International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
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IJCRR - Vol 04 Issue 05, March, 2012

Pages: 101-107

Date of Publication: 30-Nov--0001


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HOST RESPONSE MODULATION: A MYTH OR REALITY?

Author: Kriti Agarwal, Jaideep Mahendra, Little Mahendra, Jananni .M, Rajeshree.R

Category: Healthcare

Abstract:Periodontitis is a complex microbial disease involving various mechanisms that results in
destruction of connective tissue and bone. Past understanding of etiology and pathogenesis of
periodontal disease focused on the microbial aspect. Based on this the therapeutic efforts were
focused on mechanical or chemotherapeutical removal of bacterial plaque. The plaque biofilm
though considered the prime etiologic factor; it has been just associated with the initiation of
disease. Recent investigations have recognized the crucial role played by host responses involved in the progression & severity of the disease. So therapeutic efforts now is focused on altering (modulating) the host responses. The recent treatment strategy lies in modifying the host responses which will also help in evading the other risk factors like environmental and genetic that can modify the periodontal disease susceptibility. Host Modulation Therapy?s are emerging treatment concept in management of periodontal disease. This review focuses on the present concept of host modulation in comprehensive periodontal management and various chemotherapeutic agents currently applied in Host Modulation Therapy.

Full Text:

INTRODUCTION
Periodontal diseases, which cause the destruction of the supporting structures of the dentition, are common chronic infectious diseases of the oral cavity. They are initiated by Gram negative toothassociated pathogens organized as a biofilm, whose presence elicits a host inflammatory response. Thus, periodontal treatment through the ages has focussed on the reduction of bacterial infection by mechanical removal of plaque and calculus from tooth surfaces i.e. SRP. However, recent research into the pathogenesis of periodontal diseases has led to an important paradigm shift. It is now recognised that the major component of the soft and hard tissue destruction seen in periodontitis occurs as a result of activation of the host?s immuneinflammatory defence mechanisms in response to the presence of bacterial plaque.1 Host-derived pro-inflammatory mediators and cytokines,togetherwith proteolytic enzymes such as matrixmetalloproteinases (MMPs), play a significantrole in the changes in connectivetissue and bone metabolism thatlead to the breakdown of periodontalligament (PDL) and alveolar boneresorption. Host modulatorytherapy (HMT) can be combinedwith traditional periodontal therapiesthat reduce the bacterial burden (e.g.SRP) and also risk factor modification(e.g. smoking cessation therapy) toconstitute a comprehensive treatmentstrategy for periodontitis. Three most important potential approaches to host modulation include: a) inhibition of matrix metalloproteinases (MMPs) with antiproteinases b) blocking production of proinflammatory cytokines and prostaglandins with anti inflammatory drugs and c)inhibition of active osteoclasts with bone sparing agents.2 To date, thereis one approved, systemic therapy that isprescribed as a host response modifier inthe treatment of periodontal disease andthat is adjunctive subantimicrobial dosedoxycycline (SDD) which downregulates theactivity of MMPs.

MATRIX METALLOPROTEINASES (MMPs)
Acting as the prototypical endotoxin, lipopolysaccharides(LPS), amajor component of the outer membraneof Gramnegative bacteria, initiate the cascadeof events leading to periodontal tissue destruction.3 The MMPs comprise a family of zinc dependentproteolytic enzymes. MMPs areprimarily responsible for degrading theextracellular matrix in a variety ofpathological conditions including rheumatoidarthritis, osteoarthritis, autoimmuneulcerative skin lesions and alsotumour cell invasion and metastasis.4MMPsalso play a key role in periodontitis, andare produced by each of the major celltypes found in human periodontal tissuesincluding fibroblasts, keratinocytes,macrophages, PMNs (neutrophils) andendothelial cells.5 They are implicated in a number ofprocesses in normal bone remodeling, including boneresorption and bone formation. MMPs are usedas a biomarker of periodontalseverity and as a response to therapy.

Inhibition of MMPs
Currently, clinical therapy inhibiting the mediatorsof connective tissue breakdown (eg MMP) is used for the adjunctivetreatment of periodontitis. This is accomplishedthrough the non-antimicrobial activities of low-dosetetracycline and tetracycline analogs via the inhibitionof MMP-8 and -13 protease mechanisms.6The tetracyclineanalog doxycycline hyclate, available for usespecifically in periodontal disease, is the only collagenaseinhibitor approved by the United States Foodand Drug Administration (FDA) for any human disease.7A major concern, however,was that the long-term administrationof doxycycline might be associated withthe development of antibiotic resistance.Indeed, when antibiotic doses of tetracycline(250 mg daily for 2–7 years) hadpreviously been given to patients withrefractory periodontitis, up to 77% ofthe patients? cultivable subgingival microfloraexhibited tetracycline resistance.8 In light of thisconcern, a low, subantimicrobial dose of doxycycline (SDD) preparation wasintroduced, containing 20 mg doxycycline,as opposed to the 50 or 100 mgdose that is available for antibioticpurposes.9 SDD (20 mgtwice daily) administered for just 2weeks inhibited collagenase activity by60–80% in the gingival tissues ofpatients with chronic periodontitis.9 Because the low-dose formulationsof these drugs have lost their antimicrobial activity,the therapeutic action witnessed is primarily due tothe modulation of the host response. This subantimicrobial-dose doxycycline (SDD) approach has becomewidely established as an effective adjunctivesystemic therapy in the management of periodontitis,along with the traditional mechanical therapies ofscaling and root planing (SRP).

 

In a recent systematic review,the effectiveness of SRP accompanied by MMP inhibition(by SDD), as an adjunctive treatment, showedimproved outcomes that persisted for 9 months inadults with chronic periodontitis as observed in gainsin clinical attachment level (CAL) and probing depth(PD) reduction.2Recentstudies11, 12 demonstrated the abilityof SDD to be used to maintainbonemass while reducing periodontaldiseaseprogression.In another early clinical study13the efficacy and safety of SDD were evaluated in conjunctionwith SRP in subjects with chronic periodontitis.Here, the more severe the periodontitis, the greaterthe observed attenuation of disease activity by SDD therapy. Although there is strong evidenceto suggest that inhibition ofMMPs in patients with periodontaldisease clearly offers potential indisease management when coupledwith mechanical therapy, suchas SRP, there is only preliminary evidence available to suggest the value of MMP inhibitorytherapies for patients with periimplant diseaseor in those conditions requiring surgical management.2,9

 

It has been shown that SDD (marketed as Periostat) hasno antibacterial activity and does not produce resistantstrains even after months of use. Adverse effects are alsominimal, with a side effect profile similar to placebo.However, like all tetracyclines, there is the potential formultiple drug interactions, particularly with calcium andmagnesium containing preparations. The drug should alsonot be given to patients who are known to be allergic tothe tetracyclines and is to be avoided in pregnancybecause of the risk of tetracycline stain in developingteeth. Currently, SDD is the only drug regimen approvedspecifically for host modulation in the treatment ofperiodontitis. It is not entirely clear how long SDD needsto be used, but the drug can be safely administered for upto 9 months. One protocol for the use of the drug calls for SDD to be prescribed for 3 months at the beginning oftreatment (scaling and root planing) with reevaluation atthe end of the three month trial of the drug. If thepatient has responded well with respect to changes inclinical parameters, the drug can be discontinued. Forthose individuals not responding well to phase 1 therapy,the drug can be continued as additional treatment isrendered.

Bisphosphonates as bone-sparing agents
Bisphosphonate drugs have wellcharacterized modulatoryroles on osteoclast function and bone metabolism.14Notably, at the tissue level, they decreasebone turnover by decreasing bone resorption and byreducing the number of new bone multicellular units.At the cellular level, they decrease osteoclast and osteoblastrecruitment, decrease osteoclast adhesion,and decrease the release of cytokines by macrophages. Based on these properties, severalgenerations of oral bisphosphonate drugs have beensuccessfully developed for the treatment of postmenopausalosteoporosis, osteopenia, and Paget?s diseaseof bone.15Because of these same properties, apossible use for this class of drugs in the managementof periodontal disease was put forth.A few clinical studies have been performed to examinea possible use for bisphosphonates in the managementof periodontal bone loss. In a study15 of 40subjects with chronic periodontitis,a statistically significantdecrease in the proportion of teeth demonstratingbone losswas observed.

ADVERSE EFFECTS WITH BISPHOSPHONATE DOSING
Bisphosphonates are administered by intravenous (IV)infusion (in the case of treatment for metastatic bonecancers) or orally (for the treatment of decreased bonedensity in osteoporosis). Because of a significant rateof non-compliance and the subsequent decrease inclinical efficacy, IV bisphosphonate delivery has beenused extensively for malignant bone diseases, as wellas in breast, prostate, and lung cancer.17However, anumber of publications18,19 documented the retrospectivereports associating IV bisphosphonate delivery andosteonecrosis of the jaws (ONJ).Clinically, ONJis essentially exposed bone in the maxilla or mandiblethat does not healwithin 8 weeksof identification by health careprofessionals (HCPs). Compromised healing was successfully treated withsystemic antibiotics, local microbial mouthrinse, andaggressive defect management via detoxification andamixture of bone graft and tetracycline. 17This suggeststhat dental health care professionals should treat patients undergoinglong-termoral bisphosphonate treatment with caution. Overall, the use of bisphosphonates for the managementof periodontal diseases has limited promise,especially in affecting alveolar bone loss. However,despite their different mode of action, additional studiesare needed to evaluate their potential as alveolarbone–sparing agents.Considerations related tothe duration of use are relevant, given the reportedrisks associated with ONJ related to the long-term useof high-dose bisphosphonates, contrasting the potentialbenefits of the short-term oral use of these drugs.Despite progression in this area of research and a betterunderstanding of the reported risks, a number ofquestions for future consideration of bisphosphonatesin the treatment of periodontal diseases remain, whichshould be addressed.

TREATMENT RECOMMENDATIONS FOR PATIENTS WITH OSTEOPOROSIS RECEIVING BISPHOSPHONATE THERAPY19:

  • Patients informed of risks
  • Oral hygiene and dental care emphasized
  • Not necessary to require dental examination prior to bisphosphonate therapy or alter dental management
  • For patients on bisphosphonates >3 years:

Periodontal disease treatment nonsurgically or conservative surgical therapy Dental-implant placement with informed consent Endodontic treatment preferable to extraction or periapical surgery For invasive procedures, a drug vacation may be helpful but has not been validated

Non steroidal anti inflammatory drugs
Non steroidal anti inflammatory drugs (NSAIDS) have been traditionally utilized in the treatment of pain and acute and chronic inflammation. The antiinflammatory activity of NSAIDS occurs through the inhibition of prostaglandin synthesis. NSAIDS limit the progression of periodontitis through the ability to reduce inflammation and to decrease bone resorption. Several studies have indicated along with SRP, systemically administered NSAIDS like flurbiprofen, naproxen and meclofenamate sodium decrease the rate of alveolar bone loss.

The potential harmful side effects of chronic NSAID therapy include gastrointestinal upset and bleeding. The use of NSAID in periodontitis is still under investigation.

CONCLUSION
There has been a great deal of basic and clinical researchfocusing on the underlying mechanisms ofthe major enzymatic drivers of the aggressive tissuedestruction found in periodontitis. Major drivers of this damage are MMPs and other osteoclastderivedmediators of bone resorption, all of which actas part of the host inflammatory response. Modificationof this host response via the use ofMMPinhibitors,along with the use of bisphosphonates as blockers ofperiodontal tissue destruction, has shown promise inthe therapeutic treatment of these disease states. Althoughquestions remain regarding optimizing treatmentefficacy while limiting any potential adverseeffects, the evidence clearly suggests a strong potentialfor the modulation of the host response in aidingdisease management, when coupled with traditionalmechanical therapy.20

Future approaches
An emerging concept in the study ofinflammation is the idea that inflammation is activelyterminated following an insult rather than just fading away.Resolution of inflammation appears to be promoted byactive mediators designated resolvins and protectins.These specialized molecules are synthesized at the site ofinflammation and help to terminate inflammation and promote regeneration in several ways, includingpromoting removal of cellular debris and reducingrecruitment of neutrophils. Inhibition of inflammatory cytokines through recombinant human IL- 11 is being investigated. The antiinflammatory actions of omega-3 fatty acids havealso been verified for treatment of rheumatoid arthritis(RA). When used to treat RA, omega-3 fatty acids havebeen shown to reduce pain and inflammation and toreduce the need to take other medications such asNSAIDs.

References:

1. Offenbacher S: Periodontal diseases pathogenesis. Annals of Periodontology 1996; 1: 821–878.

2. Reddy MS, Geurs NC, Gunsolley JC: Periodontal host modulation with antiproteinase, anti-inflammatory and bone sparing agents. A systematic review. Annals of Periodontology 2003; 1: 12-37.

3. Kinney JS, Ramseier CA, Giannobile WV: Oral fluid based biomarkers of alveolar bone loss in periodontitis.Ann N Y Acad Sci 2007;1098:230-251.

4. Birkedal-Hansen, H: Role of matrix metalloproteinases in human periodontal diseases. Journal of Periodontology 1993;64: 474–484.

5. Preshaw PM, Hefti AF, Jepsen S, Etienne D, Walker C, Bradshaw H:Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis.A review. J Clin Periodontol 2004; 31: 697–707.

6. Ashley RA: Clinical trials of a matrix metalloproteinase inhibitor in human periodontal disease. SDD Clinical Research Team. Ann N Y Acad Sci 1999; 878:335-346.

7. Sorsa T, Tja¨derhane L, Konttinen YT, et al: Matrix metalloproteinases: Contribution to pathogenesis, diagnosis and treatment of periodontal inflammation.Ann Med 2006; 38:306- 321.

8. Kornman KS, Karl EH: The effect of long-term low-dose tetracycline therapy on the subgingival microflora in refractory adult periodontitis. J of Periodontology 1982; 53: 604–610. 

9. Golub, LM, Ciancio SG, Ramamurthy NS, Leung M, McNamara TF: Lowdose doxycycline therapy: effect on gingival and crevicular fluid collagenase activity in humans. Journal of Periodontal Research 1990; 25: 321– 330.

10. Golub LM, Lee HM, Ryan ME, et al: Tetracyclines inhibit connective tissue breakdown by multiple nonantimicrobial actions. Adv Dent Res 1998; 12: 12-26.

11. Payne JB, Stoner JA, Nummikoski PV, et al: Subantimicrobial dose doxycycline effects on alveolar boneloss in post-menopausal women. J Clin Periodontol 2007; 34:776-787.

12. Reinhardt RA, Stoner JA, Golub LM, et al: Efficacy of sub-antimicrobial dose doxycycline in post-menopausal women: Clinical outcomes. J Clin Periodontol 2007; 34:768-775.

13. Caton JG, Ciancio SG, Blieden TM, et al: Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. J Periodontol 2000;71: 521-532.

14. Tenenbaum HC, Shelemay A, Girard B, Zohar R, Fritz PC.: Bisphosphonates and periodontics: Potential applications for regulation of bone mass in the periodontium and other therapeutic/diagnostic uses. J Periodontol 2002;73:813-822.

15. Kamel HK: Update on osteoporosis management in long-term care: Focus on bisphosphonates. J Am Med Dir Assoc 2007;8:434-440.

16. Jeffcoat MK, Reddy MS : Alveolar bone loss and osteoporosis: Evidence for a common mode of therapy using the bisphosphonate alendronate. In: Davidovitch Z, Norton LA, eds. Biological Mechanisms of Tooth Movement and Craniofacial Adaptation,vol. 1. Cambridge, MA: Harvard Society for the Advancement of Orthodontics; 1996:365-373.

17. Wang HL, Weber D, McCauley LK: Effect of long-term oral bisphosphonates on implant wound healing: Literature review and a case report. J Periodontol 2007; 78:584-594.

18. Ficarra G, Beninati F, Rubino I, et al: Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment. J Clin Periodontol 2005;32: 1123-1128.

19. Khosla S, Burr D, Cauley J, et al: Bisphosphonate associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007; 22:1479-1491.

20. Giannobile WV:Host response therapeutics for periodontal disease. J Periodontol 2008; 79:1592-1600.

Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by situs slot and Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh et al. situs slot "Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma situs slot entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by situs slot et al entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09
Late to bed everyday? You may die early, get depression situs slot
Egg a day tied to lower risk of heart disease situs slot
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List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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