385 research outputs found

    Validation and implementation of a diagnostic algorithm for DNA Detection of Bordetella pertussis, B. parapertussis, and B-holmesii in a Pediatric Referral Hospital in Barcelona, Spain

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    This study aimed to validate a comprehensive diagnostic protocolbased on real-time PCR for the rapid detection and identification ofBordetella per-tussis,Bordetella parapertussis, andBordetella holmesii, as well as its implementationin the diagnostic routine of a reference children’s hospital. The new algorithm in-cluded a triplex quantitative PCR (qPCR) targeting IS481gene (inB. pertussis,B. hol-mesii, and someBordetella bronchisepticastrains), pIS1001(B. parapertussis-specific)andrnaseP as the human internal control. Two confirmatory singleplex tests forB.pertussis(ptxA-Pr) andB. holmesii(hIS1001) were performed if IS481was positive. An-alytical validation included determination of linear range, linearity, efficiency, preci-sion, sensitivity, and a reference panel with clinical samples. Once validated, the newalgorithm was prospectively implemented in children with clinical suspicion ofwhooping cough presenting to Hospital Sant Joan de Deu (Barcelona, Spain) over12 months. Lower limits of detection obtained were 4.4, 13.9, and 27.3 genomicequivalents/ml of sample for IS481(onB. pertussis), pIS1001and hIS1001, and 777.9forptxA-Pr. qPCR efficiencies ranged from 86.0% to 96.9%. Intra- and interassay vari-abilities were 3% and 5%, respectively. Among 566 samples analyzed,B. pertus-sis,B. holmesii, andB. parapertussiswere detected in 11.1%, 0.9% (only in females 4 years old), and 0.2% of samples, respectively. The new algorithm proved to be auseful microbiological diagnostic tool for whooping cough, demonstrating a low rateof other non-pertussis Bordetellaspecies in our surveilled areaPeer ReviewedPostprint (author's final draft

    Mitochondria and the NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis

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    Alcoholic (ASH) and nonalcoholic steatohepatitis (NASH) are advanced stages of fatty liver disease and two of the most prevalent forms of chronic liver disease. ASH and NASH are associated with significant risk of further progression to cirrhosis and hepatocellular carcinoma (HCC), the most common type of liver cancer, and a major cause of cancer-related mortality. Despite extensive research and progress in the last decades to elucidate the mechanisms of the development of ASH and NASH, the pathogenesis of both diseases is still poorly understood. Mitochondrial damage and activation of inflammasome complexes have a role in inducing and sustaining liver damage. Mitochondrial dysfunction produces inflammatory factors that activate the inflammasome complexes. NLRP3 inflammasome (nucleotide-binding oligomerization domain-like receptor protein 3) is a multiprotein complex that activates caspase 1 and the release of pro-inflammatory cytokines, including interleukin-1? (IL-1?) and interleukin-18 (IL-18), and contributes to inflammatory pyroptotic cell death. The present review, which is part of the issue "Mitochondria in Liver Pathobiology", provides an overview of the role of mitochondrial dysfunction and NLRP3 activation in ASH and NASH

    Relato de una experiencia: La Maranya, una escuela de democracia ciudadana con jóvenes

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    El siguiente artículo busca difundir una experiencia asociativa enmarcada por la autogestión juvenil en el municipio de Benicàssim. Contamos cómo nace el centro cívico La Maranya y cuál es la ideología desde la que trabaja. La acción de esta asociación surge a partir del trabajo en el tiempo libre y de ocio como herramienta educativa. El centro parte de la participación cívica y democrática, el aprendizaje directo y el interés por los problemas de la sociedad para generar una escuela ciudadana de convivencia igualitaria. Este espacio trabaja con las jóvenes y los jóvenes como ciudadanas y ciudadanos activos conectados intergeneracionalmente con otros colectivos que lo conforman dentro de unos valores de progreso y participación social.Aquest article pretén difondre una experiència associativa emmarcada per l’autogestió juvenil al municipi de Benicàssim. Expliquem el naixement del centre cívic La Maranya i quina és la ideologia des de la qual treballa. L’acció d’aquesta associació sorgeix arran del treball en el temps lliure i d’esplai com a eina educativa. El centre parteix de la participació cívica i democràtica, de l’aprenentatge directe i l’interès pels problemes de la societat per a generar una escola ciutadana de convivència igualitària. L’espai treballa amb les persones joves com a ciutadanes i ciutadans actius connectats intergeneracionalment amb altres col·lectius que el conformen dins de valors de progrés i de participació social.The following article reports on an associational experience within the framework of young people’s self-management in the town of Benicàssim. We describe how La Maranya Civic Centre came into being and the ideology it is grounded on. The association’s action is based on using free time and leisure as an educational tool. The Civic Centre operates on the basis of democratic participation, non-formal learning and interest in society’s problems to generate a citizens’ school for egalitarian coexistence. The centre treats young people as active citizens who participate as equals with other age groups and associations, thus providing a context that fosters and promotes values associated with progress and democratic participation

    Binning effects on in-situ raindrop size distribution measurements

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    This paper investigates the binning effects on drop size distribution (DSD) measurements obtained by Joss-Waldvogel disdrometer (JWD), Precipitation Occurrence Sensor System (POSS), Thies disdrometer (Thies), Parsivel OTT disdrometer, two-dimensional video disdrometer (2DVD) and optical spectro-pluviometer (OSP) instruments, therefore the evaluation comprises non-regular bin sizes and the effect of minimum and maximum measured sizes of drops. To achieve this goal, 2DVD measurements and simulated gamma size distributions were considered. The analysis of simulated gamma DSD binned according each instrument was performed to understand the role of discretisation and truncation effects together on the integral rainfall parameters and estimators of the DSD parameters. In addition, the drop-by-drop output of the 2DVD is binned to simulate the raw output of the other disdrometers which allowed us estimate sampling and binning effects on selected events from available dataset. From simulated DSD it has been found that binning effects exist in integral rainfall parameters and in the evaluation of DSD parameters of a gamma distribution. This study indicates that POSS and JWD exhibit underestimation of concentration and mean diameter due to binning. Thies and Parsivel report a positive bias for rainfall and reflectivity (reaching 5% for heavy rainfall intensity events). Regarding to DSD parameters, distributions of estimators for the shape and scale parameters were analyzed by moment, truncated moment and maximum likelihood methods. They reported noticeable differences between instruments for all methodologies of estimation applied. The measurements of 2DVD allow sampling error estimation of instruments with smaller capture areas than 2DVD. The results show that the instrument differences due to sampling were a~relevant uncertainty but that concentration, reflectivity and mass-weighted diameter were sensitive to binning

    Mapping spectroscopic uncertainties into prospective methane retrieval errors from Sentine-5 and its precursor

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    Sentinel-5 (S5) and its precursor (S5P) are future European satellite missions aiming at global monitoring of methane (CH4) column average dry air mole fractions (XCH4). The spectrometers to be deployed on-board the satellites record spectra of sunlight backscattered from the Earth\u27s surface and atmosphere. In particular, they exploit CH4 absorption in the shortwave infrared spectral range around 1.65 µm (S5 only) and 2.35 µm (both, S5 and S5P) wavelength. Given an accuracy goal of better than 2% for XCH4 to be delivered on regional scales, assessment and reduction of potential sources of systematic error such as spectroscopic uncertainties is crucial. Here, we investigate how spectroscopic errors propagate into retrieval errors on the global scale. To this end, absorption spectra of a ground-based Fourier Transform Spectrometer (FTS) operating at very high spectral resolution serve as estimate for the quality of the spectroscopic parameters. Feeding the FTS fitting residuals as a perturbation into a global ensemble of simulated S5 and S5P-like spectra at relatively low spectral resolution, XCH4 retrieval errors exceed 1% in large parts of the world and show systematic correlations on regional scales, calling for improved spectroscopic parameters

    Hypoxia signaling and cholesterol/steroidogenic acute regulatory protein 1 axis: interplay and role in alcohol and non-alcohol-related liver diseases

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    Metabolic zonation in the liver carries out the maintenance of organ and body homeostasis. Hypoxia is an inherent physiological feature of the liver and contributes to the zonal properties of the hepatic parenchyma. As a master regulator of hypoxia, the transcription factor hypoxia-inducing factor (HIF) is stabilized primarily by oxygen availability, and it is thought to contribute to steatohepatitis due to alcohol-related (ASH) and non-alcohol-related liver disease (NASH). Cholesterol has emerged as an important player in both diseases, and hypoxia increases hepatic cholesterol levels. Steroidogenic acute regulatory protein 1 (STARD1) is a mitochondrial outer membrane protein that transfers cholesterol to mitochondrial inner membrane for metabolic processing and acts as the rate-limiting step in the alternative pathway of bile acid synthesis in hepatocytes. STARD1 expression increases in ASH and NASH and determines the accumulation of cholesterol in mitochondria, which impacts the physico-chemical mitochondrial membranes properties and as a consequence impairs the activity of specific mitochondrial solute carriers, such as the 2-oxoglutarate carrier (2-OGC), limiting the exchange between cytosolic glutathione and mitochondrial 2-oxoglutarate (2-OG). Although HIF-1 is stabilized in hypoxia largely due to the requirement of prolylhydroxylases (PHDs) for oxygen to signal HIF degradation, PHDs are also dependent on 2-OG, and therefore it is conceivable that impairment of 2-OGC by STARD1-mediated cholesterol accumulation may contribute to HIF-1 stabilization due in part to decreased availability of cytosolic 2-OG. In this perspective, this review explores the interplay between HIF-1 stabilization and STARD1 induction and the potential contribution of this functional relationship to ASH and NASH
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