HPLC Method Development and Validation for Estimation of Chlorthalidone in Tablet Dosage Form

The present work relates to development and validation of simple, precise and rapid high-performance liquid chromatographic (HPLC) method for the analysis of Chlorthalidone in tablet dosage form. Method was developed for qualitative and quantitative estimation of Chlorthalidone in tablet dosage form. The chromatographic separation was achieved by using mobile phase 20 mM potassium dihydrogen orthophosphate buffer pH 4.0: methanol (30:70 %v/v) on HiQ Sil C8 (4.6 mm*250 mm* 5μm) column. The mobile phase was pumped at a flow rate of 1.0 ml/min and the eluent was monitored at 230 nm. Retention time was 3.334±0.042 min. Linearity was observed in the concentration range of 5-30 μg/ml with a correlation coefficient (R2) of 0.9915. All the parameters were validated as per ICH guidelines and found to be suitable for routine analysis of drug in pharmaceutical dosage form. Keywords: Chlorthalidone, Quantitative and Qualitative estimation, HPLC.&nbsp

Chemical composition and isotopic signatures of ice and snow over a Himalayan Glacier (Satopanth) in India

This study reports the chemical composition and isotopic signatures of snow and ice over a Himalayan Glacier in India. An observational campaign was carried out from September 22, 2016, to October 2, 2016, over Satopanth in central Himalaya. The pH value of ice and snow, respectively, was 5.6 ± 0.4 and 5.9 ± 0.35 over the glacier, indicating moderate acidity of the glacier components. Calcium (Ca2+) was the dominant component in snow (35.2%), while sulfate (SO42−) was dominant in ice samples (52.7%). The neutralization factor was estimated to find the extent of neutralization of acidic fractions by basic components. It is found that Ca2+ was the prominent neutralizing factor both in snow and ice over the region. Oxygen and hydrogen isotopic analyses of snow, surface layer ice and debris-covered ice suggest that the moisture source is common for all three components. δD and d-excess values of snow at Satopanth are different than that of those for Chorabari, Dokriani and Tiprabank Glacier, indicating the plausibility of different sources of moisture for these glaciers. Limited observations suggest that the interaction of ice with the debris has no impact on the isotopic signatures of the ice over the region; such non-alteration of isotopic signatures makes the region important for ice core-based paleoclimatic studies

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Mann Ki Baat - Present and Future

The main aim of this study is to learn about how people feel about this radio show and similarly what people actually feel should be implemented if possible for getting more benefits from it in respect ofvarious subjects which can help the masses in more effective way. References from few papers were studied too as they mainly focused on what is the effect of this show economically or socially and what people should expect from this show in future but this research paper helps in understanding, what people really need than to expect and likewise what people feel would be beneficial for them rather than making assumptions about requirements of the masses. This research paper have alsofocused on theories already made about the show to get broad idea regarding the analysis of current trend set about the show to produce a product which helps everyone who comes across the paper with our input and study. Similarly, the study helps us in understanding real time expectations and  deliverables that happen in India in current times with the hope of getting a better future for the show and satisfaction in the terms of peoples’ requirements

VITAMIN D STATUS AND ITS EFFECT ON FUNCTIONAL OUTCOME IN PATIENTS WITH HIP FRACTURE: AN OBSERVATIONAL STUDY

Aims and Objectives: The study aimed to study the Vitamin D status of adult patients presenting with hip fractures and analyze potential impact of Vitamin D status on outcome of these patients. Methods: This was an observational study of Vitamin D status of patients presenting with hip fractures. It was conducted in the department of orthopedics of a tertiary care medical college. One hundred and twenty adult patients presenting with hip fractures were included in this study on the foundation of a predefined inclusion and exclusion criteria. Demographic details of all the patients such as age, gender, and socioeconomic status were noted. Vitamin D status of patients was determined and correlated with functional outcome at the time of final follow-up visit at 6 months. Results: Among the 120 studied with hip fractures, 64 cases (53.33%) involved females, while 56 cases (46.67%) involved males having a M: F ratio of 1:1.14. The mean age of male and female patients was found to be 45.85±10.12 and 46.74±9.86 years. Overall, 65 (54.17%) patients were Vitamin D sufficient and remaining 55 (45.83%) were either inefficient (26.67%) or deficient (19.17%). Seventy-three (60.83%) patients had excellent to good outcome whereas 31 (25.83%) patients had fair outcome. Out of remaining 16 patients, 11 (9.17%) patients had poor outcome and 5 (4.17%) patients had very poor outcome. The patients with sufficient Vitamin D status were found to have a better outcome as compared to those patients with inefficient or deficient Vitamin D status and the difference was found to be statistically significant (p=0.01). Conclusion: It is significant to treat Vitamin D deficiency in patients presenting with hip fractures as Vitamin D deficiency is associated with suboptimal functional outcome in cases with hip fractures

Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from India

Background: This post hoc analysis evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) from India. Methods: Changes from baseline in HbA1c, fasting plasma glucose (FPG), body weight, and blood pressure (BP) with canagliflozin 100 and 300 mg were evaluated in a subgroup of patients from India (n = 124) from 4 randomized, double-blind, placebo- and active-controlled, Phase 3 studies (N = 2313; Population 1). Safety was assessed based on adverse event (AE) reports in these patients and in a broader subgroup of patients from India (n = 1038) from 8 randomized, double-blind, placebo- and active-controlled, Phase 3 studies (N = 9439; Population 2). Results: Reductions in HbA1cwith canagliflozin 100 and 300 mg were −0.74% and −0.88%, respectively, in patients from India, and −0.81% and −1.00%, respectively, in the 4 pooled Phase 3 studies. In the Indian subgroup, both canagliflozin doses provided reductions in FPG, body weight, and BP that were consistent with findings in the overall population. The incidence of overall AEs in patients from India was generally similar with canagliflozin 100 and 300 mg and noncanagliflozin. The AE profile in patients from India was generally similar to the overall population, with higher rates of genital mycotic infections and osmotic diuresis–related and volume depletion–related AEs with canagliflozin versus noncanagliflozin. Conclusion: Canagliflozin provided glycemic control, body weight reduction, and was generally well tolerated in patients with T2DM from India