Three decades of advancements in osteoarthritis research: insights from transcriptomic, proteomic, and metabolomic studies.

OBJECTIVE: Osteoarthritis (OA) is a complex disease involving contributions from both local joint tissues and systemic sources. Patient characteristics, encompassing sociodemographic and clinical variables, are intricately linked with OA rendering its understanding challenging. Technological advancements have allowed for a comprehensive analysis of transcripts, proteomes and metabolomes in OA tissues/fluids through omic analyses. The objective of this review is to highlight the advancements achieved by omic studies in enhancing our understanding of OA pathogenesis over the last three decades. DESIGN: We conducted an extensive literature search focusing on transcriptomics, proteomics and metabolomics within the context of OA. Specifically, we explore how these technologies have identified individual transcripts, proteins, and metabolites, as well as distinctive endotype signatures from various body tissues or fluids of OA patients, including insights at the single-cell level, to advance our understanding of this highly complex disease. RESULTS: Omic studies reveal the description of numerous individual molecules and molecular patterns within OA-associated tissues and fluids. This includes the identification of specific cell (sub)types and associated pathways that contribute to disease mechanisms. However, there remains a necessity to further advance these technologies to delineate the spatial organization of cellular subtypes and molecular patterns within OA-afflicted tissues. CONCLUSIONS: Leveraging a multi-omics approach that integrates datasets from diverse molecular detection technologies, combined with patients' clinical and sociodemographic features, and molecular and regulatory networks, holds promise for identifying unique patient endophenotypes. This holistic approach can illuminate the heterogeneity among OA patients and, in turn, facilitate the development of tailored therapeutic interventions.

Evolution and advancements in genomics and epigenomics in OA research: How far we have come.

OBJECTIVE: Osteoarthritis (OA) is the most prevalent musculoskeletal disease affecting articulating joint tissues, resulting in local and systemic changes that contribute to increased pain and reduced function. Diverse technological advancements have culminated in the advent of high throughput "omic" technologies, enabling identification of comprehensive changes in molecular mediators associated with the disease. Amongst these technologies, genomics and epigenomics - including methylomics and miRNomics, have emerged as important tools to aid our biological understanding of disease. DESIGN: In this narrative review, we selected articles discussing advancements and applications of these technologies to OA biology and pathology. We discuss how genomics, deoxyribonucleic acid (DNA) methylomics, and miRNomics have uncovered disease-related molecular markers in the local and systemic tissues or fluids of OA patients. RESULTS: Genomics investigations into the genetic links of OA, including using genome-wide association studies, have evolved to identify 100+ genetic susceptibility markers of OA. Epigenomic investigations of gene methylation status have identified the importance of methylation to OA-related catabolic gene expression. Furthermore, miRNomic studies have identified key microRNA signatures in various tissues and fluids related to OA disease. CONCLUSIONS: Sharing of standardized, well-annotated omic datasets in curated repositories will be key to enhancing statistical power to detect smaller and targetable changes in the biological signatures underlying OA pathogenesis. Additionally, continued technological developments and analysis methods, including using computational molecular and regulatory networks, are likely to facilitate improved detection of disease-relevant targets, in-turn, supporting precision medicine approaches and new treatment strategies for OA.

Social intelligence in health professions educationists: how it helps to deal with challenges at the workplace? a mixed-method study.

Objectives: To identify the social intelligence of medical educationists, and the coping strategies used to deal with workplace challenges. METHODS: The mixed-method study with an explanatory sequential design was conducted from March 15 to July 30, 2021, after approval from the ethics review committee of Riphah International University, Rawalpindi, Pakistan, and comprised medical educationists working in medical and dental colleges and institutions across the country. Data was collected using Tromso social intelligence scale in the quantitative phase. The socially intelligent educationists were identified, and were interviewed. Qualitative data was subjected to thematic analysis to identify predominant themes explaining the coping strategies used. RESULTS: In the quantitative phase, there were 80 participants; 51(63.7%) females and 29(36.3%) males, with 24(30%) having >10 years of professional experience. Of them, 11(13.8%) scored low, 54(67.5%) moderate and 15(18.8%) high on the social intelligence scale. In the qualitative phase, there were 13 subjects; 9(69.2%) females and 4(30.8%) males. There were 4 themes identified as coping strategies; inspire respect and trust, bringing readiness before a change, a collaborative and inclusive approach and use of soft skills. CONCLUSIONS: Variation was seen in the levels of social intelligence among medical educationists working in academic institutions. Those with high levels of social intelligence used their non-cognitive soft skills to manage workplace challenges.

Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.

OBJECTIVE: To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. METHODS: The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27. RESULTS: Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B. CONCLUSIONS: Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration. Clinical Trial Number: Iranian Registry of Clinical Trials: IRCT20221207056738N1.

Assessment of cardiac parameters after the administration of nicorandil before primary percutaneous coronary intervention.

Objective: To assess cardiac troponin I and creatine kinase-myocardial band levels, electrocardiogram changes and major adverse cardiac events after treatment with nicorandil before primary percutaneous coronary intervention. METHODS: The comparative, analytical study was conducted from October to November 2022 at the Pharmacology Department of Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Rawalpindi Institute of Cardiology, Rawalpindi. The sample comprised ST-elevated myocardial infarction patients of either gender aged at least 30 years with an ejection fraction of at least 35% undergoing primary percutaneous coronary intervention. Participants were selected based on the above-mentioned inclusion and informed consent was taken before their enrolment in this research study. The sample was randomised into control group A receiving conventional acute coronary syndrome treatment, and intervention group B receiving nicorandil in addition to the conventional treatment. Cardiac troponin I and creatine kinase-myocardial band levels, electrocardiogram changes, and major adverse cardiac events noted and compared. Data was analysed using SPSS 26. RESULTS: Of the 140 patients, 70(50%) were in each of the 2 groups. In group B, 60(85.7%) patients achieved a completely settled ST segment on electrocardiogram compared to 25(35.7%) in group A (p=0.001). There was a significant inter-group difference with respect to cardiac troponin I value 6 hours after percutaneous coronary intervention and major adverse cardiac events (p<0.05), but creatine kinase-myocardial band level was no significantly different between the groups (p=0.761). Conclusion: Prophylactic use of nicorandil in ST-elevated myocardial infarction patients decreased the incidence of reperfusion injury.

Early initiation of Dapagliflozin and its effect on health related quality of life in acute heart failure: a randomised controlled trial.

OBJECTIVE: To determine the role of dapagliflozin in improving functional status and health-related quality of life in acute heart failure cases. METHODS: The prospective, randomised controlled study was conducted from July 2022 to January 2023 at the Pharmacology Department of Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Armed Forces Institute of Cardiology, Rawalpindi, and comprised hospitalised adult patients of either gender with acute heart failure. They were randomised into two equal groups, with intervention group A receiving oral dapagliflozin 10mg daily in addition to conventional therapy, and with control group B receiving conventional therapy alone. Health-related quality of life was assessed using Kansas City Cardiomyopathy Questionnaire. Improvement in functional status was assessed by New York Heart Association functional classification. Data was obtained at baseline and after 12-week follow-up. Data was compared using SPSS 26. RESULTS: Of the 150 patients, 75(50%) were group A; 62(82.66%) males and 13(17.3%) females with mean age 63.76±10.05 years. There were 75(50%) patients in group B; 60(80%) males and 15(20%) females with mean age 66.13±11.73 years (p>0.05). The study was completed by 73(97.3%) in group A and 69(92%) in group B. The Kansas City Cardiomyopathy Questionnaire scores improved post-intervention compared to baseline values (p<0.001) in both groups. Group A showed comparatively greater improvement in health status compared to group B (p<0.05). CONCLUSIONS: Early initiation of dapagliflozin in patients admitted with acute heart failure was found to be associated with rapid and significant improvement in health and functional status. Clinical Trial Link: https://www.irct.ir. RCT No. (IRCT20220529055013N).

Validation Of An Assessment Tool For Professionalism In Medical Students: A Mixed Method Study.

Objectives: To develop and validate a tool for the assessment of professionalism in medical students during clerkship. METHODS: The mixed-method study was conducted from February to September 2018 at the Islamic International Medical College, Riphah University, Islamabad, Pakistan. A preliminary focus group discussion was followed by two rounds of Delphi technique to validate micro-scenarios for the relevance of each item of the instrument alongside its content validity. For content and construct validation of the tool, content validity, cognitive validity, cognitive pretesting, confirmatory factor analysis and reliability assessment was done. Piloting was done on medical students doing clerkship. Data was analysed using SPSS 21 and AMOS 21. RESULTS: A 35-item preliminary tool from micro-scenarios generated after focus group discussion was developed for the first Delphi round. For the second round, a 29-item tool was resent to the experts for validation. After the second round, the content validity scale was 0.94. Removal of 1 item produced a 28-item tool. Pre-cognitive testing of the 28 items resulted in rephrasing of 4, modification of 2, and deletion of 1 and a tool with 27 items. Piloting was carried out and after CFA resulted in a reduced 21 item tool. Cronbach's alpha value was 0.96. A good to excellent model fit was produced after performing confirmatory factor analysis. CONCLUSIONS: A tool comprising of 21 items scored on a 5-point Likert scale that had acceptable construct validity and good content validity was developed. It can be used to evaluate the level of professionalism of local medical students doing clerkship.

Cardio protective effect of nicorandil in reperfusion injury among patients undergoing primary percutaneous coronary intervention.

Objectives: To evaluate the effect of nicorandil in prevention of reperfusion injury during primary percutaneous coronary intervention by thrombolysis in myocardial infarction flow grade scoring. Methods: A total of 140 patients from Rawalpindi Institute of Cardiology were enrolled in this study conducted from 7th September to 10th of October 2021. These participants were allocated into two major groups. Control group received conventional acute coronary syndrome protocol regimen only whereas experimental group was given nicorandil along with conventional acute coronary syndrome protocol. During primary percutaneous coronary intervention, thrombolysis in myocardial infarction flow grade scoring was analyzed and compared. Results: Majority of participants in nicorandil group achieved thrombolysis in myocardial infarction Grade-3 scoring which indicated reduced rate of no reflow phenomenon as compared to control group. A statistically significant difference was noted in score of both groups (p value = 0.001) signifying prophylactic use of nicorandil before primary percutaneous coronary intervention along with conventional acute coronary syndrome protocol is superior to only conventional acute coronary syndrome protocol regimen to cases in the control group. Conclusion: Use of nicorandil in ST elevated myocardial infarction patients before primary percutaneous coronary intervention prevents reperfusion injury thus decreasing the risk of post percutaneous coronary intervention complications and reducing mortality rate in cardiac patients suggesting its significant cardio protective role.

The effect of Dapagliflozin on renal functions in hospitalized patients with Acute Heart Failure.

Objective: To evaluate the influence of dapagliflozin on renal functions and diuretics use in patients with acute heart failure (AHF). Methods: This comparative analytical study was conducted at Armed Forces Institute of Cardiology, Rawalpindi from July 2022 to November 2022. Patients were distributed equally in two groups i.e. Dapagliflozin and Conventional Groups, where patients received dapagliflozin added to conventional therapy for AHF and, only conventional therapy for AHF respectively. Estimated glomerular filtration rate (eGFR), serum creatinine were measured and compared on admission, after 48 hours and on discharge. Weight loss during hospitalization, daily dose of furosemide and length of hospital stay was also recorded. Quantitative parameters were analyzed using t-test or Mann Whitney U test accordingly. Results: There were no significant baseline differences in renal functions. A modest decline in eGFR was observed in both groups after 48 hours. However, the variation in values of eGFR remained similar among both groups after 48 hours (p-value 0.365) and on discharge (p-value 0.768). Whereas, patients subjected to dapagliflozin treatment exhibited a more profound diuretic response expressed as greater weight loss (p-value < 0.001), achieved at comparatively lower doses of loop diuretics. Moreover, they also had a shorter duration of hospital stay (six vs eight days, p-value <0.001). Conclusion: Institution of dapagliflozin did not cause any significant deterioration of renal functions, whereas; it was associated with improved diuretic response as depicted by more pronounced weight loss at comparatively lower doses of loop diuretics.

Granisetron versus Ondansetron: Comparison of 5HT3 antagonists in preventing spinal anaesthesia induced hemodynamic instability in obstetric patients.

Objectives: To evaluate and compare the Ondansetron and Granisetron in preventing spinal anaesthesia induced hemodynamic instability in obstetric patients. Methods: The comparative analytical study was conducted at Combined Military Hospital, Rawalpindi, from September to October, 2021. One hundred and twenty pregnant women undergoing cesarean section, were enrolled in the study via non probability convenience sampling, and divided into three groups containing 40 participants each based on the type of antiemetic premedication they received, if any: Group N were those not requiring antiemetic premedication, Group O consisted of those given ondansetron 4mg, and Group G had those receiving 3mg granisetron, 15 minutes prior to administration of spinal anaesthesia. Systolic blood pressures and heart rates were recorded before and at multiple intervals after spinal anaesthesia was administered. Episodes of hypotension and bradycardia were recorded. Requirement of phenylephrine and atropine as rescue drugs was recorded for each participant. Results: There was a statistically significant difference in incidence of hypotension among the three groups (p value <0.001), with both drugs being superior to the control group (p value <0.001 for both), and 3mg granisetron being superior to 4mg ondansetron (p value <0.001). As for incidence of bradycardia, ondansetron and granisetron were superior to control group (p value 0.03 and <0.001 respectively), but there was no significant difference between the two drug groups (p value 0.094). Conclusion: High dose granisetron (3mg) is superior to low dose ondansetron (4mg) in preventing hemodynamic fluctuations induced by spinal anaesthesia.

Association between intestinal helminthic infections and anaemia status in preschool children in the district Skardu of Pakistan.

OBJECTIVE: To evaluate the frequency of parasitic infections and to assess the relation between intestinal helminth infection and the anaemia status of pre-school children. METHODS: The community-based cross-sectional study was conducted in Skardu, Pakistan, from August 2016 to January 2017, and comprised pre-school children of either gender. Demographical data was collected using a structured questionnaire. Stool samples were collected and examined for the presence and differentiation of ova / larvae of different intestinal helminths under microscope at the pathology department of a local healthcare facility. Blood haemoglobin was measured from blood samples and anaemia was defined as blood Hb <11g/dL. Data was analysed using SPSS 22. RESULTS: Of the 300 paediatric subjects, 169 (56.3%) were males and 131 (43.7%) females. The overall mean age of the sample was 36±16 months. Of the total, 161(53.67%) were found infected. Among the infected, 93(31%) were males and 68(22.67%) were females (p=0.10). Among those who were infection-free, 46(15.3%) children were anaemic. CONCLUSIONS: Prevalence of helminthic infections in pre-school children in Skardu was found to be high. The public health problem needs to be addressed for the healthy development of children.

Stigma, Opioids, and Public Health Messaging: The Need to Disentangle Behavior From Identity.

Stigma plays an important role in understanding successful interventions to control the opioid epidemic in the United States. Stigma has been described both as an agent to incentivize positive health behavior and as an agent of marginalization contributing to poorer health. Past scholarship has argued that stigma has positively motivated public health changes, for example, among tobacco users; it has also been associated with discrimination against vulnerable individuals, resulting in increasingly poorer health behaviors, for example in relation to HIV-prevention messaging.The discourse on stigma may conflate the denormalization of unhealthy behaviors with wholesale rejection of individual identities. More effective interventions would counter stigma against people who use opioids in general and specifically denormalize opioid misuse. These interventions might alter the effect of public health messaging and ultimately improve outcomes.We argue that public health educators and communication campaigns can contribute to positive social norm change and motivate healthy behaviors by incorporating strategies that attempt to disentangle unhealthy behaviors from identity.

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints.

OBJECTIVES: We recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration. METHODS: We used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression. RESULTS: miR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects. CONCLUSIONS: Our data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA.

Practice to preach self-regulation: Use of metacognitive strategies by medical teachers in their learning practices.

OBJECTIVE: To explore use of metacognitive skills by medical teachers in relation to Zimmerman's model of self-regulation. METHODS: A qualitative phenomenological study was conducted at Riphah International University from February 2017 to August 2017. A semi structured interview of ten medical teachers was planned to uncover the lived experiences of selected teachers to demonstrate how these teachers use metacognitive strategies in different phases of learning. Data was collected by asking five open ended questions after expert validation. Data was analyzed by using N-Vivo software. RESULTS: Total eight themes were extracted. For prediction and planning three themes, brainstorming, making concept map and sufficient time required were isolated while teachers selected learning objectives and level of students for resource selection while for motivation theme selected was previous experience. Two themes, self- questioning to improve the learning and extra effort required to meet the timeline were isolated for monitoring and reflection during and after learning for evaluation of learning process. CONCLUSION: During forethought phase, medical teachers predict their learning process through learning objectives and plan after brainstorming to make a concept map and use suitable learning resources. During learning, they monitor learning process through self-questioning and put extra-effort to meet the deadlines. During and after learning, teachers reflect on their performance.

Evaluating the design and reporting of pragmatic trials in osteoarthritis research.

Objectives: Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. Methods: We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic-explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. Results: None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Conclusion: Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care.

Cultural Factors Influencing Osteoarthritis Care in Asian Communities: A Review of the Evidence.

With the prevalence of osteoarthritis (OA) increasing internationally, there is a need to study the impact of this disease on culturally diverse populations. Individuals of Asian descent make up more than 60% of the world population, yet comprehensive information on the cultural factors that impact OA care is not available. Scoping review methodology using directed content analysis was employed to identify and analyze existing research on OA care for Asians. A categorization matrix was developed using the six care areas from the OA clinical practice guidelines along with an additional three non-clinical areas (cross-cultural adaptation of clinical tools; psychological well-being; family systems and informal care) identified in an initial scan resulting in a total of nine OA care areas to guide initial coding. A full scoping review was conducted across five databases resulting in 656 abstracts screened. All text was coded using the categorization matrix and resulting subthemes were identified. A total of 74 articles were analyzed with 23 subthemes identified across the nine categories. Four new perspectives emerged to support OA care for Asian populations: (1) the importance of family and peer assistance, (2) the importance of culturally specific activities, (3) distrust in western medicine, and (4) impact of positive coping mechanisms on health appraisals. While Asians are more susceptible to knee and hand OA because of their cultural lifestyle factors (e.g. squatting for chores, hygiene and religious activities), and traditional beliefs on OA management (e.g. traditional diet, topical oils, physical therapy), many do not present themselves for conventional treatments (e.g. surgery) until all traditional treatments are exhausted. The results suggest that cultural factors influence the uptake of OA management practices among Asians. Greater awareness of these cultural factors may improve diagnosis, treatment, and management of OA among Asian patients.

Mini Review - Analysis of Artemether and Dihydroartemisinin by high performance high liquid chromatography in biological fluids-issues and solutions.

Artemether-Lumefantrine is the most widely recommended antimalarial combination used to treat millions of patients suffering from malaria. Artemether undergoes rapid metabolism and gets converted to its active metabolite dihydroartemisisn. Drug analysis is a vital aspect to evaluate drugs in research. There are a number of methods available for the determination of artemether in biological fluids. These methods include HPLC based UV detection, GS-MS, HPLC-ECD and HPLC-MS/MS. This article reviews different methods for the determination of artemether in the biological fluids. Among the available methods HPLC-MS/MS proves to be the most accurate and reliable one for analysis. This has the advantage of improved sensitivity and selectivity with smaller sample volume.

Impact of Combined modular assessment on deep learning and personal development of medical students.

OBJECTIVE: To determine the effect of transition of summative assessment from frequent modular to combined block assessment and its role on learning of medical students. METHODS: A descriptive study was carried out at Islamic International Medical College. A questionnaire comprizing of 8 questions with Likert scale (1-5) was designed for 3(rd) year students. The questions were grouped in three categories which included learning acquired, personal development and efficacy of assessment tools used in combined block assessment and frequent modular exam separately. Results of end of year exams were analyzed for difference in performance of students in two exams. The received data was analyzed by using SPPS 21. RESULTS: About 60% students agreed that they need to study regularly in frequent modular exams. Combined block assessment promoted more indepth studies and multiple revisions 51% and 55% students respectively. About 42% students, in comparison with 33%, agreed that CBA helped in their personal development while 42% students agreed to assessment tools used in CBA while only 28% students to those used in frequent modular exam. About 47% students agreed that assessment tools in CBA were useful for deep learning and 47% students agreed that time given in CBA was enough in exam preparation. Comparison of all results (x 2 tests) was statistically significant. The comparison of end of year performance showed improvement in the mean of total marks obtained and decrease in the number of failed students in combined block assessment. CONCLUSION: Transition from frequent to combined block assessment with regular formative assessment has positive effect on learning, personal grooming and performance in summative assessment.

CoagVDb: a comprehensive database for coagulation factors and their associated SAPs.

The current state of the art in medical genetics is to identify and classify the functional (deleterious) or non-functional (neutral) single amino acid substitutions (SAPs), also known as non-synonymous SNPs (nsSNPs). The primary goal is to elucidate the mechanisms through which functional SAPs exert their effects, and ultimately interrogating this information for association with complex phenotypes. This work focuses on coagulation factors involved in the coagulation cascade pathway which plays a vital role in the maintenance of homeostasis in the human system. We developed an integrated coagulation variation database, CoagVDb, which makes use of the biological information from various public databases such as NCBI, OMIM, UniProt, PDB and SAPs (rsIDs/variant). CoagVDb enriched with computational prediction scores classify SAPs as either deleterious or tolerated. Also, various other properties are incorporated such as amino acid composition, secondary structure elements, solvent accessibility, ordered/disordered regions, conservation, and the presence of disulfide bonds. This specialized database provides integration of various prediction scores from different computational methods along with gene, protein, and disease information. We hope our database will act as a useful reference resource for hematologists to reveal protein structure-function relationship and disease genotype-phenotype correlation.

Synergistic Effect of Coenzyme Q10 and L-Carnitine on Gliosis and Anhedonia, in a Rat Model of Multiple Sclerosis: An Immunohistochemical Study.

Objective: This study provides histological evidence of the combined effects of L-Carnitine, and Coenzyme Q10 on gliosis and anhedonia in a rat model of multiple sclerosis (MS). Methods: Fifty male Sprague Dawley rats were randomly divided into 5 groups of 10 rats each. Group 1 was the control group. The rest of the groups were disease models and were given 0.2% cuprizone w/w to induce MS. After 4 weeks, Group 3 started receiving L-Carnitine, Group 4 was given Coenzyme Q10, and Group 5 received both, while cuprizone poisoning continued. After 12 weeks sucrose preference test and tail suspension test were performed for anhedonia. Rats were euthanized and brains were dissected, and assessed for astrocytes, oligodendrocytes, and microglial count. Results: A significant increase in oligodendrocyte count, while a reduction in astrocyte and microglial count was seen in the synergistic group (p < 0.05). Synergism could not be proved in anhedonia. Conclusion: The combination of Coenzyme Q10 and L-Carnitine has a synergistic effect in controlling gliosis in a rat model of MS, but synergism could not be demonstrated on anhedonia.