Immunization with Bivalent Flagellin Protects Mice against Fatal Pseudomonas aeruginosa Pneumonia

Pseudomonas aeruginosa lung infections present a major challenge to healthcare systems worldwide because they are commonly associated with high morbidity and mortality. Here, we demonstrate the protective efficacy of type a and b flagellins (bivalent flagellin) against acute fatal pneumonia in mice. Mice immunized intranasally with a bivalent flagellin vaccine were challenged by different flagellated strains of P. aeruginosa in an acute pneumonia model. Besides the protective effect of the vaccine, we further measured the host innate and cellular immunity responses. The immunized mice in our study were protected against both strains. Remarkably, active immunization with type a or b flagellin significantly improved survival of mice against heterologous strain compared to flagellin a or b antisera. We also showed that after an intranasal challenge by P. aeruginosa strain, neutrophils are recruited to the airways of vaccinated mice, and that the bivalent flagellin vaccine was proved to be protective by the generated CD4+IL-17+ Th17 cells. In conclusion, bivalent flagellin vaccine can confer protection against different strains of P. aeruginosa in an acute pneumonia mouse model by eliciting effective cellular and humoral immune responses, including increased IL-17 production and improved opsonophagocytic killing

Prevalence, risk factors, and outcome of myocardial infarction with angiographically normal and near-normal coronary arteries: A systematic review and meta-analysis

Context: Coronary artery diseases are mostly detected using angiographic methods demonstrating arteries status. Nevertheless, Myocardial Infarction (MI) may occur in the presence of angiographically normal coronary arteries. Therefore, this study aimed to investigate the prevalence of MI with normal angiography and its possible etiologies in a systematic review. Evidence Acquisition: In this meta-analysis, the required data were collected from PubMed, Science Direct, Google Scholar, Scopus, Magiran, Scientific Information Database, and Medlib databases using the following keywords: �coronary angiograph�, �normal coronary arteries�, �near-normal coronary arteries�, �heart diseases�, �coronary artery disease�, �coronary disease�, �cardiac troponin I�, �Myocardial infarction�, �risk factor�, �prevalence�, �outcome�, and their Persian equivalents. Then, Comprehensive Meta-Analysis software, version 2 using randomized model was employed to determine the prevalence of each complication and perform the meta-analysis. P values less than 0.05 were considered to be statistically significant. Results: Totally, 20 studies including 139957 patients were entered into the analysis. The patients� mean age was 47.62 � 6.63 years and 64.4 of the patients were male. The prevalence of MI with normal or near-normal coronary arteries was 3.5 (CI = 95, min = 2.2, and max = 5.7). Additionally, smoking and family history of cardiovascular diseases were the most important risk factors. The results showed no significant difference between MIs with normal angiography and 1- or 2-vessel involvement regarding the frequency of major adverse cardiac events (5.4 vs. 7.3, P = 0.32). However, a significant difference was found between the patients with normal angiography and those with 3-vessel involvement in this regard (5.4 vs. 20.2, P < 0.001). Conclusions: Although angiographic studies are required to assess the underlying etiology of MI, physicians facing patients presenting with the clinical features of MI in presence of normal or near-normal coronary arteries should consider the prevalence and risk factors of MI with normal or near-normal coronary arteries. � 2016, Iranian Cardiovascular Research Journal. All rights reserved

Genetic control of protein, oil and fatty acids content under partial drought stress and late sowing conditions in sunflower (Helianthus annuus)

The purpose of the present study was to map quantitative trait locus (QTLs) associated with percentage of seed protein, oil and fatty acids content under different conditions in a population of recombinant inbred lines (RILs) of sunflower. Three independent field experiments were conducted with well-, partial-irrigated and late-sowing conditions in randomized complete block design with three replications. High significant variation among genotypes is observed for the studied traits in all conditions. Several specific and non-specific QTLs for the aforementioned traits were detected. Under late-sowing condition, a specific QTL of palmitic acid content on linkage group 6 (PAC-LS.6) is located between ORS1233 and SSL66_1 markers. Common chromosomic regions are observed for percentage of seed oil and stearic acid content on linkage group 10 (PSO-PI.10 and SAC-WI.10) and 15 (PSO-PI.15 and SAC-LS.15). Overlapping occurs for QTLs of oleic and linoleic acids content on linkage groups 10, 11 and 16. Seven QTLs associated with palmitic, stearic, oleic and linoleic acids content are identified on linkage group 14. These common QTLs are linked to HPPD homologue, HuCL04260C001. Coincidence of the position for some detected QTLs and candidate genes involved in enzymatic and non-enzymatic antioxidants would be useful for the function of the respective genes in fatty acid stability.Key words: Sunflower, quantitative trait locus, simple sequence repeats, oil content, protein content, fatty acids

Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma. In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017. Methods Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex. Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases. We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs. Findings In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9–584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990. Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia. The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically. Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8–7·2] of all deaths), behind cardiovascular diseases and neoplasms. Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578–4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%. However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%). In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD. In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes. Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world. Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions. Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men. Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region. Interpretation Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990. Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.publishedVersio

The burden of disease and injury in Iran 2003

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to estimate the burden of disease and injury in Iran for the year 2003, using Disability-Adjusted Life Years (DALYs) at the national level and for six selected provinces.</p> <p>Methods</p> <p>Methods developed by the World Health Organization for National Burden of Disease (NBD) studies were applied to estimate disease and injury incidence for the calculation of Years of Life Lost due to premature mortality (YLL), Years Lived with Disability (YLD), and DALYs. The following adjustments of the NBD methodology were made in this study: a revised list with 213 disease and injury causes, development of new and more specific disease modeling templates for cancers and injuries, and adjustment for dependent comorbidity. We compared the results with World Health Organization (WHO) estimates for Eastern Mediterranean Region, sub-region B in 2002.</p> <p>Results</p> <p>We estimated that in the year 2003, there were 21,572 DALYs due to all diseases and injuries per 100,000 Iranian people of all ages and both sexes. From this total number of DALYs, 62% were due to disability premature deaths (YLD) and 38% were due to premature deaths (YLL); 58% were due to noncommunicable diseases, 28% – to injuries, and 14% – to communicable, maternal, perinatal, and nutritional conditions. Fifty-three percent of the total number of 14.349 million DALYs in Iran were in males, with 36.5% of the total due to intentional and unintentional injuries, 15% due to mental and behavioral disorders, and 10% due to circulatory system diseases; and 47% of DALYs were in females, with 18% of the total due to mental and behavioral disorders, 18% due to intentional and unintentional injuries, and 12% due to circulatory system diseases. The disease and injury causes leading to the highest number of DALYs in males were road traffic accidents (1.071 million), natural disasters (548 thousand), opioid use (510 thousand), and ischemic heart disease (434 thousand). The leading causes of DALYs in females were ischemic heart disease (438 thousand), major depressive disorder (420 thousand), natural disasters (419 thousand), and road traffic accidents (235 thousand). The burden of disease at the province level showed marked variability. DALY estimates by Iran's NBD study were higher than those for EMR-B by WHO.</p> <p>Conclusion</p> <p>The health and disease profile in Iran has made the transition from the dominance of communicable diseases to that of noncommunicable diseases and road traffic injuries. NBD results are to be used in health program planning, research, and resource allocation and generation policies and practices.</p

Upper critical field, lower critical field and critical current density of FeTe0.60Se0.40 single crystal

The transport and magnetic studies are performed on high quality FeTe0.60Se0.40 single crystals to determine the upper critical fields (Hc2), lower critical field (Hc1) and the Critical current density (Jc). The value of upper critical field Hc2 are very large, whereas the activation energy as determined from the slope of the Arrhenius plots are was found to be lower than that in the FeAs122 superconductor. The lower critical field was determined in ab direction and c direction of the crystal, and was found to have a anisotropy of 'gamma'{=(Hc1//c) / (Hc1//b)} ~ 4. The magnetic isotherms measured up to 12 Tesla shows the presence of fishtail behavior. The critical current densities at 1.8K of the single crystal was found to almost same in both ab and c direction as 1X105 Amp/cm2 in low field regime.Comment: 9 pages, 6 figure

High temperature superconductivity (Tc onset at 34K) in the high pressure orthorhombic phase of FeSe

We have studied the structural and superconducting properties of tetragonal FeSe under pressures up to 26GPa using synchrotron radiation and diamond anvil cells. The bulk modulus of the tetragonal phase is 28.5(3)GPa, much smaller than the rest of Fe based superconductors. At 12GPa we observe a phase transition from the tetragonal to an orthorhombic symmetry. The high pressure orthorhombic phase has a higher Tc reaching 34K at 22GPa.Comment: 15 pages, 4 figure

Individual Assessment of Arteriosclerosis by Empiric Clinical Profiling

BACKGROUND: Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals. We tested how accurately basic clinical data can describe and assess the activity of arteriosclerosis in the individual patient. METHODOLOGY/PRINCIPAL FINDINGS: 269 in-patients who were treated for various conditions at the department of general medicine of an academic tertiary care center were included in a cross-sectional study. Personal history and clinical examination were obtained. When paraclinical tests were performed, the results were added to the dataset. The numerical variables in the clinical examination were statistically compared between patients with proven symptomatic arteriosclerosis (n = 100) and patients who had never experienced cardiovascular events in the past (n = 110). 25 variables were different between these two patient groups and contributed to the disease activity score. The percentile distribution of these variables defined the empiric clinical profile. Anthropometric data, signs of arterial, cardiac and renal disease, systemic inflammation and health economics formed the major categories of the empiric clinical profile that described an individual patient's disease activity. The area under the curve of the receiver operating curve for symptomatic arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated according to the Framingham score. In patients suffering from symptomatic arteriosclerosis, the disease activity score deteriorated more rapidly after two years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex-matched individuals free of cardiovascular events (from 1.09 to 1.19, P = 0.125). CONCLUSIONS/SIGNIFICANCE: Empiric clinical profiling and the disease activity score that are based on accessible, available and affordable clinical data are valid markers for symptomatic arteriosclerosis

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes