are more valuable and desirable than others. In other words, quality must be considered and not only quantity as Bentham held. For Mill, the word utility means general well-being or happiness, and his view is that utility is the end of a good action. For him, utility in the context of utilitarianism refers to people performing actions for social utility. With social utility, he implies the well-being or good of many people. His explanation of the concept of utility in his book, Utilitarianism, is that people really long for happiness, and since each individual desires their individual happiness, it must follow that all of us must desire the happiness of everybody, contributing to a greater social utility. Thus, an action that has a favorable consequence to the greater number in the society is considered the best action; or as Bentham, the founder put it, the greatest happiness of the greatest number. Mill did not only view actions as a core part of utility, but as a guide to moral human conducts. The rule is that we should only be committing actions that give pleasure to society and not selfish pleasures and satisfactions. Pleasure is therefore seen by both Bentham and Mill as the highest good in life, which is hedonism. According to them, good actions result in pleasure or happiness. There is no higher end than pleasure. Pleasure defines good character. Better put, what justifies character or action as being good or not, is based on whether it produces pleasure or happiness, the quantity and quality of pleasure, and the number of persons involved (social utility). Though, the proponents of utilitarianism differ on number of points but agree that social utility remains the best action expected from man; action that gives greatest service to the greatest number of persons. Therefore, utilitarianism is a version of consequentialism, which states that the consequence of an action is what makes it right or wrong. It is contrary to egotism and altruism as it considers collective interest in decision making, and tries to maximize the greatest possible service or social utility to the greatest number of people in society. Actions done for the interest of the community is better than the one that serves an individual selfish interest.10  Utilitarianism and other Resource Allocation Approaches in Healthcare Delivery One popular approach to the issue of whom to treat first in many hospitals at sundry is egalitarianism: the principle of “first come, first served”. Egalitarianism argues equal treatment for equal need 11-12 and that no factor should be used to discriminate against any person from receiving medical treatment.3 Therefore anyone that comes first should be treated first. Imagine there are ten patients, the one that came first was an old man of 85 years suffering from covid-19, and may likely be on ventilator for weeks and is likely to die due to his old age and other related health challenges, and there is another patient who can make use of the ventilator for just 24hours and is likely to survive because he is stronger: Who among them shall be treated first? If health workers insist on allowing the old man who came first to access the available ventilator for weeks, it may result in deaths of other patients. And there is a great possibility that the old man would not survive after using the ventilator. Is this not a bad decision? The man is not saved and others too lost. The man, even if he is saved, is likely to die soon due to his age and other health challenges. More so, saving the life of such an old man who has little or nothing to contribute in life at the expense of the lives of other able men seems very absurd.  Another principle is the severity of the patient. Critical patients are given immediate attention to save them. This is why hospitals do have emergency units. The Emergency Department is a very vital aspect in the healthcare community. The emergency room is used for the purpose of giving urgent attention to patients in critical condition.13 Many at times, patients arrive to the emergency room through ambulance, ranging from accident victims to unexpected injuries and sudden critical illness.14 Considering the severity of emergency patients in giving them attention first is very ethical and reasonable, but this cannot serve as a general approach to the case of whom to treat first, because there may be possibility that all the patients are critical and the medical resources scarce. On the other hand, there may be a situation where none is critical. More so, there may be a situation where there is a coronavirus patient and an ordinary critical patient in the emergency room. In this situation, who should be attended first?  In other words, severity is not a general criteria or principle that applies in all circumstances but in exceptional and emergency cases only. Obviously, many medical practitioners consider the socio-economic status of patients. Social status plays a great role in people’s influences and regard, but is not an ethical ground on the issue of whom to treat first, as it amounts to discrimination. Similarly, other factors such as the possibility of survival, quality of life after survival, duration of treatment and host of others are very relevant but must be considered in line with the principle of utilitarianism.15 Utilitarianism as we have seen considers the number of persons to benefit from treating a particular patient first. It, therefore, considers the interests of many other than individualism; it is community-oriented, and that is why we consider it the best approach to the issue of whom to treat first in the time of pandemic. Pandemic threatens the world with global cleansing, and utilitarianism being a principle that considers the salvation of others in the treatment of an individual is therefore recommended. Application of Utilitarianism It is an undeniable fact that people should have equal access when there are sufficient medical resources. As noted before, no one should be denied medical treatment that is available on ground of his sex, age, race, disability or any other factor. Such discrimination is unfair and immoral. But when the resources are scarce and could not go round, certain factors must be taken into account in deciding who would be given priority. Imagine there are many coronavirus patients in a hospital. The first patient is 85 years old COVID-19 infected man, with severe dementia, who has been staying invalid in a nursing home. The second person is also a critical coronavirus patient, a young man of 40, with four kids and wife depending on him for survival.  There are also other young and prospective patients with diverse serious cases waiting in the queue. The hospital has only one ventilator. The old man, the young man of 40 and a great number of the patients need the ventilator too.  Who among these should be treated first when the resources are scarce? If the doctor insists on treating the old man first, who is likely to be on ventilator for a longer period of time due to his age, with little chances of survival, and minimal years to be enjoyed when cured, the young man of 40 as well as great number of persons on the queue may die.  Moreover, the old man is already invalid, and his death, though may be painful to his people but would not make them to be liabilities to society. In fact, his death would be a blessing to them in disguise as they are relieved of the burden of taking care of him. His survival is of little or no benefit to the society at large. On the other hand, the death of the young man is a colossal loss to his wife, four children, dependent relatives, community and larger society, both emotionally, socially and economically. The young still have a quality life to live, many impacts to make and his usage of the ventilator may not be long, giving chance to others to use and be saved. By implication, the young man should be given priority over the old man. RESULTS Utilitarianism, therefore, holds that resources should be utilized to save the greatest number. According to utilitarianism, medical officers should take actions that bring about the most good. They must take decisions that would enable them save many lives with limited resources than to waste them on a single or few patients. 5 It is better to lose one and save many than to save one and lose many.  In order to achieve this, they need to take the following factors into consideration: 1.    Number:  One obvious factor to be considered in application of this principle is number. This is the stand of Bentham when he talks about quantity. According to utilitarianism, facilities should be used to bring about the greatest good for the greatest number. If you can save ten people, or one, you ought to save the ten. You also have to consider the number of persons to be happy if a particular patient is cured and the number to suffer as a result of his death.    2.    Duration of Treatment: To save the greatest number of people, duration of treatment must be considered. Between a person who is likely to stay longer on a ventilator and one who is likely to stay for a shorter period, who should be treated first? Treating a person that is likely to stay longer on a ventilator would increase the number of deaths.  3.    Age and Health Condition: Similar to the duration of treatment is age and health condition of a patient. Aged coronavirus patients and those with other health challenges stay longer in ventilators, consume more medical resources and hardly survive the attack of the virus. In Italy, age and health conditions are so much considered. A document from Northern Italy states: "The criteria for access to intensive therapy in cases of emergency must include age of less than 80 or a score on the Charlson comorbidity index [which indicates how many other medical conditions the patient has] of less than five" (see Savulescu and Wilkinson 2020)3. So if one is more than 80 years or has other medical challenges of more than five, he would not be treated. This is because “What might be a relatively short treatment course in healthier people could be a longer and more resource consuming in the case of older or more fragile patients”.15  In Niguarda, doctors decline life-prolonging treatment to patients over the age of 60. Are we to blame them for taking such a cruel decision? We mustn't not because the resources are insufficient. The number of patients outweighs the available resources. Therefore, they must decide whom to be saved first with the scarce resources and whom to be neglected or allowed to die, if God wills. 4.    Certainty/Chances of Recovery: Bentham also emphasizes on certainty, probability of recovery. A doctor should not waste the limited resources on a patient who is likely to die, while others that are likely to survive are allowed to die. Such action is wicked and unethical. A wise doctor should consider treating the younger persons and others whose cases give assurance of recovery. Old people and those with complicated health challenges hardly survive the attack of coronavirus, and that is why in many countries, they are left untreated. 5.    Quality of Life after Recovery: Mill9 in his book, Utilitarianism highlights the importance of quality of life in utilitarian decisions. According to him, some kinds of pleasure are more valuable and desirable than others. In other words, quality must be considered. We must consider the state of life after recovery, its usefulness, and the expected life span. Between a coronavirus victim who is more than 80 and has been invalid on bed as a result of a stroke and a young man of 40, who is to be cured? The young man still has many years to live if God wills; he is still active, useful and has more visions to fulfill. Such a case needs less argument. He deserves attention first.    How can we apply utilitarianism in cases between ordinary patients and COVID-19 patients? Who is to be treated first? The same factors apply. We have to consider how urgent the patient needs the medical facilities, the number of facilities to be consumed, chances of survival, age and health condition, quality of life after recovery etc. A question may be raised on the issue of quality of life after treatment. How about a young man who is a criminal and has been terrorizing the community? Should we treat him before an old man, who though is very old but has better character than the young man? This is not an easy question to answer. But we have to reason: How many people would die if we embark on treating the old man? You don’t just consider the quality of life alone but the totality of the factors. Truly, utilitarianism cannot easily solve all the issues and challenges behooving medical practitioners in times of pandemic but is indeed a veritable guide in managing the insufficient resources in face of an outlandish number of patients. RECOMMENDATIONS Life is very important and should be preserved at all costs. As we said in the beginning, selecting those to be treated and allowing others to die is very unfair, but not when the resources are insufficient to go round. When the resources are limited and the number of patients competing to access the resources is greater than the available resources, medical officers should consider certain individuals first before others, using utilitarian principles, which advocates greater happiness to the greatest number of persons. Utilitarianism gives us a better guide on how to make acceptable choices in such a situation to minimize the effect of limited resources. It shows us how the limited resources can be maximized to the benefit of many. This is the best approach to handle the issue of limited resources in times of the pandemic. But if the resources are sufficient and all things good and fine, ceteris paribus, there is no need to evoke such an approach. In order to avoid such an ugly situation, we recommend the following: 1.    Government, Non-Governmental Organizations and philanthropists should join hands in providing the requisite health facilities in time of the pandemic. Pandemic is very challenging as the number of patients often increases more than the available resources. All hands must be on deck to tackle this problem, otherwise, health officers would be forced to make decisions on who to live and who to die. 2.    Private hospitals should be called upon to assist. Many countries' policy of restricting private hospitals from the management of pandemics like coronavirus is very unhealthy. If they feel that they are not trained to handle such issues, why not give them ad-hoc training to ease government hospitals? 3.    Retired health workers need to be recalled to assist in such a period. Some countries did so during this era of coronavirus while some insist on using few health workers in active service. The peculiar problem needs peculiar attention and less protocol.  4.    Public Enlightenment. The public needs to be enlightened on how to minimize the chances of getting the infection. This can be done through mass and social media. 5.    The necessary policies such as social distancing, use of sanitizer, frequent washing of hands with runny water, restriction of movement and social gathering need to be enforced. People are too stubborn and at times need to be forced to follow these rules and save their lives and the lives of many. 6.    Families with aged people and persons with health challenges should take serious precautions to protect them from getting the virus as their chances of survival are very minimal. 7.    Palliative should be given to citizens to ease their suffering and create a conducive atmosphere necessary for these rules to be obeyed. The reason why lockdown did not work out in many countries was hunger. People are hungry and must go out to earn a living.16 Its consequence is the daily increase of new cases. 8.    Era of a pandemic is not an opportunity to make money. Many politicians pay lip service to the problem of coronavirus. The funds earmarked for the procurement of medical facilities and tackling the problem were embezzled in many nations. This is a bad omen. CONCLUSION In conclusion, egalitarianism and other approaches to the case of whom to treat first may be good but not in an era of the COVID-19 pandemic when the available medical resources are insufficient compared to the number of patients. Since the situation already on the ground in many nations is beyond human control, we have to adapt utilitarianism as an alternative ethical approach to limit the effect of the virus and save many lives. Utilitarianism as we have seen is a kind of consequentialism that is against egotism as it seeks the interest of the greatest number of people in society. We know that the interest of society is better than that of an individual. Though the application of the utilitarian approach is not so easy, but having highlighted some factors which health practitioners should put in consideration, we hope that the challenge is half-solved. COMPLIANCE WITH ETHICAL STANDARD Acknowledgment: Mrs Nkiruka Uzoagu, who proofread this work and helped to enhance the grammar. Source of Funding: No grant was received for this work Conflict of Interest: None Originality: This work has is original research. It has not been be submitted simultaneously or published elsewhere. Approval on involvement of Animal: No animal is involved, and therefore not applicable. Approval on involvement of Human Being: No human being was mentioned in this work, and therefore not applicable. Authors’ Contribution Dr. Linus Oluchukwu Akudolu is a team leader as well as the scribe to this work, while Ikechukwu Kenneth Okwuosa, Dr.Charles N. Okolie, Dr. Edward AjanwachukwuOkoro, and Hillary O. Eze contributed in provision of data, materials and group discussions that resulted to this work.   Englishhttp://ijcrr.com/abstract.php?article_id=4414http://ijcrr.com/article_html.php?did=4414 BBC. Coronavirus Pandemic: Tracking the Global Outbreak. 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Educational reform and value re-orientation for the preservation of African communalistic principles. International Journal of Social, Politics and Humanities, 2019; 2 (1):1-5. https://zambrut.com/communalistic-principles/ Dworkin R. Sovereign virtue: Equality in Theory and Practice. Cambridge: Harvard University Press, 2000. Eslung D. Liberalism, equality, and fraternity in Cohen’s critique of Rawls. J Polit Philos, 1998; 6:99-112. Department of Emergency Care. Vishwaraj Hospital. https://vishwarajhospital.com (Acessed on 22nd June, 2021). CxbcoOrdination. Importance of Hospital with high-quality emergency room. Health. https://Cxbcoordination.org (Acessed on 22nd June, 2021) Mounk Y. The Extraordinary Decisions Facing Italian Doctors. The Atlantic, 11th March 2020. https://www.theatlantic.com/ideas/archieve Akudolu L, Eze O. An ethical concern on gender-based violence against women and girls in Africa during COVID-19 lockdown. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareMultiple Swellings on the Tongue of a Young Female: Report of a Rare Case English9294Ranjanee SrinivasanEnglish Shruthi AcharyaEnglish Ravindranath VineethaEnglishIntroduction: Lymphatic malformations are a part of low- flow lesions of the lymphatic channels. Due to increased lymph in the head and neck region, nearly 70% of lesions occur in these locations. They can manifest in the cheeks, tongue, around the alveolar ridge of the mandible and parotid gland. Lymphangioma of tongue can be a difficult entity for diagnosis as it is less frequently encountered. So, it is crucial for dental physicians to know about this condition for precise diagnosis and early treatment. Case Report: A 16-year-old female reported with multiple swellings and enlarged tongue with difficulty in speech. The swellings were painless with no evidence of bleeding. There was no associated symptoms of fever or lymphadenopathy. Her medical history was non-contributory. Discussion: In this case report, the clinical presentation and management of oral lymphangioma is briefly described Conclusion: As oral diagnosticians, we should be aware of the conditions associated with oral vascular malformations to correlate with underlying systemic diseases providing holistic and multi-speciality management strategies. EnglishLymphangioma, Lymph vessels, Macroglossia, Vascular malformation, Cystic hygroma, TongueIntroduction: A vascular malformation is a diverse group of disorders that includes capillary, venous and lymphatic malformations. Since these disorders have several syndromic associations, patients with these lesions should be critically evaluated for underlying systemic illnesses. It is of utmost importance for oral health professionals to understand and identify this condition for prompt referrals and multi-disciplinary management. Objective statement: To describe the clinical picture of oral lymphangiomas CASE REPORT: A 16-year-old female reported to the Department of Oral Medicine and Radiology, Manipal with a complaint of multiple swellings on the tongue for the past 6-7 months. She also reported of an enlarged tongue, which gradually increased to the present size with difficulty in speech. The patient did not report difficulty breathing. The swellings were painless with no evidence of bleeding. There were no associated symptoms of fever or lymphadenopathy. Her medical history was non-contributory. There was no extra-oral swelling or facial asymmetry. On intra-oral examination, (FIG. 1,2) there was evidence of an enlarged tongue with multiple, yellow to pink bubbles and nodules of varying sizes seen on the ventral aspect of the tongue seen resembling “Tapioca pudding”. On palpation, the swellings were non-tender and soft in consistency with no active bleeding. With these clinical pictures, a provisional diagnosis of lymphangioma of the tongue was given. The patient was advised a Contrast-Enhanced Computed Tomography (CECT) scan of the tongue which showed evidence of well-defined small isodense mass on the ventral surface of tongue having mild homogenous enhancement with no calcifications, fat components and intense enhancement suggestive of possible low-flow vascular malformation (FIG. 3). Following CECT, patient was advised surgical management and histopathological evaluation. The patient did not report back due to financial constraints. DISCUSSION: Lymphatic malformations are a part of low-flow lesions of the lymphatic channels. The lesions are believed to originate due to sequestration of primitive anlage or due to stasis of regional lymphatics. Due to increased lymph in the head and neck region, nearly 70% of lesions occur in these locations. They can manifest in the cheeks, tongue, and around the alveolar ridge of the mandible and parotid gland. Lymphangioma of the tongue can be seen as multiple small swellings known as “Frog’s egg” appearance or the “Tapioca pudding” appearance. In mucosal involvement, there may be small translucent bubbles filled with blood, yellow to pink in colour with a pebbly appearance. Huge lesions tend to cause infiltration into adjacent structures and patients may experience respiratory obstruction.1 There can be acute exacerbations during certain respiratory infections and fluctuation of hormones at puberty.2 Based on the size of the lymphatic spaces, the lesions are categorized as macrocystic and microcystic.3 The immune-histochemical marker ‘Podoplanin D2-40’ is positive in lymphatic malformations and aids in diagnosis. Lymphatic malformations form a part of few syndromes including Gorham- Stout syndrome and CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular malformation, Epidermal nevi and Skeletal anomalies).4 MRI is the choice of imaging as it enables to view the extent of the lesion and its association with the adjacent tissues without any penetrating radiation.5 Treatment include surgery, sclerosants, laser, cryotherapy and embolization. CONCLUSION: Arteriovenous malformations are quite frequent lesions in routine dental practice. So it is imperative for the oral physicians to be aware of the condition, its differential diagnosis, and medical and surgical management. ACKNOWLEDGEMENTS The authors thank the patient and patient’s parents for their cooperation. The authors acknowledge the contribution of scholars whose articles are cited in this manuscript. Conflict of interest: None Source of funding: NIL Declaration by the patient: Informed consent was signed by the patient Author’s contribution: Dr Ranjanee Srinivasan- Patient examination, diagnosis and contribution to the manuscript Dr Shruthi Acharya- Patient examination, diagnosis and contribution to the manuscript Dr Ravindranath Vineetha- Contribution to manuscript. Englishhttp://ijcrr.com/abstract.php?article_id=4415http://ijcrr.com/article_html.php?did=44151.        Mahady K, Thust S, Berkeley R, Stuart S, Barnacle A, Robertson F, et al. Vascular anomalies of the head and neck in children. 2015;5(6):886–97. 2.        Brahmbhatt AN, Skalski KA, Bhatt AA. Vascular lesions of the head and neck: an update on classification and imaging review. Vol. 11, Insights into Imaging. Springer; 2020. 3.  Hoff SR, Rastatter JC. Head and Neck Vascular Lesions. Otolaryngol Clin NA [Internet]. 2015;48(1):29–45. Available from: http://dx.doi.org/10.1016/j.otc.2014.09.004 4.        Nozaki T, Nosaka S, Miyazaki O, Makidono A, Yamamoto A, Niwa T, et al. Syndromes associated with vascular tumors and malformations: A pictorial review. Radiographics. 2013;33(1):175–95. 5.      Flors L, Leiva-Salinas C, Maged IM, Norton PT, Matsumoto AH, Angle JF, et al. MR imaging of soft-tissue vascular malformations: Diagnosis, classification, and therapy follow-up. Radiographics. 2011;31(5):1321–40.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareA Study of Thyroid Profile (FT3, FT4, TSH) in Liver Cirrhosis in Jharkhand - A Hospital-based Study English95100Vishwanath Malkappa JalawadiEnglish Upendra Prasad YadavEnglish Ajit DungdungEnglish Bindey KumarEnglish Rashmi SinhaEnglishIntroduction: Because thyroid hormones and liver hormones are so closely linked, thyroid hormone abnormalities can be found in people with liver disorders. Aim: To determine the prevalence of thyroid dysfunction in liver cirrhosis patients. Materials and Methods: This case-control study was carried out in a group of randomly selected liver cirrhosis patients in the Department of Medicine at Rajendra Institute of Medical Sciences (R.I.M.S), Ranchi, Jharkhand (India) between September 2017 to August 2018. The equal number of age (>18 years) and sex-matched cases &controls were included in this study. Radioimmunoassays were used to evaluate early morning fasting blood thyroid-stimulating hormone (TSH), serum total free thyroxine (FT4), and free triiodothyronine (FT3) in 100 index patients with liver cirrhosis who had no history of thyroid disorders. Results: In the cases that were studied, which consisted of cirrhotic patients, males (80%) outnumbered females (20%). The mean age of cases was 47.9 years, and the maximum numbers of the patient were between 41-55 years of age group (47%). Among the cirrhotic patients, the commonest etiology was alcoholic liver disease which contributed to 78% of the total cases studied. The rest of the cases included cirrhotics from other etiologies, which included NAFLD (22%), HBsAg positive individuals (07%), and other cases of cryptogenic origin. The mean FT3, FT4, and TSH values in cases were 2.29±0.83; 1.20±0.55 & 3.76±2.43 respectively & the mean FT3, FT4, and TSH of the control group were 2.95±0.52; 1.40±0.25 & 2.70±0.94 respectively. From these data, we can say that there is significant derangement of thyroid function in liver cirrhosis in favor of hypothyroidism (pEnglishFT3, FT4, TSH, Hypothyroidism, Liver cirrhosis, NAFLDINTRODUCTION: The liver is thoroughly involved in proteins, cytokines and interleukins synthesis and destruction. Therefore, abnormal function of endocrine organs is expectable in patients with liver cirrhosis. Similar processes to those seen in sick euthyroid syndrome can occur in several types of liver illness. Still, there are also a variety of modifications specific to the type or stage of liver disease.              The liver monitors and controls the transport, catabolism, and excretion of the thyroid hormones. Thyroxin binding globulin (TBG), the main transport protein of thyroid hormones, is synthesized in the liver and binds over seventy-five percent of the circulating hormones.1Therefore, dysregulation and dysfunction of thyroid hormones are anticipated in patients with liver cirrhosis.2 According to research utilizing [131I] T4, the liver extracts 5–10% of plasma T4 in a single passage. This result is significantly larger than the quantity of free T4 transported to the liver, implying that there is a significant amount of protein-bound T4 accessible for uptake.3 Although hypothyroidism was more frequently seen in cirrhosis, hyperthyroidism has also been reported in patients with cirrhosis.4 T3 and FT3 concentrations are usually decreased in correlation with the severity of the disease, but this is still controverted.5 This is probably due to reduced deiodinase one activity and subsequent impaired hepatic conversion of T4 to T3.6 There are three homologous iodothyronine deiodinases that catalyze these reactions.7,8 Type I deiodinase is located in the liver, kidney, and thyroid. In addition to the deiodination to activate and deactivate thyroid hormones, the liver has an essential role in thyroid hormone transport and metabolism.9              The endocrine system is a complex, sophisticated system that involves many physiological and pathological processes and functions in the human body. Thyroid hormones regulate BMR in all cells, including hepatocytes, and are necessary for the appropriate growth, development, and function of all tissues of the body. Thyroid hormones are metabolized by the liver, which modulates their systemic endocrine effects. Normal thyroid function is required for optimal cell growth, development, and metabolic energy regulation and depends on a normally functioning thyroid and liver axis. Thyroid dysfunction can affect liver function, and liver disease can affect thyroid hormone metabolism9, and both organs are affected by a number of systemic diseases.10             In individuals with non-thyroidal diseases, low total and free T3 with normal total T4 and thyrotropin concentrations have been often recorded in the absence of clinical hypothyroidism.11-13 In a prospective investigation of 118 individuals with cirrhosis, ultrasonography revealed a 17 percent increase in thyroid glandular volume as compared to controls.14             Low total and free T3 levels may be regarded as an adaptive hypothyroid state that helps to sustain liver function and total body protein reserves by lowering the basal metabolic rate inside hepatocytes. Indeed, a recent study in cirrhotic patients found that the advent of hypothyroidism during cirrhosis due to intrinsic thyroid illness of various etiologies resulted in a biochemical improvement in liver function (e.g., coagulation profile) when compared to controls. Hypothyroidism has also been linked to a lower degree of cirrhosis breakdown.15 Controlled hypothyroidism may thus be advantageous in cirrhotic patients, but more research is needed to confirm this concept.             The liver has an important role in thyroid hormone metabolism because it is the manufacturer of proteins that bind thyroid hormones, such as thyroid-binding globulin (TBG), pre-albumin, and albumin. It is also the major site of thyroid hormone peripheral metabolism and is involved in its biliary conjugation excretion, oxidative deamination, and the extrathyroidal deiodination of thyroxin (T4) to triiodothyronine (T3) and to reverse T3.16 On the other hand, the level of thyroid hormone is also important to the normal hepatic function and bilirubin metabolism17,18. Conceivably, the disorders of these two organs would interact or influence each other. As liver abnormalities worsen, the T3 production from T4 is also reduced.             It is believed this reduction of T3, which mainly corresponds to an even lower basic metabolism rate, economically can be useful due to preventing extra energy waste and keeping it for the onset of liver disease or any other related syndrome which consumes further energy. Free T3 concentration corresponds with the state of liver disease, and it seems the serum T3 concentration is directly related to liver abnormalities progress. Furthermore, it is demonstrated that levels of thyroid hormones and their binding proteins are altered in patients with hepatic disorders, especially cirrhosis19; however, almost all are clinically euthyroid.20These thyroids liver associations may cause diagnostic confusion, and neglect of these facts may result in over or under-diagnosis of associated liver or thyroid diseases. Therefore it is suggested to measure free T4 and TSH levels to rule out the coexistent possibility of thyroid dysfunction in any patient with unexplained liver biochemical test abnormalities.6 MATERIAL AND METHODS: The study was carried out in a group of randomly selected liver cirrhosis patients in the Department of Medicine at RAJENDRA INSTITUTE OF MEDICAL SCIENCES(R.I.M.S)Ranchi, Jharkhand (India), from September 2017 to August 2018, which was preapproved by the Ethical Committee of this institution review board.  Equal age (>18 years) and sex-matched controls were included in this study. Patients were selected by adhering strictly to certain inclusion and exclusion criteria mentioned underneath. Inclusion criteria: Age more than 18 years. Both sexes will be included. Patients with evidence of liver cirrhosis by ultrasonography. The patient/attendant must give informed consent. Exclusion criteria: Patients with a history of recent clinical infection, surgery, or major trauma in the previous month. Patients in shock Patients with metabolic abnormalities Patients with a previous/present history of hypothyroidism/ hyperthyroidism. Study design: Case-control study. Period of study:  September 2017 to August 2018. Sample size:200 participants were enrolled for the present study. 100 Patients with evidence of liver cirrhosis by ultrasonography were selected for the study during the study period and 100 participants were without evidence of liver cirrhosis& metabolic abnormalities served as controls. Method of sampling: Early morning fasting serum thyroid-stimulating hormone (TSH), serum total free thyroxine (FT4), and free triiodothyronine (FT3) were measured by radioimmunoassays in 100 index patients with liver cirrhosis who did not have a history of thyroid diseases. Statistical method: We have analyzed the statistical data by using SPSS statistical software version-20, Descriptive statistics i.e., Mean and Standard deviation (SD) for the continuous variables, and frequency distribution and their percentage for categorical variables were calculated. Independent T-test was calculated for significance. p-value less than 0.05 was considered as the statistical significance level.  RESULTS : Table-1 is showing 80% of males and outnumbered females (20%) among the cases, and 85% males and 15% females among the control group. TABLE 2 The mean age of cirrhosis occurrence among cases was determined to be 47.90 years in table -2 above. TABLE 3 According to table-3 the Maximum numbers of cases were between 41-55 years of age group (47%), and only 2 cases were in 71-85 years of age group. TABLE 4 Above table-4 is showing alcoholic cirrhosis is the most common cause (78%), other causes include NAFLD (22%), HBsAg +ve (07%) & no one was Anti HCV +ve. The above table-5 is showing mean FT3, FT4 & TSH among cases are (2.29±0.83),(1.20±0.55) & (3.76±2.43 ) and in controls (2.95±0.52), (1.40±0.25), (2.70±0.94) respectively and is statistically significant (pEnglishhttp://ijcrr.com/abstract.php?article_id=4416http://ijcrr.com/article_html.php?did=4416 Williams DL and Goodburn R. The thyroid gland in biochemistry in clinical practice. New York, Heinemann, 1983; PP.562-3. Eshraghian A, Taghavi SA. Systematic Review: Endocrine Abnormalities in Patients with Liver Cirrhosis. Arch Iran Med. 2014; 17(10): 713 – 721. Mendel CM, Cavalieri RR, Weisiger RA. Uptake of thyroxine by the perfused rat liver: implications for the free hormone hypothesis.  Am J Physiol. 1988;255:E110-19.  Silveira MG, Mendes FD, Diehl NN, Enders FT, Lindor KD. Thyroid dysfunction in primary biliary cirrhosis, primary sclerosing cholangitis, and non-alcoholic fatty liver disease. Liver Int. 2009; 29: 1094 – 1100.  Sheridan P: Thyroid hormones and the liver. J Clin Gastroenterol 1983; 12: 797– 818. Huang MJ, Liaw YF. Clinical associations between thyroid and liver diseases. J Gastroenterol Hepatol. 1995; 10: 344 – 350. Larsen PR, Berry MJ. Nutritional and hormonal regulation of thyroid hormone deiodinases. Annu Rev Nutr. 1995;15:323-52. Visser TJ. Pathways of thyroid hormone metabolism. Acta Med Austr. 1996;23:10 11. Malik R, Hodgson H. The relationship between the thyroid gland and the liver. QJM 2002;95:559–69. Amita Y, Sarika A, Vandana S, Megha KA, Ritu S, Jayashree B. Influence Of Thyroid Hormones On Biochemical Parameters Of Liver Function: A Case-Control Study In North Indian Population; Internet Journal Of Medical Update. 2013 January; 8(1):4-8.  Chopra IJ, Soloman DH, Hepner GW, Morgenstein AA. Misleadingly low free thyroxine index and usefulness of reverse triiodothyronine measurement in nonthyroidal illnesses. Ann Intern Med 1979; 90: 905–12. Kaptein EM, Weiner JM, Robinson WJ, Wheeler WS, Nicoloff JT. Relationship of altered thyroid hormone indices to survival in non-thyroidal illnesses. Clin Endocrinol 1982; 16: 565– 74. Bermudez F, Surks MI, Oppenheimer JH. High incidence of decreased seruμm triiodothyronine concentration in patients with nonthyroidal disease. J Clin Endocrinol Metab 1975; 41: 27–40. Bianchi GP, Zoli M, Marchesini G, Volta U, Vecchi F, Iervese T, et al. Thyroid gland size and function in patients with cirrhosis of the liver. Liver 1991; 11: 71-7. Oren R, Sikuler E, Wong F, Blendis LM, Halpern Z. The effects of hypothyroidism on liver status of cirrhotic patients. J Clin Gastroenterol 2000;31:162-3. Kaplan M. & Utigw D. Iodotbyronine metabolism in rat liver homogenates. J Clin Invest 1978; 61:459-74. Goglifa F,  Liverini G, Lanni A, Lossa S, Barletta A. The Effect of thyroid state on respiratory activities of three rat liver mitochondrial fractions. Mol. Cell. Enub & Wl. 1989; 62 41-6.https://doi.org/10.1016/0303-7207(89)90111-1  Fagiuolsi I & Van Thield H. The liver in endocrine disorders. In: Rustgi V. K. & Van Thiel D. H., eds. The Liver in Systemic Disease. Raven Press, New York, 1993; 285-7 Yamanaka T, Ido K, Kimura K, Saito T. Serum levels of thyroid hormones in liver diseases. Clin Chin Acta 1980; 14: 45-55. Borzio M, Caldara R, Borzio F, Piepoli V, Rampini P, Ferrari C. Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. Gut 1983; 24: 631-6. Deepika G, Veeraiah N, RaoPN, Reddy ND. Prevalence Of Hypothyroidism In Liver Cirrhosis Among Indian Patients; International Journal Of Pharmaceutical And Medical Research Volume (WJPMR)– 3 Issue – 3 June 2015; Issn: 2348-0262.  Vincken S, Reynaert H, Schiettecatte J, Kaufman L, Velkeniers B. Liver cirrhosis and thyroid function: Friend or foe Acta Clin Belg. 2017 Apr; 72(2):85-90. Joeimon J L, Mohanraj K, Karthikeyan R, Rajkumar Solomon T, Aravind A, Caroline Selvi K; Thyroid Dysfunction in Patients with Liver Cirrhosis; IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861. Volume 16, Issue 4 Ver. VIII (April. 2017), PP 18-22   Punekar P, Sharma AK, Jain A. A Study of Thyroid Dysfunction in Cirrhosis of Liver and Correlation with Severity of Liver Disease. Indian J Endocrinol Metab. 2018 Sep-Oct;22(5):645-650. 

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareResults of Low-profile Plates in the Treatment of Distal Radius Fractures: A Longitudinal Study at Our Institute English101104Muhammad Tahir LakhoEnglish Najeeb U RehmanEnglish Imtiaz Ahmed TagoEnglish Zahoor Illahi SoomroEnglish Rakesh Kumar GuptaEnglish Dilawar KhanEnglish Niaz Hussain KeerioEnglishIntroduction: Distal radius fracture (DRF) is a common injury that can happen to anyone. Cast treatment, with or without closed reduction, has long been considered a viable alternative for DRF treatment. Aim: The purpose of the study was to assess how low-profile plates treat unstable and intra-articular distal radial fracture (DRF) in terms of clinical, functional, and radiological outcomes. Methodology: This study comprised 40 distal radius fractures treated with fragment selective fracture therapy because they were unstable and intraarticular. The Mayo wrist score was used to assess wrist function and reported postoperative problems. The researchers were looking for people over the age of 20, with closed unstable distal radius fractures, and closed intraarticular distal radius fractures. A longitudinal study. This study was conducted at, Dow University & Dr Ruth K.M.Pfau Civil Hospital Karachi Pakistan from March 2020 to March 2021. Results: The participants’ ages ranged from 20 to 60, with a median age of 37 years. Fractures were most common in people between the ages of 42 and 50 years. In this study, there were n=23 (57.5%) male patients and n=17 (42.5%) female patients. The right side fracture was present in n=28 (70%) patients and in n=12 (30%) patients on the left side. The Mayo scoring system was used to analyze the results. Out of forty patients, twenty-one patients had outstanding results, ten had reasonable results, and nine had acceptable results. Conclusion: Low-profile plates improve clinical and functional outcomes in the treatment of intra-articular DRF by providing secure fixation, allowing early joint mobilization, and improving all above outcomes. EnglishDistal radius fracture, Invasive plate fixation, Palmar locking plate, Outcomes, Treatment, Surgical techniquehttp://ijcrr.com/abstract.php?article_id=4434http://ijcrr.com/article_html.php?did=4434

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcareThe Severity and Outcome of Acute Hepatitis in Patients Presenting with Dengue Fever: A Cross-sectional Study       English105109Muhammad KaleemEnglish Rizwan ChannaEnglish Muhammad Adnan BawanyEnglish Raja RavenderEnglish Ruqayya FarhadEnglish Yar Muhammad TunioEnglishIntroduction: Dengue fever is an arboviral infection spread by the mosquitoes Aedes agepty and Aedes albopictus. The majority of these instances have been documented in Southeast Asian locations, which are popular tourist destinations. Aim: To assess the severity and outcome of acute hepatitis in patients presenting with dengue fever. Methodology: The study included all patients under the age of 14 who were hospitalized with a diagnosis of Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), or Dengue Shock Syndrome (DSS). The Chi-Square test and, when appropriate, the Fischer exact test were employed to compare categorical variables. For the primary outcome, a survival analysis (Cox regression and log-rank) was performed. To compare continuous variables, the student test was utilized. Significance was defined as a p-value of less than or equal to 0.05. Cross-sectional study. This study was conducted at Suleman Roshan Medical College Hospital Tando Adam Pakistan from January 2020 to January 2021. Results: Total 500 cases were included in the study, with 87 % (435) having DF and 13% (65) having DHFs or DSS. The median ALT was 87.91 IU/L; IQR 42.78-181 IU/L, the median AST was 179 IU/L; IQR 85-369.3 IU/L, and the median T.Bil was 0.8 mg/dl; IQR 0.6-1.3 mg/dl, according to liver function tests. A total 71 % (355) of the patients had mild to moderate hepatitis, whereas 15 % (75) had severe hepatitis. In patients with mild/moderate hepatitis, the average length of stay (LOS) was 3.63 days, compared to 4.3 days in those with severe hepatitis (P-value 0.002). Overall mortality in the mild/moderate hepatitis group was 36.84% (n = 7) compared to 63.15% (n = 12) in the severe hepatitis group (p-value 0.001). The severe hepatitis group (H.R (4.91; 95 % CI 1.74-13.87 and P-value 0.003), as well as the DHF/DSS group, had substantially increased mortality (H.R (5.43; CI 1.86-15.84 and P-value 0.002). In the mild/moderate and severe hepatitis groups, there was a substantial difference in sequelae such as bleeding (P-value 0.001), Acute Renal Failure (ARF) (P value 0.002), Acalculus cholecystitis (P-value 0.04), and encephalopathy (P-value 0.02). Conclusion: In Dengue fever, severe hepatitis (ALT>300IU) is linked to a longer length of hospital stay, mortality, hemorrhage, and renal failure. Apart from typical hepatotropic viruses, dengue fever should be evaluated when liver tests are abnormal. EnglishDengue fever, Hepatitis, Dengue Hemorrhagic fever, Dengue shock syndrome, sickness, infection.http://ijcrr.com/abstract.php?article_id=4435http://ijcrr.com/article_html.php?did=4435

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241146EnglishN2022March15HealthcarePreoperative Ondansetron and Dexamethasone in the Avoidance of Nausea and Vomiting after Cholecystectomy: A randomized controlled trial English110114Maqsood Ahmed SiddiquiEnglish Imran HafeezEnglish Mujeeb Ahmed KhanEnglish Aqil QayoomEnglish Arif Iftikhar MallhiEnglish Ahmed uddin SoomroEnglishEnglishCholecystectomy, Ondansetron, Dexamethasone, Vomiting, Patients, Disordershttp://ijcrr.com/abstract.php?article_id=4436http://ijcrr.com/article_html.php?did=4436