"Association of Leptin with Polycystic Ovary Syndrome: a Systematic Review and Meta-Analysis".

BACKGROUND: Serum leptin has been considered as an important measurable diagnostic and prognostic biomarker for polycystic ovarian syndrome (PCOS), although its evidence for use in clinical practice is limited. We aim to synthesize the available evidence on the clinical use of serum leptin values in PCOS by doing a systematic review and meta-analysis of studies. OBJECTIVE: To conduct a meta-analysis to determine the pooled effect size of the association of leptin levels in patients with PCOS. METHODS: We searched electronic databases, i.e., PubMed, Google Scholar, Web of Science, ClinicalTrials.gov, and Medline from inception to September 2020, keeping filters for human studies and published in the English language. We used the random-effects model if heterogeneity between the studies was > 50%; otherwise, a fixed-effect model was applied to determine the standardized mean difference with 95% CI for comparison of leptin level between cases and controls. All the statistical analyses were completed using software STATA version 13. RESULTS: The meta-analysis included a total of 35 studies involving 2015 cases and 1767 controls that suggested statistically significantly higher leptin levels in the women with PCOS as compared to controls (SMD, 1.76, 95% CI 1.28 to 2.23, P < 0.001). In the stratified analysis when only high methodological quality studies were included, we did not observe a statistically significant difference in the leptin level between PCOS and controls (SMD 0.68, 95% CI -0.09 to 1.46). Analysis restricted to low methodological quality studies observed statistically significant high leptin levels in PCOS women as compared to controls (SMD 2.24, 95% CI 1.65 to 2.83). CONCLUSION: The available evidence suggests that elevated leptin levels may be associated with risk of PCOS as compared to controls; however, failure to observe the similar association in high methodological quality studies demands further well-designed adequately powered studies to validate the findings.

Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Vitamin C has been used as an anti-oxidant in various diseases including viral illnesses like coronavirus disease (COVID-19). METHODS: Meta-analysis of randomized controlled trials (RCT) investigating the role of vitamin C supplementation in COVID-19 was carried out. RESULTS: Total 6 RCTs including n = 572 patients were included. Vitamin C treatment didn't reduce mortality (RR 0.73, 95% CI 0.42 to 1.27; I2 = 0%; P = 0.27), ICU length of stay [SMD 0.29, 95% CI -0.05 to 0.63; I2 = 0%; P = 0.09), hospital length of stay (SMD -0.23, 95% CI -1.04 to 0.58; I2 = 92%; P = 0.57) and need for invasive mechanical ventilation (Risk Ratio 0.93, 95% CI 0.61 to 1.44; I2 = 0%; P = 0.76). Further sub-group analysis based on severity of illness (severe vs. non-severe), route of administration (IV vs. oral) and dose (high vs. low) failed to show any observable benefits. CONCLUSION: No significant benefit noted with vitamin C administration in COVID-19. Well-designed RCTs with standardized control group needed on this aspect.

Impact of COVID-19 outbreak on lifestyle behaviour: A review of studies published in India.

BACKGROUND AND AIMS: The entire globe is undergoing an unprecedented challenge of COVID-19 which has affected the lifestyle behaviour of individuals. The present review is an attempt to summarize the effect of pandemic COVID-19 on lifestyle behaviour among the Indian population. METHODS: A review was carried out to summarize the effect of pandemic COVID-19 on lifestyle behaviour focusing on changes in dietary or eating behaviour, stress, sleep pattern, and level of physical activity among the Indian population. Literature searches were conducted in PubMed and Google Scholar from inception till October 2020 to identify all relevant studies. RESULTS: A total of 11 studies (n = 5957, age group 18-70 years, comprising both genders) consisting of 1 hospital and 10 community based, were included in the present review. A change in lifestyle behaviour was observed due to COVID-19. Psychosocial or any kind of mental stress among the participants was found to be prevalent. Weight gain and decline in physical activity were also observed. Not only sleep quantity but sleep quality was also found to be affected due to COVID-19. CONCLUSION: The present review indicates the need for lifestyle behaviour programmes via using the platform of E-media and also for the dissemination of health education.

Incremental Accuracy of Blood Biomarkers for Predicting Clinical Outcomes After Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with high mortality, morbidity, and recurrence. Studies have reported the accuracy of several blood biomarkers in predicting clinical outcomes; however, their independent contribution in prediction remains to be established. AIM: To investigate the incremental accuracy in predicting clinical outcomes in patients with ICH in a north Indian population using blood-based biomarkers. METHODS: In this study, a total of 250 ICH cases were recruited within 72 hours of onset. Baseline clinical and CT scan measurement were recorded. Homocysteine (HCY), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP9), E-selectin (SELE), and P-selectin (SELP) levels were measured through ELISA. Telephonic follow-up was done by using mRS scale at three months. RESULTS: The mean age of cohort was 54.9 (SD±12.8) years with 64.8% patients being male. A total of 109 (43.6%) deaths were observed over three months follow-up. Area under the receiver operating characteristics curve-(AUROC) for 90-day mortality were 0.55 (HCY), 0.62 (CRP), 0.57 (MMP9), 0.60 (SELE) and 0.53 (SELP) and for poor outcome at 90-day (mRS: 3-6) were 0.60 (HCY), 0.62 (CRP), 0.54 (MMP9), 0.67 (SELE) and 0.54 (SELP). In multivariable model including age, ICH volume, IVH and GCS at admission, serum SELE (p=0.004) significant for poor outcome with improved AUROC (0.86) and HCY (p=0.04), CRP (p=0.003) & MMP9 (p=0.02) for mortality with least Akaike's Information Criterion-(AIC) (1060.5). CONCLUSIONS: Our findings suggest that the serum SELE is a significant predictor of poor outcome and HCY, CRP & MMP9 for Mortality in patients with ICH in the north Indian population.

Association between matrix metalloproteinase family gene polymorphisms and risk of ischemic stroke: A systematic review and meta-analysis of 29 studies.

BACKGROUND: Ischemic stroke (IS) is a complex and devastating vascular disease that has become one of the leading causes of disability and mortality worldwide. Several studies have shown the association between matrix metalloproteinase (MMP) family gene polymorphisms and IS. However, the results have been indecisive. OBJECTIVE: To investigate the association between Matrix Metalloproteinase gene polymorphisms and risk of IS. METHODS: A literature search for eligible candidate gene studies published before, 28 June 2017, was conducted in the PubMed, EMBASE, Cochrane and Google Scholar databases. The following combinations of main keywords were used: ('Matrix Metalloproteinase' or 'MMP' or 'Stromelysin-1' or 'Gelatinase b') AND ('ischemic stroke' or 'IS') AND ('single nucleotide polymorphism' or 'gene polymorphism' or 'SNP'). Fixed or random effects models were used to estimate the Pooled Odds ratio (OR) and 95% confidence interval (CI). Statistical analysis was carried out by using STATA version 13.0 software. RESULTS: Total 29 studies were included in our meta-analysis. A significant association was observed for MMP-9 (-1562C/T) (OR 1.27; 95% CI 1.06 to 1.53; p value = 0.01) and MMP-12 (-1082 A/G) (OR 2.55; 95% CI 1.75 to 3.71; p value<0.001) gene polymorphisms and risk of IS. No significant association was found for any of the MMP-1(-1607 1G/2G), MMP-2 (-1306C/T) & (-735C/T) and MMP-3 (-1612 5A/6A) gene polymorphisms with the risk of IS. CONCLUSION: Our meta-analysis suggests that MMP-9 (-1562C/T) and MMP-12 (-1082 A/G) gene polymorphisms could be a risk factor for IS while MMP-1 (-1607 1G/2G), MMP-2 (-1306C/T) & (-735C/T) and MMP-3 (-1612 5A/6A) have no association with the risk of causing IS. However, large prospective studies with sufficient power are required to validate our findings.

Relationship of phosphodiesterase 4D (PDE4D) gene polymorphisms with risk of ischemic stroke: a hospital based case-control study.

BACKGROUND: Stroke remains a leading cause of death and disability worldwide. Ischemic stroke (IS) accounts for around 80-85% of total stroke and is a complex polygenic multi-factorial disorder which is affected by a complex combination of vascular, environmental, and genetic factors. OBJECTIVE: The study was conducted with an aim to examine the relationship of single nucleotide polymorphisms (SNPs) of PDE4D (T83C, C87T, and C45T) gene with increasing risk of IS in patients in North Indian population. METHODS: In this hospital-based case-control study, 250 IS subjects and 250 age-and sex-matched control subjects were enrolled from the Neurosciences Centre, A.I.I.M.S., New Delhi, India. Deoxyribonucleic acids (DNAs) were extracted using the conventional Phenol-Chloroform isolation method. Different genotypes were determined by Polymerase chain reaction- Restriction fragment length polymorphism method. Odds ratio (OR) and 95% Confidence Interval (CI) of relationship of polymorphisms with risk of IS were calculated by conditional multivariable regression analysis. RESULTS: High blood pressure, low socioeconomic status, dyslipidemia, diabetes, and family history of stroke were observed to be statistically significant risk factors for IS. Multivariable adjusted analysis demonstrated a statistically significant relationship between SNP 83 of PDE4D gene polymorphism and increasing odds of IS under the dominant model of inheritance (OR, 1.59; 95% CI, 1.02 to 2.50; p value = 0.04) after adjustment of potential confounding variables. Stratified analysis on the basis of TOAST classification demonstrated a statistically significant association for increasing 2.73 times odds for developing large vessel disease stroke as compared to controls (OR, 2.73; 95% CI, 1.16 to 0.02; p value = 0.02). We did not find any significant association of SNPs (C87T and C45T) of the PDE4D gene with the risk of IS. CONCLUSION: SNP 83 of PDE4D gene may increase the risk for developing IS whereas SNP 87 and SNP45 of PDE4D may not be associated with the risk of IS in the North Indian population. Prospective cohort studies are required to corroborate these findings.

Association between endothelial nitric oxide synthase gene polymorphisms and risk of ischemic stroke: A meta-analysis.

Previously published studies that have examined whether the three polymorphisms, G894T, T786C, and 4b/a in the endothelial nitric oxide synthase (eNOS) gene, are associated with ischemic stroke (IS) have reported conflicting results. Thus, we performed a meta-analysis to examine the potential association between these three single nucleotide polymorphisms (SNPs) of the eNOS gene and IS risk. A literature search was carried out for eligible candidate gene studies published before August 05, 2015 in the PubMed, Embase, and Google Scholar databases. The following combinations of main keywords were used in our study: ('endothelial nitric oxide synthase') or ('eNOS') and ('G894T, 4b/a, and T786C') and ('polymorphism') or ('polymorphisms') and ('Ischemic Stroke' or 'IS') and ('Cerebral Infarction' or 'CI') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using fixed or random effects model. Meta-regression analysis was used to investigate the potential sources of heterogeneity. Begg's funnel plots were used to explore the publication bias, and heterogeneity was assessed by I2 test. Twenty seven case-control studies involving 6733 cases and 7305 controls were analyzed in our meta-analysis. Significant association was observed for G894T (OR = 1.17; 95% CI: 1.08 to 1.28; P< 0.001) and 4b/a (OR = 1.25; 95% CI: 1.13 to 1.39; P < 0.001) whereas a non-significant association was observed for T786C (OR = 1.11; 95% CI: 0.98 to 1.26; P =0.109) eNOS gene polymorphisms and IS. Our meta-analysis establishes that the G894T and 4b/a polymorphisms of eNOS gene are significantly associated with the risk of IS. However, a non-significant association was found between T786C polymorphism of the eNOS gene and IS risk. Further prospective large epidemiological studies need to be done to confirm these findings.

Closing the loop overnight at home setting: psychosocial impact for adolescents with type 1 diabetes and their parents.

OBJECTIVE: To explore the experiences of adolescents with type 1 diabetes mellitus (T1DM) and their parents taking part in an overnight closed loop study at home, using qualitative and quantitative research methods. RESEARCH DESIGN AND METHODS: Adolescents aged 12-18 years on insulin pump therapy were recruited to a pilot closed loop study in the home setting. Following training on the use of a study insulin pump and continuous glucose monitoring (CGM), participants were randomized to receive either real-time CGM combined with overnight closed loop or real-time CGM alone followed by the alternative treatment for an additional 21 days with a 2-3-week washout period in between study arms. Semistructured interviews were performed to explore participants' perceptions of the impact of the closed loop technology. At study entry and again at the end of each 21-day crossover arm of the trial, participants completed the Diabetes Technology Questionnaire (DTQ) and Hypoglycemia Fear Survey (HFS; also completed by parents). RESULTS: 15 adolescents and 13 parents were interviewed. Key positive themes included reassurance/peace of mind, confidence, 'time off' from diabetes demands, safety, and improved diabetes control. Key negative themes included difficulties with calibration, alarms, and size of the devices. DTQ results reflected these findings. HFS scores were mixed. CONCLUSIONS: Closed loop insulin delivery represents cutting-edge technology in the treatment of T1DM. Results indicate that the psychological and physical benefits of the closed loop system outweighed the practical challenges reported. Further research from longitudinal studies is required to determine the long-term psychosocial benefit of the closed loop technology.

Prevalence of human papillomavirus infection among young women in North India.

BACKGROUND: The number of women infected with human papillomavirus (HPV) and the distribution of the HPV genotypes vary across populations and with age. OBJECTIVE: To determine the prevalence and genotype distribution of HPV in young married women aged 16-24 years. METHODS: 1300 women residing in an urban slum in Delhi donated samples of exfoliated cervical cells that were collected by the Digene((R)) kit and tested for the presence of HPV DNA by two techniques in parallel, i.e., PCR using PGMY consensus primers for all HPV types and the Digene HPV test (Hybrid Capture 2 (HC2) Probe B for high-risk (hr) types. Genotyping was done on all HPV positive samples using the Roche reverse line blot assay. RESULTS: HPV infection was detected in 91/1300 (7%) samples by PCR and 110/1300 (8.4%) samples by HC2. Genotyping identified 20 high-risk and 11 low-risk types. HPV16 was the commonest high-risk type (3%) followed by HPV52 (1.2%) and HPV51 (0.8%). Among low-risk types, HPV62 was the commonest (0.8%), followed by HPV84 and HPV89 (0.5% each). Multiple infections were found in 3% of the HPV positive samples. CONCLUSION: A wide spectrum of HPV genotypes is seen in this young population. Knowledge about HPV types prevalent in communities in different regions of India would be useful in devising the optimum strategy for cervical cancer prevention.

Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?

BACKGROUND: To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology. METHODS: This was a cross-sectional study of 546 sexually active women aged > or =30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (kappa) and Chi-square test. RESULTS: Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (kappa=76.31%, 95% confidence interval [CI]: 64.97-82.29%, p=0.04)-complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (kappa=63.7%, 95% CI: 55.2-72.2%) and 95.3% for physician-collected samples (kappa=80.4%, 95% CI: 71.8-89.0%). CONCLUSIONS: Self-HPV sampling compares favourably with physician-sampling and cytology. A rapid, affordable, HPV self-test kit can be used as the primary method of cervical cancer screening in low-resource situations.

Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction.

Impaired ribosome biogenesis is attributed to nucleolar disruption and diffusion of a subset of 60S ribosomal proteins, particularly ribosomal protein (rp)L11, into the nucleoplasm, where they inhibit MDM2, leading to p53 induction and cell-cycle arrest. Previously, we demonstrated that deletion of the 40S rpS6 gene in mouse liver prevents hepatocytes from re-entering the cell cycle after partial hepatectomy. Here, we show that this response leads to an increase in p53, which is recapitulated in culture by rpS6-siRNA treatment and rescued by the simultaneous depletion of p53. However, disruption of biogenesis of 40S ribosomes had no effect on nucleolar integrity, although p53 induction was mediated by rpL11, leading to the finding that the cell selectively upregulates the translation of mRNAs with a polypyrimidine tract at their 5'-transcriptional start site (5'-TOP mRNAs), including that encoding rpL11, on impairment of 40S ribosome biogenesis. Increased 5'-TOP mRNA translation takes place despite continued 60S ribosome biogenesis and a decrease in global translation. Thus, in proliferative human disorders involving hypomorphic mutations in 40S ribosomal proteins, specific targeting of rpL11 upregulation would spare other stress pathways that mediate the potential benefits of p53 induction.

Evaluation of cervical screening in rural North India.

OBJECTIVE: To assess the accuracy of cervical screening with visual inspection and cytology testing, and the cure rate of cervical intraepithelial neoplasia (CIN) after treatment, in a rural population in North India. METHODS: A cross-sectional study evaluated the detection rates of CIN 2 and CIN 3 lesions by cytology testing and by visual inspection of the cervix following the application of 5% acetic acid (VIA) or Lugol's iodine (VILI). It also evaluated the cure rates following treatment of CIN. RESULTS: Of 5050 women approached in 17 villages, 3000 (59.4%) participated (range, 41%-91%). Of these, 14.2% were positive by VIA, 15.6% by VILI, and 5.4% by cytology testing at ASCUS threshold, and 37 women were diagnosed as having CIN 1 and 20 as having CIN 2 or CIN 3. Detection rates of CIN 2 or 3 using VIA, VILI, and cytologic findings of ASCUS and LSIL were 3.7, 3.3, 4.5, and 4.2 per 1000 women, respectively, and 91.4% of the treated women were cured. CONCLUSION: Both VIA and VILI were found to be accurate screening tests and the cure rates for CIN were satisfactory.

Human papillomavirus-type distribution in women with and without cervical neoplasia in north India.

Our objective was to determine the human papillomavirus (HPV)-type prevalence in cervical samples in women with and without cervical neoplasia in an opportunistic hospital-based cancer-screening program. A cross-sectional study of 524 women presenting from January 2003 through June 2005 with symptoms of persistent vaginal discharge, intermenstrual bleeding, and postcoital bleeding or detected to have an unhealthy cervix underwent HPV genotyping by consensus polymerase chain reaction and reverse line-blot hybridization assay, conventional Pap smear, and colposcopy, with directed biopsy from all lesions detected. The prevalence rates of HPV infection among women with normal, low-grade cervical neoplasia (CIN 1) and high-grade CIN (>CIN2) were found to be 7.6%, 42.3%, and 87.5%, respectively. Seventeen high-risk and 6 low-risk HPV types were identified by the reverse line-blot assay. Multiple infections were seen in 20% of women. In normal women, the 6 commonest types were HPV-16, HPV-89, HPV-39, HPV-52, HPV-62, and HPV-18, whereas in high-grade disease, these were all high-risk types HPV-16, HPV-18, HPV-33, HPV-39, HPV-35, and HPV-56. HPV-16 was the commonest type in all groups, seen in 49.4% cases overall and in 74.3% of high-grade squamous intraepithelial lesion. It was followed by HPV-18 (7.4%) and HPV-33 and HPV-39 (4.9% each). HPV-89 was the commonest low-risk type (9.9%). HPV-16/18 were associated with 34.3% of normal, 45.4% of low-grade and 65.7% of high-grade lesions. A wide spectrum of HPV types is seen in north Indian women, with the majority being HPV-16 in all grades of histology. A vaccine against HPV-16 and HPV-18 could prevent two thirds of cases of high-grade cervical neoplasia.

Human papillomavirus type distribution in cervical cancer in Delhi, India.

This hospital-based study in New Delhi, North India was performed to evaluate the prevalence of human papillomavirus (HPV) in cases of invasive cervical carcinoma (ICC). A total of 10 cases presenting with an obvious cervical growth were included in this study. 108 cases that was shown to be ICC on histology (101 squamous cell carcinomas, 4 adenocarcinomas, and one neuroendocrine carcinoma) were included in the analysis. DNA was extracted from tumor tissue and HPV genotype was determined by a consensus PCR assay using a reverse line blot hybridization assay. Of 106 evaluable cases, 104 (98.1%) were positive for HPV infection. Twelve different high-risk HPV types were found. There were 125 infections, 119 of which were high risk. Six cases had associated low risk infections. HPV 16 was the commonest type, seen in 73.6% cases followed by HPV 18 (14.2%) and 45 (11.3%). A vaccine with 100% efficacy in prevention of HPV 16 and 18 infections would theoretically reduce the total cancer burden in New Delhi by more than 75% (assuming 100% coverage). Increasing the genotype spectrum (e.g. valency) if the existing vaccines would be expected to have only a modest impact on the potential for cervical protection.