Key drivers of hysterectomy among women of reproductive age in three states in India: comparative evidence from NFHS-4 and NFHS-5.

PURPOSE: According to the 4th and 5th rounds of National Family Health Survey (NFHS), there is high prevalence of hysterectomies in the three states of Andhra Pradesh Telangana and Bihar. The three said states have more than double the number of hysterectomies taking place than the national average. Our purpose is to analyse whether these rates are increasing, decreasing or have stabilized and their reasons thereof. Such an analyses will help the policy makers in recommending good clinical practices within their states. MATERIAL AND METHODS: We used data from NFHS-4 (2015-16) and NFHS-5 (2019-2021) rounds. We calculated the differences in predicted probabilities for various factors, performed a Fairlie Decomposition analyses to quantify the positive and negative contributors in the prevalence of hysterectomy across the three states over two time points, and assessed the association of various socio-demographic characteristics to hysterectomy through a multilevel logistic regression model. RESULTS AND CONCLUSION: The results show that out of a total of 80,976 eligible respondents from the states under study, 5826 respondents self-reported that they had a hysterectomy done. It was found that older age, living in rural areas, belonging to other backward classes and higher wealth quintile, and higher parity positively contributed to the increased prevalence of hysterectomies in the three states. Higher educational attainment and previous use of family planning methods acted as protective factors. Characteristics at the household level had the highest intra-class correlation value in the prevalence of hysterectomy among women, followed by the Primary Sampling Unit and District levels, indicating high clustering in the prevalence of hysterectomy at the household level in all three states. Heavy menstrual bleeding/pain was the leading cause of hysterectomies in all three states, followed by fibroids/cysts in Andhra Pradesh and Telangana and Uterine disorder/ prolapse in Bihar. Over 80% of hysterectomies took place in the private hospitals. RECOMMENDATIONS: The study recommends better, more efficient and accountable hysterectomy surveillance to ensure more sustainable woman's reproductive health services in India. Government should adopt and implement standard regulatory guidelines to prevent provider-driven avoidable hysterectomies. Moreover, we recommend informing primary care professionals about the long-term health effects of hysterectomy and promoting alternate therapies for treating uterine fibroids and heavy bleeding.

Chronic non-communicable disease burden among reproductive-age women in India: evidence from recent demographic and health survey.

BACKGROUND: Chronic disease burden among women leads to various detrimental consequences, impacting women's health throughout their life course and off-springs. The present study explores the chronic disease profile among reproductive-aged women and analyzes the effects of various covariates on multimorbidity among reproductive-aged women in India. Here, multimorbidity is defined as an individual suffering from two or more chronic conditions. METHODS: The present study employed the most recent National Family Health Survey round, 2019-2021. The study utilized information on 695,707 non-pregnant women aged 15-49 years. The study used descriptive, bivariate, and multivariable ordered logistic regression analysis to explore the burden of chronic non-communicable diseases and multimorbidity. RESULTS: The mean age of women with single chronic condition-related morbidity is 30 years, whereas it was 35 years for those with multimorbidity. Approximately 28% of urban women suffered from multimorbidity. Further, significant factors that affect multimorbidity include age, educational attainment, working status, marital status, parity, menopause, religion, region, wealth index, tobacco use, alcohol consumption, and dietary patterns. CONCLUSIONS: The present study hints that women in the reproductive age group are at very high risk of developing multimorbidity in India. Most of the programs and policies are focused on the elderly population in terms of awareness and facilitating them with better health services. However, right now, one should also prioritize the emerging chronic condition related to chronic conditions other than hypertension, diabetes, and cancer among the study population, which is escalating as soon as women reach 30 years of age.

Unraveling the genetic landscape of pulmonary arterial hypertension in Indian patients: A transcriptome study.

BACKGROUND: Pulmonary hypertension (PH) is the abnormal elevation of pressure in the pulmonary vascular system, with various underlying causes. A specific type of PH is pulmonary arterial hypertension (PAH), a severe condition characterized by high pulmonary arterial pressure resulting from structural changes in distal pulmonary vessels, altered arterial tone, and inflammation. This leads to right ventricular hypertrophy and heart failure. The molecular mechanisms behind PAH are not well understood. This manuscript aims to elucidate these mechanisms using the genetic tool, aiding in diagnosis and treatment selection. METHOD: In our present study, we have obtained blood samples from both patients with pulmonary arterial hypertension (PAH) and healthy individuals. We conducted a comparative transcriptome analysis to identify genes that are either upregulated or downregulated in PAH patients when compared to the control group. Subsequently, we carried out a validation study focusing on the log2-fold downregulated genes in PAH, employing Quantitative Real-Time PCR for confirmation. Additionally, we quantified the proteins encoded by the validated genes using the ELISA technique. RESULTS: The results of the transcriptome analysis revealed that 97 genes were significantly upregulated, and 6 genes were significantly downregulated. Among these, we chose to focus on and validate only four of the downregulated genes, as they were directly or indirectly associated with the hypertension pathway. We also conducted validation studies for the proteins encoded by these genes, and the results were consistent with those obtained in the transcriptome analysis. CONCLUSION: In conclusion, the findings of this study indicate that the four validated genes identified in the context of PAH can be further explored as potential targets for both diagnostic and therapeutic applications.

Quantitative tissue analysis reveals AK2, COL1A1, & PLG protein signatures: Targeted therapeutics for meningioma.

BACKGROUND: Meningioma is the most prevalent primary intracranial brain tumor and accounts for one-third of all CNS tumors. Meningioma is known to be the most common yet life-threatening brain tumor with a higher recurrence rate. Globally, there is an increase in the healthcare burden due to meningioma and hence in its research. The present clinical approach includes surgical resection, chemotherapy, and radiation therapies to which the malignancy does not seem to respond efficiently. Targeted therapies and molecular markers provide elite patient treatment and care for individuals suffering from meningiomas as compared to conventional measures. Although there is proteomic data on meningioma the knowledge of potential biomarkers differentiating the grades is scarce. To identify the best set of biomarkers, validation of reported markers in large and independent sample cohorts in the future is necessary. METHODS: A total of 12 samples, 3 each of control (which made pool 1) Meningioma grade I (which made 2 sets: pool 2 and pool 3), and Meningioma grade II (which made pool 4) were taken for LC-MS/MS. After this, the expression of three proteins was checked by immunocytochemistry, flow cytometry, and western blotting. RESULTS: Protein expression was analyzed using various techniques like mass spectrometry, immunocytochemistry, flow cytometry, and western blotting. Mass spectrometry is the most commonly used standard and reliable technique for identifying and quantifying protein expression. We got three highly upregulated proteins namely AK2, COL1A1, and PLG using this technique. The biomarker potential of these proteins was further checked by ICC, western blotting, and flow cytometry. Three important proteins were found to be upregulated namely AK2 (Adenylate Kinase 2), COL1A1 (Collagen 1A1), and PLG (Plasminogen). The order of increased protein expression was control < MG grade I < MG grade II according to mass spectrometry and western blotting. In immunocytochemistry, we found that COL1A1 expression increases significantly with grades in comparison to control. Similarly, AK2 and PLG also showed little increase but not as much as COL1A1. In flow cytometry, PLG showed higher upregulation in grades than control. While AK2 and COL1A1 showed little increase in expression in grades than control. All techniques, especially mass spectrometry and western blotting presented higher expression of these proteins in grades as compared to control. CONCLUSIONS: In the quest to find a suitable therapeutic marker, this study incorporates quantitative labeling and detection followed by flow cytometry, Immunocytochemistry, and western blotting for early diagnosis and treatment of meningioma. The article further explores the efficacy of some proteins namely AK2, COL1A1 & PLG to be the targeted molecules.

Factors Contributing to the Change in Overweight/Obesity Prevalence Among Indian Adults: A multivariate decomposition analysis of data from the National Family Health Surveys.

INTRODUCTION: Concerns over the escalating burden of non-communicable diseases call for the redressal of behavioral risk factors like increased body mass index. Most studies have failed to quantify the contribution of socio-demographic characteristics in a linear trend. The present study aims to estimate the current prevalence of overweight and obesity in Indian adults and the contribution of different socio-demographic factors to the increasing prevalence. METHODS: We carried out a secondary data analysis of two National Family Health Survey (NFHS) rounds. The final sample includes 558,122 women and 84,477 men from round 4, and 574,099 women and 74,761 men were included from round 5, using a multi-stage stratified random sampling approach. Overweight/obesity was our primary dependent variable. Weighted bivariate analysis was used to ascertain the prevalence, and the adjusted odds ratios were computed to ascertain the potential predictors. The contribution of different factors towards rising burden over two time points was estimated using multivariate decomposition analysis for non-linear response models. RESULTS: Overall weighted prevalence of overweight and obesity in males and females per NFHS-5 was 44.02% and 41.16%, respectively, compared to 37.71% and 36.14% in NFHS-4. Decomposition analyses depict that the proportion of obesity increased by 6.37% and 5.10% points among men and women, respectively, over the two rounds. Compositional differences of participants (endowment) attributed to 16.54 and 49.90% differences, and the difference in coefficient or effect accounted for 83.46 and 50.10%, respectively, of the increase in the prevalence. The most significant factors contributing to increased prevalence were age, improving socio-economic status, smoking, unclean cooking fuel, and diabetes. CONCLUSIONS: The incremental rise in such a short period, mainly attributed to the effect of socio-demographic variables, is concerning. Policy interventions should prioritize health advocacy programs and aggressively target behavioral modifications while preparing the health systems to manage the people living with obesity.

Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population.

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.

Cytochrome C as a potential clinical marker for diagnosis and treatment of glioma.

Gliomas are the most prevalent kind of malignant and severe brain cancer. Apoptosis regulating mechanisms are disturbed in malignant gliomas, as they are in added forms of malignancy. Understanding apoptosis and other associated processes are thought to be critical for understanding the origins of malignant tumors and designing anti-cancerous drugs for the treatment. The purpose of this study was to evaluate the variation in the expression level of several apoptotic proteins that are responsible for apoptosis in low to high-grade glioma. This suggests a significant change in the expression of five apoptotic proteins: Clusterin, HSP27, Catalase, Cytochrome C, and SMAC. Cytochrome C, one of the five substantially altered proteins, is a crucial component of the apoptotic cascade. The complex enzyme Cytochrome C is involved in metabolic pathways such as respiration and cell death. The results demonstrated that Cytochrome C expression levels are lower in glioma tissues than in normal tissues. What's more intriguing is that the expression level decreases with an increase in glioma grades. As a result, the discovery shows that Cytochrome C may be a target for glioma prognostic biomarkers.

Survival Analysis of Patients With COVID-19 in India by Demographic Factors: Quantitative Study.

BACKGROUND: Studies of the transmission dynamics of COVID-19 have depicted the rate, patterns, and predictions of cases of this pandemic disease. To combat transmission of the disease in India, the government declared a lockdown on March 25, 2020. Even after this strict lockdown was enacted nationwide, the number of COVID-19 cases increased and surpassed 450,000. A positive point to note is that the number of recovered cases began to slowly exceed that of active cases. The survival of patients, taking death as the event that varies by age group and sex, is noteworthy. OBJECTIVE: The aim of this study was to conduct a survival analysis to establish the variability in survivorship of patients with COVID-19 in India by age group and sex at different levels, that is, the national, state, and district levels. METHODS: The study period was taken from the date of the first reported case of COVID-19 in India, which was January 30, 2020, up to June 30, 2020. Due to the amount of underreported data and removal of missing columns, a total sample of 26,815 patients was considered. Kaplan-Meier survival estimation, the Cox proportional hazard model, and the multilevel survival model were used to perform the survival analysis. RESULTS: The Kaplan-Meier survival function showed that the probability of survival of patients with COVID-19 declined during the study period of 5 months, which was supplemented by the log rank test (P<.001) and Wilcoxon test (P<.001) to compare the survival functions. Significant variability was observed in the age groups, as evident from all the survival estimates; with increasing age, the risk of dying of COVID-19 increased. The Cox proportional hazard model reiterated that male patients with COVID-19 had a 1.14 times higher risk of dying than female patients (hazard ratio 1.14; SE 0.11; 95% CI 0.93-1.38). Western and Central India showed decreasing survival rates in the framed time period, while Eastern, North Eastern, and Southern India showed slightly better results in terms of survival. CONCLUSIONS: This study depicts a grave scenario of decreasing survival rates in various regions of India and shows variability in these rates by age and sex. In essence, we can safely conclude that the critical appraisal of the survival rate and thorough analysis of patient data in this study equipped us to identify risk groups and perform comparative studies of various segments in India. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1101/2020.08.01.20162115.

Role of Extracellular Vesicles in Glioma Progression: Deciphering Cellular Biological Processes to Clinical Applications.

Glioma predominantly targets glial cells in the brain and spinal cord. There are grade I, II, III, and IV gliomas with anaplastic astrocytoma and glioblastoma multiforme as the most severe forms of the disease. Current diagnostic methods are limited in their data acquisition and interpretation, markedly affecting treatment modalities, and patient outcomes. Circulating extracellular vesicles (EVs) or "magic bullets" contain bioactive signature molecules such as DNA, RNA, proteins, lipids, and metabolites. These secretory "smart probes" participate in myriad cellular activities, including glioma progression. EVs are released by all cell populations and may serve as novel diagnostic biomarkers and efficient nano-vehicles in the targeted delivery of encapsulated therapeutics. The present review describes the potential of EV-based biomarkers for glioma management.

Plasma-Derived Extracellular Vesicles Reveal Galectin-3 Binding Protein as Potential Biomarker for Early Detection of Glioma.

Gliomas are the most common type of the malignant brain tumor, which arise from glial cells. They make up about 40% of all primary brain tumors and around 70% of all primary malignant brain tumors. They can occur anywhere in the central nervous system (CNS) and have a poor prognosis. The average survival of glioma patients is approximately 6-15 months with poor aspects of life. In this edge, identification of proteins secreted by cancer cells is of special interest because it may provide a better understanding of tumor progression and provide early diagnosis of the diseases. Extracellular vesicles (EVs) were isolated from pooled plasma of healthy controls (n=03) and patients with different grades of glioma (Grade I or II or III, n=03 each). Nanoparticle tracking analysis, western blot, and flow cytometry were performed to determine the size, morphology, the concentration of glioma-derived vesicles and EV marker, CD63. Further, iTRAQ-based LC-MS/MS analysis of EV protein was performed to determine the differential protein abundance in extracellular vesicles across different glioma grades. We further verified galectin-3 binding protein (LGALS3BP) by ELISA in individual blood plasma and plasma-derived vesicles from control and glioma patients (n=40 each). Analysis by Max Quant identified 123 proteins from the pooled patient exosomes, out of which 34, 21, and 14 proteins were found to be differentially abundant by more than 1.3-fold in the different grades of glioma grade I, pilocytic astrocytoma; grade II, diffuse astrocytoma; grade III, anaplastic astrocytoma, respectively, in comparison with the control samples. A total of seven proteins-namely, CRP, SAA2, SERPINA3, SAA1, C4A, LV211, and KV112-showed differential abundance in all the three grades. LGALS3BP was seen to be upregulated across the different grades, and ELISA analysis from individual blood plasma and plasma-derived extracellular vesicles confirmed the increased expression of LGALS3BP in glioma patients (p<0.001). The present study provides LGALS3BP as a potential biomarker for early detection of glioma and improve survival outcome of the patient. The present study further provides the information of progression and monitoring the tumor grades (grade 1, grade II, grade III).

Exploring the role of epidermal growth factor receptor variant III in meningeal tumors.

Meningioma is the second most common type of intracranial brain tumor. Immunohistochemical techniques have shown prodigious results in the role of epidermal growth factor receptor variant III (EGFR vIII) in glioma and other cancers. However, the role of EGFR vIII in meningioma is still in question. This study attempt the confer searches for the position attained by EGFR vIII in progression and expression of meningioma. Immunohistochemistry technique showed that EGFR vIII is highly expressed in benign tumors as compared to the atypical meningioma with a highly significant p-value (p<0.05). Further analysis by flow cytometry results supported these findings thus presented high intensity of EGFR vIII in low grades of meningioma. The study revealed that the significant Ki 67 values, to predictor marker for survival and prognosis of the patients. Higher expression of EGFR vIII in low grades meningiomas as compared to high-grade tumors indicate towards its oncogenic properties. To our knowledge, limited studies reported in literature expressing the EGFR vIII in meningioma tumors. Hence, Opinions regarding the role that EGFR vIII in tumorigenesis and tumor progression are clearly conflicting and, therefore, it is crucial not only to find out its mechanism of action, but also to definitely identify its role in meningioma.

To identify predictors of relapse in cases of alcohol dependence syndrome in relation to life events.

BACKGROUND AND OBJECTIVES: Relapse is a complex and dynamic phenomenon that appears to be determined by biological, psychological, and social factors and an interaction among these. This study examined the association between demographic variables, clinical parameters, and psychosocial factors that predict the vulnerability to relapse in cases of alcohol dependence syndrome. MATERIALS AND METHODS: Structured assessments of clinical/demographic parameters, relapse precipitants, life events, and dysfunction were carried out among patients with alcohol dependence syndrome (n = 100) who had relapsed and compared with those (n = 100) who had managed to remain abstinent. RESULTS: Patients who had relapsed were found to have significantly more positive family history of substance use, past history of alcohol-related comorbidity, experienced a higher number of undesirable life events, and higher negative mood states and social anxiety and dysfunction in social, vocational, personal, family, and cognitive spheres compared to patients who had remained abstinent. CONCLUSIONS: Relapse in alcohol dependents is an interaction of many factors, and multiple layers of assessment may be required to predict relapse. This study provided further evidence in support of the importance of certain clinical/psychosocial factors in relapse in substance dependence. It provides the basis for investigating the correlates of relapse in a wide range of behavioral and substance use problems.

Effect of bromelain enzyme for dentin deproteinization on bond strength of adhesive system.

AIMS: To assess the deproteinizing effect of bromelain enzyme and compare it with 5% sodium hypochlorite (NaOCl) on shear bond strength before application of the adhesive system. MATERIALS AND METHODS: A total of 30 extracted human premolars were divided into three groups, each one consisted of 10 teeth. The occlusal surface was wet ground to expose superficial dentin. In Group 1, teeth were etched; in Group 2, teeth were etched and deproteinized with bromelain enzyme; in Group 3, teeth were etched and deproteinized with 5% NaOCl. Upon completion of the adhesive procedures, resin composite was inserted into the plastic tube and light-polymerized. All specimens were stored at 37°C in water for 24 h, and the specimens were transferred to the universal testing machine, and then subjected to shear bond strength analysis at a crosshead speed of 1.0 mm/min. STATISTICAL ANALYSIS USED: Data were statistically analyzed using one-way analysis of variance and unpaired t-test at a significance level of 0.05. The statistical analysis was performed using SPSS version 12.0.1 for Windows (SPSS Inc., Chicago, IL, USA). RESULTS: The bond strength results were significantly influenced by the application of bromelain enzyme. Statistically significant differences were not demonstrated in control group and NaOCl-treated group. The highest bond strength was seen in bromelain enzyme-treated group. CONCLUSIONS: Within the limitations of the present study, it was concluded that removal of unsupported collagen fiber with bromelain enzyme after acid etching results in improved bond strength.