25 research outputs found
Cardiovascular risk factors among industrial workers: a cross–sectional study from eastern Nepal
KNN-MDR: a learning approach for improving interactions mapping performances in genome wide association studies
Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection
Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections
Anthropogenic perturbation of the carbon fluxes from land to ocean
A substantial amount of the atmospheric carbon taken up on land through photosynthesis and chemical weathering is transported laterally along the aquatic continuum from upland terrestrial ecosystems to the ocean. So far, global carbon budget estimates have implicitly assumed that the transformation and lateral transport of carbon along this aquatic continuum has remained unchanged since pre-industrial times. A synthesis of published work reveals the magnitude of present-day lateral carbon fluxes from land to ocean, and the extent to which human activities have altered these fluxes. We show that anthropogenic perturbation may have increased the flux of carbon to inland waters by as much as 1.0 Pg C yr-1 since pre-industrial times, mainly owing to enhanced carbon export from soils. Most of this additional carbon input to upstream rivers is either emitted back to the atmosphere as carbon dioxide (~0.4 Pg C yr-1) or sequestered in sediments (~0.5 Pg C yr-1) along the continuum of freshwater bodies, estuaries and coastal waters, leaving only a perturbation carbon input of ~0.1 Pg C yr-1 to the open ocean. According to our analysis, terrestrial ecosystems store ~0.9 Pg C yr-1 at present, which is in agreement with results from forest inventories but significantly differs from the figure of 1.5 Pg C yr-1 previously estimated when ignoring changes in lateral carbon fluxes. We suggest that carbon fluxes along the land–ocean aquatic continuum need to be included in global carbon dioxide budgets.Peer reviewe
Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.
BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised
Estimating Abundance from Counts in Large Data Sets of Irregularly Spaced Plots using Spatial Basis Functions
Avaliação de genótipos de morangueiro quanto à qualidade e potencial de armazenamento
O objetivo deste trabalho foi avaliar a qualidade de cultivares e clones de morangos e o seu potencial de armazenamento sob refrigeração. O delineamento experimental utilizado foi de blocos ao acaso, com quatro repetições de aproximadamente 150g. Os tratamentos consistiram na avaliação de três cultivares e quatro clones, sendo eles: LBH 15.1.Arazá, SGH 140.3. Guenoa, LBF 236.3 Yvapitá, LBG 121.4, LBK 16.1, LBK 35.1 e LBK 28.1. As avaliações foram realizadas na colheita e dez dias após o armazenamento a -0,5ºC, mais dois dias em temperatura de 20ºC. As características avaliadas foram: firmeza de polpa, acidez total titulável, sólidos solúveis totais, relação SST/ATT , ácido ascórbico, podridões e perda de peso. Quanto à qualidade, o cv. Guenoa destaca-se pelo baixo teor de acidez e altos teores de SST e ácido ascórbico, pela alta relação SST/ATT e, também, apresenta melhor conservação, com baixa ocorrência de podridões durante o armazenamento. O cultivar LBF 236.3 Yvapitá e o clone LBK 28.1 apresentam os menores teores de vitamina C e ratio, o que compromete sua qualidade, bem como menor firmeza de polpa e maior susceptibilidade a podridões, apresentando menor potencial de conservação. Os cultivares e clones que apresentaram melhor qualidade na colheita também apresentaram melhor conservação pós-colheita