Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study.

The present prospective cohort study evaluated the prevalence of FSH-R receptor Asn680Ser and Ala307Thr among infertile Indian women and the correlation of these polymorphisms with ART outcomes. Total 804 infertile and 209 fertile controls were enrolled for FSH-R analysis. Correlation of different genotypes with ovarian reserve markers, IVF parameters, and cumulative live birth rates (CLBR) was done among women undergoing IVF. In fertile controls, at 680 position GG (Ser/Ser) was the most common genotype; but among infertile women, all the genotypes were equally distributed. There was no significant difference in ovarian response parameters, oocyte yield, and CLBR among the three genotype groups. Empty follicle syndrome (EFS) was highest in women with AA or AG type at both positions. On categorisation of unexpected poor responders according to POSEIDON stratification; GG genotype at both positions had the lowest risk ratio of low-oocyte yield in ART cycles, but these differences were not statistically significant. This is the largest study from Indian ethnicity showing GG (Ser/Ser) genotype is most common among fertile women. The effect of FSH-R genotypes is very marginal on IVF parameters and is not reflected in CLBR. More prospective data may be required on the correlation of these genotypes with genuine EFS, thus stratifying the next cycles with self or donor oocytes. Routine genetic testing of FSH-R polymorphism should not be done except in a research setting. As both 680 and 307 positions are in linkage disequilibrium, only 680 position analysis may be done in a research setting.

British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease.

Sjögren disease (SD) is a chronic, autoimmune disease of unknown aetiology with significant impact on quality of life. Although dryness (sicca) of the eyes and mouth are the classically described features, dryness of other mucosal surfaces and systemic manifestations are common. The key management aim should be to empower the individual to manage their condition-conserving, replacing and stimulating secretions; and preventing damage and suppressing systemic disease activity. This guideline builds on and widens the recommendations developed for the first guideline published in 2017. We have included advice on the management of children and adolescents where appropriate to provide a comprehensive guideline for UK-based rheumatology teams.

Total Antioxidant Status and Oxidative Stress in Patients with COVID-19 Infection.

INTRODUCTION: Oxidative stress (OS) may have a role in the pathogenesis and severity of the coronavirus disease 2019 (COVID-19) disease. The present study was conducted to estimate the association of inflammatory markers, total antioxidant status (TAS), and malondialdehyde (MDA) levels with the severity of the disease and to identify their trends after recovery. MATERIALS AND METHODS: Adult patients admitted with moderate or severe COVID-19 were included after obtaining written informed consent from patient or next of kin. Patients who were critically ill, on ventilator, or in sepsis/septic shock were excluded. Levels of inflammatory markers, TAS, and OS as measured by MDA were estimated within 24 hours of admission and reevaluated at 12 weeks following discharge. RESULTS: The mean age of the 40 patients (42.5% females) was 55 ± 15 years. TAS values (in trolox equivalents/L) were significantly reduced in severe compared to moderate COVID-19 patients at admission (7.2 ± 4.19 vs 12.3 ± 5.21). These increased at 12 weeks after discharge. The MDA levels (in nmol/mL) were significantly higher in severe in comparison to moderate disease (7.1 ± 2.68 vs 4.1 ± 1.81). These values showed a downward trend 12 weeks after discharge in severe disease group. Admission levels of interleukin-6 (IL-6), D-dimer, and lactate dehydrogenase (LDH) were statistically higher in severe COVID-19 patients in contrast to moderate disease. CONCLUSION: Moderate and severe COVID-19 are associated with a state of high OS and a low total antioxidant levels which tend to recover at 3 months following discharge.

Prevalence of dementia in India: National and state estimates from a nationwide study.

INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.

The Long and Short of Summative Assessment in Competency Based Medical Education: Time to Raise the Bar?

BACKGROUND: The Competency-based medical education (CBME) has been introduced for MBBS programme in India from 2019. Reorganization of the assessment system is required to meet the challenges imposed by this new framework. OBJECTIVES: An evaluation of the university summative assessments held prior to the introduction of CBME-based curriculum was carried out to analyze the pattern, relevance and distribution of questions. METHODS: Five sets of annual and supplementary summative examination papers from three universities, State (SU), Private (PU) and Medical (MU) were evaluated. The analysis included format i.e. Structured and Modified Essay questions, Short notes, other formats; marks distribution; terminology-based level of cognitive domain; subject-based relevance and topic-based distribution of questions. RESULTS: A total of 352 questions were analyzed. The maximum number of questions were from the state university (140, 39.7%).The contribution of short notes in the theory papers was 65.8% (PU), 87.1% (SU) and 88.9% (MU).Only the PU had Modified-Essay Questions (10.5%) and Modified short notes(4.7%). Terminology addressing higher cognitive domains was low as the questions assessed mainly the knowledge level (80-96.8%), comprehension 3.1%-6.4%. Only the PU had problem solving questions comprising 11.7% of total questions. Majority of questions had moderate or high relevance and only 2.1%-8.2% were of low-relevance. Inter-university differences in the topics were observed for dermatology, psychiatry, and infections. CONCLUSIONS: The present evaluation of high-stakes assessment in three universities indicates minor differences in the format of questions. Questions were predominantly in the form of short notes, structured essays and modified essays were a rarity; few questions targeted higher cognitive levels although majority had high-moderate relevance.

Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles - randomized controlled trial.

PURPOSE: To evaluate the benefits of myoinositol plus metformin versus myoinositol alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction cycles. MATERIALS AND METHODS: Total 116 infertile PCOS women were randomized: Group I (n = 57): metformin (1500 mg) plus myoinositol (4 g) per day; Group II (n=59): myoinositol 4 g per day. Subjects were advised to try for spontaneous conception. Those who did not conceive after three months were given three cycles of ovulation induction. Primary outcome was clinical pregnancy rate after 6 months. Secondary outcomes were improvement in metabolic and endocrine parameters, ongoing pregnancy, abortion and multiple pregnancy rate. RESULTS: Baseline demographic, metabolic and hormonal parameters were comparable in two groups. After 3 months of therapy, both study groups had comparable improvement in metabolic and hormonal parameters. After 6 months, clinical pregnancy rate was 42.0% in Group I and 45.5% Group II respectively (RR 0.92(95% CI:0.60-1.43) (p > .05). Side-effects (mainly gastrointestinal) were significantly higher in Group I than group II. CONCLUSIONS: Myoinositol (4 g) might be used alone as an insulin sensitizer to improve metabolic, hormonal and reproductive outcome in infertile PCOS women. Further studies with large numbers are warranted to confirm the role of myoinostiol as a sole insulin sensitizer.

Short-term outcome of local pancreatic complications in a public hospital from North India.

INTRODUCTION: Dearth in the literature pertaining to natural history of acute pancreatitis (AP) necessitates further studies to evaluate the outcome of local pancreatic complications using the revised Atlanta classification. OBJECTIVE: To evaluate the outcomes of local pancreatic complications after first episode of AP, risk factors for their development and predictors of need for intervention. METHODOLOGY: A prospective study was carried out on 50 consecutive cases of AP who developed local pancreatic complications from January 2015 to July 2016. After imaging, they were categorised into acute pancreatic fluid collection (APFC) and acute necrotic collection (ANC). The risk factors for their development and the need for intervention were assessed. RESULTS: Of 50 patients, 20 developed APFC and 30 ANC. Of ANC cases, 27 progressed into walled-off necrosis (WON), of which 4 were managed conservatively and 18 collections were drained percutaneously, 3 underwent endotherapy (transmural drainage and endoscopic necrosectomy) and 2 died following percutaneous drainage (PCD) and surgery. Ten WON collections persisted at the end of 3rd month. Collections resolved in 6 of 20 APFC patients, 14 formed pseudocysts, of which 10 showed resolution with or without intervention and only 4 of them persisted at the end of study. Size of collection ≥6 cm was independent predictor of intervention irrespective of type of collections while in cases of ANC, extensive necrosis (>30%) and multiple collections were more likely to require intervention. CONCLUSION: Incidence of ANC is more common than APFC when local pancreatic fluid collections develop most of which develop WON and require intervention.

Pregnancy with Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder characterized by the presence of vascular naevi, varicose veins and soft tissue or bone hypertrophy affecting one or more extremities. Due to the rarity of the syndrome, there is limited literature regarding the current practice in the management of pregnancy complicated with KTS. Successful management of pregnancy with KTS is a challenge for clinicians as pregnancy exacerbates the already increased risk of thrombosis and haemorrhage associated with this syndrome. We report a patient with KTS with previous poor obstetric history managed with favourable maternal and foetal outcomes.

Flies Without Borders: Lessons from Chennai on improving India's municipal public health services.

India's cities face key challenges to improving public health outcomes. First, unequally distributed public resources create insanitary conditions, especially in slums - threatening everyone's health, as suggested by poor child growth even amongst the wealthiest. Second, devolving services to elected bodies works poorly for highly technical services like public health. Third, services are highly fragmented. This paper examines the differences in the organisation and management of municipal services in Chennai and Delhi, two cities with sharply contrasting health indicators. Chennai mitigates these challenges by retaining professional management of service delivery and actively serving vulnerable populations - while services in Delhi are quite constrained. Management and institutional issues have received inadequate attention in the public health literature on developing countries, and the policy lessons from Chennai have wide relevance.

T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation.

The follicular helper T cell (TFH) are established regulators of germinal center (GC) B cells, whether TFH have pathogenic potential independent of B cells is unknown. Based on in vitro TFH cell differentiation, in vivo T cell transfer animal colitis model, and intestinal tissues of inflammatory bowel disease (IBD) patients, TFH and its functions in colitis development were analyzed by FACS, ChIP, ChIP-sequencing, WB, ELISA and PCR. Herein we demonstrate that intestinal tissues of patients and colon tissues obtained from Rag1-/- recipients of naïve CD4+ T cells with colitis, each over-express TFH-associated gene products. Adoptive transfer of naïve Bcl6-/- CD4+ T cells into Rag1-/- recipient mice abrogated development of colitis and limited TFH differentiation in vivo, demonstrating a mechanistic link. In contrast, T cell deficiency of interferon regulatory factor 8 (IRF8) resulted in augmentation of TFH induction in vitro and in vivo. Functional studies showed that adoptive transfer of IRF8 deficient CD4+ T cells into Rag1-/- recipients exacerbated colitis development associated with increased gut TFH-related gene expression, while Irf8-/-/Bcl6-/- CD4+ T cells abrogated colitis, together indicating that IRF8-regulated TFH can directly cause colon inflammation. Molecular analyses revealed that IRF8 suppresses TFH differentiation by inhibiting transcription and transactivation of the TF IRF4, which is also known to be essential for TFH induction. Our documentation showed that IRF8-regulated TFH can function as B-cell-independent, pathogenic, mediators of colitis suggests that targeting TFH could be effective for treatment of IBD.

Correlation of body mass index (BMI), anti-mullerian hormone (AMH), and insulin resistance among different polycystic ovary syndrome (PCOS) phenotypes - a cross-sectional study.

One hundred and fifty infertile polycystic ovary syndrome (PCOS) women were classified into four phenotypes on the basis of Rotterdam criteria. Homeostatic model assessment of insulin resistance (HOMA-IR) with a cutoff ≥2.5 was considered as a measure of insulin resistance (IR). Maximum number of patients, 57 (38%) in our cohort belonged to phenotype A or the classical phenotype with all 3 features of Rotterdam criteria. Mean body mass index (BMI) in all phenotypes was more than 25 kg/m2 and the highest was seen in phenotype B. According to BMI categories in the four phenotypes, more number of women was in the obese category in phenotype A (24.5%) and B (56.5%) in comparison to phenotype C (18.2%) and D (10.8%) (p<.001). There was no difference in median HOMA-IR among different phenotype categories (p=.718). The median value of anti-mullerian hormone (AMH) was highest in phenotype A (11.68 ng/ml [7.94-16.46]) and significantly more in comparison to B phenotype (Kruskal-Wallis, p=.018). Thus there is heterogeneity in AMH levels and BMI in different PCOS phenotypes with higher levels in the most severe phenotypes. There is, however, no correlation of IR among the different phenotype groups and further investigation is needed to characterize its role in phenotypic classification.

Fertility awareness and knowledge among Indian women attending an infertility clinic: a cross-sectional study.

BACKGROUND: To evaluate fertility knowledge and awareness among infertile women attending an Indian assisted fertility clinic and their understanding of the menstrual cycle, how age affects fertility and need for assisted fertility treatment. METHODS: A cross sectional study was conducted including 205 women seeking fertility treatment at an assisted reproductive unit between March 2017 to August 2017. Patients were interviewed with the help of structured questionnaire by a fertility counsellor. The previous studies were reviewed and a questionnaire was made according to our patient profile and sociodemographic characteristics. Knowledge and awareness was stratified according to socioeconomic status (SES). RESULTS: Most women (59%) were aged between 20 to 30 years indicating concern about their fertility and need for evaluation. More than half (63%) women were from the middle socio-economic strata. Knowledge about fertility and reproduction was low: 85% were not aware of the ovulatory period in the menstrual cycle, only 8% considered age more than 35 years as the most significant risk factor for infertility and most were unaware of when to seek treatment for infertility after trying for pregnancy. Less than half of women understood the need for assisted fertility treatment and donor oocytes in advanced age. CONCLUSIONS: Most Indian women across different SES are unaware of the effect of age on fertility. Targeted educational interventions are needed to improve knowledge regarding ideal age of fertility, factors affecting fertility potential and fertility options available for sub-fertile couples. Fertility counselling and information should be provided to young people at every contact with health care professionals.

Useful information provided by graphic displays of automated cell counter in hematological malignancies.

BACKGROUND: Automated cell counters have become more and more sophisticated with passing years. The numerical and graphic data both provide useful clues for suspecting a diagnosis especially when the workload is very high. AIM: We present our experience of useful information provided by graphic displays of an automated cell counter in hematological malignancies in a cancer hospital where a large number of complete blood count (CBC) requests are received either before or during chemotherapy. This study was conducted to assess the usefulness of hematology cell counter, viz. WBC-Diff (WBC differential), WBC/BASO (WBC basophil) and IMI (immature myeloid information) channel scatter plots, and the flaggings generated in various hematological malignancies. MATERIAL & METHODS: The graphic displays have been compiled over a period of 1 year (October 2015-September 2016) from blood samples of various solid and hematological malignancies (approximately 400 per day) received for routine CBC in the laboratory. Approximately 50 000 scattergrams have been analyzed during the study period. The findings were confirmed by peripheral blood smear examination. RESULTS: The scattergram analysis on XE-2100 is very sensitive as well as specific for diagnosing acute leukemia, viz. acute myeloid leukemia, acute lymphoblastic leukemia; chronic myeloproliferative disorders, viz. chronic myeloid leukemia; and chronic lymphoproliferative disorder especially chronic lymphocytic leukemia. CONCLUSION: It is suggested that the laboratories using the hematology analyzers be aware of graphic display patterns in addition to flaggings generated which provide additional information and give clue toward the diagnosis even before peripheral smear examination.

The Educational Environment of the Indian Undergraduate Medical Students: Is it Good Enough?

Background: The educational environment (EE) is a crucial determinant of successful outcomes in an undergraduate (UG) medical education programme. The present study utilized the Dundee Ready Education Environment Measure (DREEM) which is a validated tool for this assessment in medical schools. Aims and Objectives: a. To explore the perceptions of undergraduate medical students of their learning environment b. To identify both strengths and weaknesses in students' educational environment c. To suggest remedial measures to overcome the deficiencies Methodology: The present cross-sectional, questionnaire-based study was conducted in the Academic year 2015. A printed form of the validated inventory DREEM, was distributed among undergraduate students of second, fourth, sixth and eighth semester, maintaining anonymity of the respondents. The mean item scores, domain scores and global scores were calculated and the results were analyzed using SPSS Version 15 and one-way ANOVA. Results: The composite overall perception of EE i.e. DREEM score for the Medical College was 118.4±16.9, indicating that the perception was positive. The fourth and sixth semester rating were lower at 115.90±3.76 and 106.10± 3.46, respectively while the second and eight semester students rated it higher at 123.13±5.03 and 127.05± 3.95, respectively. This difference was statistically significant. The highest rated items were knowledgeable teachers, having good friends, and a pleasant accommodation. The most problematic items were a poor support system for stressed students, inability to memorize everything, and over-emphasis on factual learning. Students also perceived the teachers to be authoritarian. They observed that the teaching was teacher-centric, burdensome and boring. Conclusion: This study helped us to introspect and identify remediable areas in the EE of our medical college with special emphasis on a student-centered curriculum focusing on the national needs as well as student interest. Teachers need to change their approach to teaching-learning environment by introducing changes in their teaching methodology, assessment methods and interaction with students.

Physical activity but not sedentary activity is reduced in primary Sjögren's syndrome.

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren's syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.

Combined Bioinformatic and Rational Design Approach To Develop Antimicrobial Peptides against Mycobacterium tuberculosis.

Drug-resistant pathogens are a growing problem, and novel strategies are needed to combat this threat. Among the most significant of these resistant pathogens is Mycobacterium tuberculosis, which is an unusually difficult microbial target due to its complex membrane. Here, we design peptides for specific activity against M. tuberculosis using a combination of "database filtering" bioinformatics, protein engineering, and de novo design. Several variants of these peptides are structurally characterized to validate the design process. The designed peptides exhibit potent activity (MIC values as low as 4 µM) against M. tuberculosis and also exhibit broad activity against a host of other clinically relevant pathogenic bacteria such as Gram-positive bacteria (Streptococcus) and Gram-negative bacteria (Escherichia coli). They also display excellent selectivity, with low cytotoxicity against cultured macrophages and lung epithelial cells. These first-generation antimicrobial peptides serve as a platform for the design of antibiotics and for investigating structure-activity relationships in the context of the M. tuberculosis membrane. The antimicrobial peptide design strategy is expected to be generalizable for any pathogen for which an activity database can be created.

Eligibility for clinical trials in primary Sjögren's syndrome: lessons from the UK Primary Sjögren's Syndrome Registry.

OBJECTIVE: To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. METHODS: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. RESULTS: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. CONCLUSION: The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters.