CAFFEINEAS A PROMISING ANTIFBROTIC AGENT AGAINST CCL4-INDUCED LIVER FIBROSIS

Objective: Hepatic fibrosis is a wound-healing process in the liver with chronic injury and is characterized by an excess production and deposition of extracellular matrix (ECM) components. Our aim is to investigate the hepatoprotective effects of caffeine against CCL4-induced liver fibrosis in rats and to be compared with the reference standard N-acetylcysteine (NAC).Methods: Rats were divided into 5 groups (n=8), the 1st group served as normal control, the 2nd group received corn oil, the 3rd group is a fibrosis control and the remaining two groups received in addition to CCL4, NAC (150 mg/kg/day) as a reference treatment and caffeine (15 mg/kg/day). At the end of experimental period the following parameters were measured, specific fibrosis biomarkers [hepatic transforming growth factor β1(TGF-β1) and hepatic hydroxyproline (HYP)], liver function biomarkers [serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin and albumin], lipid profile [serum triglycerides, total cholesterol, low density lipoprotein cholesterol (LDL-Ch) and high density lipoprotein cholesterol (HDL-Ch)], inflammatory biomarkers [serum tumor necrosis factor alpha (TNF-α), hepatic myeloperoxidase (MPO)], oxidative stress biomarkers [hepatic malondialdehyde (MDA), glutathione (GSH) and catalase (CAT)], relative liver body weight and liver histopathological study.Results: Caffeine significantly improved all the aforementioned biochemical parameters and liver sections obtained from this group showed prominent histopathological improvement.Conclusion: Caffeine hepatoprotective effects may be due to modulation of the fibrous scar formation, Improvement of liver function, Anti-inflammatory and antioxidant potentials

Addressing the challenges of ECMO simulation

This document is the Accepted Manuscript. The final, definitive version of this paper has been published in Perfusion, May 2018, published by SAGE Publishing, All rights reserved.Introduction/Aim: The patient’s condition and high-risk nature of extracorporeal membrane oxygenation (ECMO) therapy force clinical services to ensure clinicians are properly trained and always ready to deal effectively with critical situations. Simulation-based education (SBE), from the simplest approaches to the most immersive modalities, helps promote optimum individual and team performance. The risks of SBE are negative learning, inauthenticity in learning and over-reliance on the participants’ suspension of disbelief. This is especially relevant to ECMO SBE as circuit/patient interactions are difficult to fully simulate without confusing circuit alterations. Methods: Our efforts concentrate on making ECMO simulation easier and more realistic in order to reduce the current gap there is between SBE and real ECMO patient care. Issues to be overcome include controlling the circuit pressures, system failures, patient issues, blood colour and cost factors. Key to our developments are the hospital-university collaboration and research funding. Results: A prototype ECMO simulator has been developed that allows for realistic ECMO SBE. The system emulates the ECMO machine interface with remotely controllable pressure parameters, haemorrhaging, line chattering, air bubble noise and simulated blood colour change. Conclusion: The prototype simulator allows the simulation of common ECMO emergencies through innovative solutions that enhance the fidelity of ECMO SBE and reduce the requirement for suspension of disbelief from participants. Future developments will encompass the patient cannulation aspect.Peer reviewe

12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase

The purpose of the current study was to evaluate the effect of 12/15- lipoxygenase (12/15-LOX) metabolites on retinal endothelial cell (REC) barrier function. FITC-dextran flux across the REC monolayers and electrical cell-substrate impedance sensing (ECIS) were used to evaluate the effect of 12- and 15-hydroxyeicosatetreanoic acids (HETE) on REC permeability and transcellular electrical resistance (TER). Effect of 12- or 15-HETE on the levels of zonula occludens protein 1 (ZO-1), reactive oxygen species (ROS), NOX2, pVEGF-R2 and pSHP1 was examined in the presence or absence of inhibitors of NADPH oxidase. In vivo studies were performed using Ins2Akita mice treated with or without the 12/15-LOX inhibitor baicalein. Levels of HETE and inflammatory mediators were examined by LC/MS and Multiplex Immunoassay respectively. ROS generation and NOX2 expression were also measured in mice retinas. 12- and 15- HETE significantly increased permeability and reduced TER and ZO-1expression in REC. VEGF-R2 inhibitor reduced the permeability effect of 12-HETE. Treatment of REC with HETE also increased ROS generation and expression of NOX2 and pVEGF-R2 and decreased pSHP1 expression. Treatment of diabetic mice with baicalein significantly decreased retinal HETE, ICAM-1, VCAM-1, IL-6, ROS generation, and NOX2 expression. Baicalein also reduced pVEGF-R2 while restored pSHP1 levels in diabetic retina. Our findings suggest that 12/15-LOX contributes to vascular hyperpermeability during DR via NADPH oxidase dependent mechanism which involves suppression of protein tyrosine phosphatase and activation of VEGF-R2 signal pathway.Qatar National Research Fund (NPRP 4 - 1046 - 3 -284), American Heart Association (AHA00104) and Vision Discovery Institute (VDI002010) and Bridge Fund (BFP00018) from the Georgia Health Sciences University.Scopu

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18 : a geospatial modelling study

Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels.Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km x 5 km resolution in 98 LMICs based on 2.1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution.Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205000 (95% uncertainty interval 147000-257000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution.Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Isolation and characterization of cellulolytic Bacillus licheniformis from compost

Eight cellulose degrading bacteria were isolated from compost and were identified as Bacillus licheniformis by 16S rRNA sequencing. Among the eight isolates, Bacillus licheniformis B4, B7 and B8 showed the highest cellulase activity. B. licheniformis B4 and B8 showed the maximum cellulase activity during the stationary phase of growth; but for B7, the maximum activity of cellulase was observed during the log phase. Reducing sugar released in the media, increased with increasing cellulase activity for all the three isolates. Significant correlation was observed between cellulase activity and protein content. The crude cellulase from B7 strain showed activity towards carboxymethyl cellulose and filter paper, but there was no detectable activity towards p-nitrophenyl- β-Dglucopyranoside (PNPG). The crude cellulase of B. licheniformis B7 exhibited maximum activity at 50°C and at pH 6 to 7.Keywords: Bacillus licheniformis, 16S rRNA, cellulase, reducing sugar, compost, viscosit

Impacts of smoking & ocular activity on Behcet disease & normal control by optical coherence tomography angiography (OCTA) in Upper Egypt

Retinal vasculitis and vein occlusions are common causes of serious visual loss in Behcet’s disease. The aim of the current work was the comparison of the OCTA results of BU cases, BD without uveitis cases &normal control was further subdivided to smokers &non-smokers to permit us to recognize retinal micro-circulation variations at the macular level in BU cases even in the nonattendance of preceding angiographic diagnosing of vasculitis & impact of smoking on BD clinical results of Behcet uveitis(BU), Behcet disease with no uveitis cases &normal control by the following parameters; Vessel density of macular area (VD) & foveal Avascular zone (FAZ) using OCTA. The conclusion of this study shows reduction of vessel density of macular area in Behcet uveitis (BU) rather than Behcet disease without uveitis &normal control & Enlarged FAZ in BU rather than BD without uveitis & normal control. The study results revealed areas of hypoperfusion of macular area even in BD without clinical signifacnce. Hazards of smoking on uveitis cases . There is a need to larger samples & lack of stable treatment protocols