Global, regional, and national burden of other musculoskeletal disorders, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background Musculoskeletal disorders include more than 150 different conditions affecting joints, muscles, bones, ligaments, tendons, and the spine. To capture all health loss from death and disability due to musculoskeletal disorders, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) includes a residual musculoskeletal category for conditions other than osteoarthritis, rheumatoid arthritis, gout, low back pain, and neck pain. This category is called other musculoskeletal disorders and includes, for example, systemic lupus erythematosus and spondylopathies. We provide updated estimates of the prevalence, mortality, and disability attributable to other musculoskeletal disorders and forecasted prevalence to 2050. Methods Prevalence of other musculoskeletal disorders was estimated in 204 countries and territories from 1990 to 2020 using data from 68 sources across 23 countries from which subtraction of cases of rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout from the total number of cases of musculoskeletal disorders was possible. Data were analysed with Bayesian meta-regression models to estimate prevalence by year, age, sex, and location. Years lived with disability (YLDs) were estimated from prevalence and disability weights. Mortality attributed to other musculoskeletal disorders was estimated using vital registration data. Prevalence was forecast to 2050 by regressing prevalence estimates from 1990 to 2020 with Socio-demographic Index as a predictor, then multiplying by population forecasts. Findings Globally, 494 million (95% uncertainty interval 431–564) people had other musculoskeletal disorders in 2020, an increase of 123·4% (116·9–129·3) in total cases from 221 million (192–253) in 1990. Cases of other musculoskeletal disorders are projected to increase by 115% (107–124) from 2020 to 2050, to an estimated 1060 million (95% UI 964–1170) prevalent cases in 2050; most regions were projected to have at least a 50% increase in cases between 2020 and 2050. The global age-standardised prevalence of other musculoskeletal disorders was 47·4% (44·9–49·4) higher in females than in males and increased with age to a peak at 65–69 years in male and female sexes. In 2020, other musculoskeletal disorders was the sixth ranked cause of YLDs globally (42·7 million [29·4–60·0]) and was associated with 83 100 deaths (73 600–91 600). Interpretation Other musculoskeletal disorders were responsible for a large number of global YLDs in 2020. Until individual conditions and risk factors are more explicitly quantified, policy responses to this burden remain a challenge. Temporal trends and geographical differences in estimates of non-fatal disease burden should not be overinterpreted as they are based on sparse, low-quality data.publishedVersio

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

The effect of Allium sativum on ischemic preconditioning and ischemia reperfusion induced cardiac injury

In the present study, the effect of garlic (Allium sativum) extract on ischemic preconditioning and ischemia-reperfusion induced cardiac injury has been studied. Hearts from adult albino rats of Wistar strain were isolated and immediately mounted on Langendorff's apparatus for retrograde perfusion. After 15 minutes of stabilization, the hearts were subjected to four episodes of 5 min ischemia, interspersed with 5 min reperfusion (to complete the protocol of ischemic preconditioning), 30 min global ischemia, followed by 120 min of reperfusion. In the control and treated groups, respective interventions were given instead of ischemic preconditioning. The magnitude of cardiac injury was quantified by measuring Lactate Dehydrogenase and creatine kinase concentration in the coronary effluent and myocardial infarct size by macroscopic volume method. Our study demonstrates that garlic extract exaggerates the cardio protection offered by ischemic preconditioning and per se treatment with garlic extract also protects the myocardium against ischemia reperfusion induced cardiac injury

Electrochemical treatment of high strength chrome bathwater: A comparative study for best-operating conditions

In this study, high strength chromium (1500 ​ppm) wastewater was treated by electrochemical and chemical precipitation. Preliminary experiments using synthetic wastewater were carried out to optimize the process parameters viz. pH, current density and treatment time by systematically varying these variables as per response surface methodology (RSM) approach. The results showed that 97.5% chromium removal efficiency was achieved under optimized process conditions, i.e. pH 5, current density 68 A/m2 and treatment time 17 ​min. The electrolyte concentration beyond 4 ​g/L does not significantly improve chromium removal efficiency. The optimized process conditions from simulated solution were used to treat real chrome bathwater, but due to the highly acidic nature of the chrome bath, negligible chromium removal was obtained. Thus, two industrial wastewater management approaches were used to improve the chromium removal efficiency (i) dilution of the chrome bathwater (ii) chemical precipitation before electrocoagulation. Electrocoagulation treatment of five-fold diluted chrome bathwater has 99.9% chromium removal efficiency in 55 ​min of treatment time consuming specific energy consumption (SEC) of 10.3 ​KWh/kg of chromium. By integration of chemical precipitation and electrochemical treatment, the chromium removal efficiency of 97.3% was observed in 240 ​min of treatment time with SEC of 27.3 ​kWh/kg of chromium. Integration of reduction-precipitation before electrochemical treatment is another choice, in contrast, to sample dilution with an option for retrofitting of existing treatment schemes

Role of water in cyclooxygenase catalysis and design of anti-inflammatory agents targeting two sites of the enzyme

Abstract While designing the anti-inflammatory agents targeting cyclooxygenase-2 (COX-2), we first identified a water loop around the heme playing critical role in the enzyme catalysis. The results of molecular dynamic studies supported by the strong hydrogen-bonding equilibria of the participating atoms, radical stabilization energies, the pKa of the H-donor/acceptor sites and the cyclooxygenase activity of pertinent muCOX-2 ravelled the working of the water–peptide channel for coordinating the flow of H·/electron between the heme and Y385. Based on the working of H·/electron transfer channel between the 12.5 Å distant radical generation and the radical disposal sites, a series of molecules was designed and synthesized. Among this category of compounds, an appreciably potent anti-inflammatory agent exhibiting IC50 0.06 μM against COX-2 and reversing the formalin induced analgesia and carageenan induced inflammation in mice by 90% was identified. Further it was revealed that, justifying its bidentate design, the compound targets water loop (heme bound site) and the arachidonic acid binding pockets of COX-2

<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Effect of <i style="mso-bidi-font-style:normal">Aegle marmelos</i> (L.) Correa on alloxan induced early stage diabetic nephropathy in rats</span>

464-469Diabetic nephropathy (DN) has a complex pathogenesis and poor prognosis due to the lack of therapeutic interventions. The present study investigates the effect of A. marmelos leaf extract (AME) on early alloxan induced DN. The treatment with AME was found to significantly decrease the fasting blood sugar, total cholesterol, blood urea, creatinine and renal TBARS and increased the levels of renal reduced glutathione and catalase significantly as compared to the diabetic control group. The maximum dose-dependent protection was observed at a dose of 200 mg kg-1. Histological examination revealed marked reversal of the morphological derangements with AME treatment as indicated by a decrease in glomerular expansion, tubular dilatation and inflammatory cells. The present results conclude that AME treatment has a significant ameliorative effect on early changes induced in the kidneys by alloxan and improves the outcome of DN