Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Forouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. LANCET. 2016;388(10053):1659-1724.Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd

Detection of Critical Genes Associated with Overall Survival (OS) and Progression-Free Survival (PFS) in Reconstructed Canine B-Cell Lymphoma Gene Regulatory Network (GRN)

<p>Canine B-cell lymphoma GRN was reconstructed from gene expression data in the STRING and MiMI databases. Critical genes of networks were identified and correlations of critical genes with overall survival (OS) and progression-free survival (PFS) were evaluated. Significant changes were detected in the expressions of <i>GLUL, CD44, CD79A, ARF3, FOS, BLOC1S1, FYN, GZMB, GALNT3, IFI44, CD3G, GNG2, ESRP1</i>, and <i>CCND1</i> in the STRING network and of <i>PECAM1, GLUL, CD44, GDI1, E2F4, TLE1, CD79A, UCP2, CCND1, FYN, RHOQ, BIN1</i>, and <i>A2M</i> in the MiMI network. Final survival analysis highlighted <i>CCND1</i> and <i>FOS</i> as genes with significant correlations with OS and PFS.</p

Comparison Between Transepicardial Cell Transplantations: Autologous Undifferentiated Versus Differentiated Marrow Mesenchymal Stem Cells

Background: Marrow-derived mesenchymal stem cells (MSCs) have been heralded as a source of great promise for the regeneration of the infarcted heart. There are no clear data as to whether or not in vitro differentiation of MSCs into major myocardial cells can increase the beneficial effects of MSCs. The aim of this study was to address this issue.Methods: To induce MSCs to transdifferentiate into cardiomyocytes and endothelial cells, 5-Azacytidine and vascular endothelial growth factor (VEGF) were used, respectively. Myocardial infarction in rabbits was generated by ligating the left anterior descending coronary artery. The animals were divided into three experimental groups: I) control group, II) undifferentiated mesenchymal stem cell transplantation group, and III) differentiated mesenchymal stem cell transplantation group. The three groups received peri-infarct injections of culture media, autologous undifferentiated MSCs, and autologous differentiated MSCs, respectively. Echocardiography and pathology were performed in order to search for improvement in the cardiac function and reduction in the infarct size. Results: Improvements in the left ventricular function and reductions in the infarcted area were observed in both cell transplanted groups (Groups II and III) to the same degree. Conclusions: There is no need for prior differentiation induction of marrow-derived MSCs before transplantation, and peri-infarct implantation of MSCs can effectively reduce the size of the infarct and improve the cardiac function

Molecular and serological detection of Ehrlichia canis in naturally exposed dogs in Iran: an analysis on associated risk factors

The general aim of this study, which was conducted for the first time in Iran, was to evaluate the seroprevalence and geographical distribution of Ehrlichia canis in a dog population in Iran, followed by molecular confirmation using PCR and sequencing. Blood samples were collected from 240 dogs in different areas of Alborz and Tehran Provinces and initially analyzed using the immunofluorescent antibody (IFA) test to detect anti-Ehrlichia canis IgG antibodies. Subsequently, nested PCR was performed based on a fragment of the 16S rRNA gene of E. canis on serologically positive samples. The results showed that 40/240 dogs (16.6%) presented anti-Ehrlichia canis IgG antibodies and that nine of the blood samples from the 40 seropositive dogs (22.5%) contained E. canis DNA, which was confirmed by sequencing. The seroprevalence of E. canis tended to be higher in purebred, one to three-year-old male dogs living in the Plain zone, in rural areas; however, this difference was not statistically significant