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 and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions