Brain MRI: a useful tool for screening of hypertensive patients for silent cerebro-vascular damage

Background: Worldwide hypertension is an important public-health challenge because of its high frequency and concomitant risks of cardiovascular, renal, cerebrovascular disease and death. Current guidelines for the management of hypertension mainly recommend the search for preclinical damage to the heart and kidneys. However, extending this search to other organs, for instance the brain, might improve risk stratification, might optimize antihypertensive therapy and might, in the end help to further reduce the burden of disease attributable to hypertension.Methods: 84 consecutive hypertensive patients with no target organ damage were enrolled in study to find out silent brain damage over a period of one year.Results: Mean body mass index (BMI) of the study population was 28.4±2.5 kg/m2 (range 23.2 to 35.3kg/m2). 33 (39.3%) subjects had white matter lesions. 13 (15.47%) study subjects were found to have vascular changes which included micro angiopathic changes, infarcts and reduced/slow blood flow. 33 (39.3%) subjects were found to have normal brain MRI in the study. Early brain MRI was found to be beneficial in patients who had uncontrolled blood pressure either due to lack of treatment or irregular use of anti-hypertensive treatment. This was true for every age group in general and particularly in subjects above the age of 50 years.Conclusions: The screening of hypertensive patients for silent cerebrovascular damage with brain MRI may be useful in stratifying the risk of future cerebrovascular disease

Clinical profile of snake bite patients in tertiary care hospital in Himachal Pradesh: a prospective study

Background: To study clinical profile of snake bite patients in tertiary care hospital in Indra Gandhi Medical College at Shimla, Himachal Pradesh of North India.Methods: Hospital based prospective observational study was conducted in the Department of Medicine, for the duration of one year from 1st June2013 to 31st May 2014.Results: A total of 78 patients were admitted with mean age of 38.46 years with male to female ratio of 1:1.6. Seasonal variation with peak incidence during rainy season was seen. Most common snake identified was green coloured and peak timing of snake bite was between 07:00am-04:00pm. There was delay in admission of more than 6 hours in 66.67% of cases. Hemotoxicity was predominant manifestation seen in 62.82% of cases and persistence of coagulopathy was most common complication (51.02%) despite giving optimal ASV. There was paucity in ASV administration seen in only 59.46% of referred patients. Mean ASV vials used were 23.41 vials ±8.72 vials.Conclusions: Mass education is required at both general population and health professional levels to improve snake bite management and monovalent ASV against Green pit viper is more practical option to manage cases in this region

Computerized tomography based evaluation of level I and II axillary lymph nodes by high conventional tangential fields in carcinoma breast

Background: Axillary radiation and surgery have provided equivalent local control in early breast cancer patients. It is believed that tangential field (TF) radiation that was used to treat the breast coincidently delivered radiation treatment to the lower axilla and eradicated the disease. In the era of CT-based three dimensional- (3D) radiotherapy planning, however concerns have been raised about the adequacy of coverage of the axillary levels in the tangential fields. In this study, author evaluated the coverage of the axillary nodal levels I and II using high conventional tangential fields in patients with or without axillary dissection.Methods: A prospective study was conducted which included 18 cases for a period of one year, radiation therapy was planned to the chest wall or whole breast by using the high conventional tangential field using 2D radiation portals. Central lung distance (CLD) and the distance of superior border was measured form the head of the humerus and were recorded. CECT chest was done in the same position alike during conventional simulation. All the images were shifted to the treatment planning system. The Contouring of Axillary lymph nodes level I and II was done on Oncentra contouring software.Results: The coverage of the axillary nodes was not related to central lung distance (CLD). However, some with CLD of 1cm had more coverage of the level I nodes than with CLD of 2 cm and the maximum CLD in the field was 2.5 cm. Of the 18 patients in the study, 13 patients had 2 cm did not have adequate coverage of level II axillary LN’s.Conclusions: The distance of the cranial border of the tangent portal from the head of the humerus shows a relationship with coverage of level II nodes cranially. As the distance decreases the coverage of level II nodes cranially keeps increasing. In majority of the patients a distance of 2 cm or less than 2 cm ensured good coverage of level II nodes cranially. Similarly, no correlation was found between volumetric coverage of the axillary nodes with central lung distance

Microbial beta glucosidase enzymes: recent advances in biomass conversation for biofuels application

The biomass to biofuels production process is green, sustainable, and an advanced technique to resolve the current environmental issues generated from fossil fuels. The production of biofuels from biomass is an enzyme mediated process, wherein β-glucosidase (BGL) enzymes play a key role in biomass hydrolysis by producing monomeric sugars from cellulose-based oligosaccharides. However, the production and availability of these enzymes realize their major role to increase the overall production cost of biomass to biofuels production technology. Therefore, the present review is focused on evaluating the production and efficiency of β-glucosidase enzymes in the bioconversion of cellulosic biomass for biofuel production at an industrial scale, providing its mechanism and classification. The application of BGL enzymes in the biomass conversion process has been discussed along with the recent developments and existing issues. Moreover, the production and development of microbial BGL enzymes have been explained in detail, along with the recent advancements made in the field. Finally, current hurdles and future suggestions have been provided for the future developments. This review is likely to set a benchmark in the area of cost effective BGL enzyme production, specifically in the biorefinery area

Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD

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