50 research outputs found

    TRAFAIR: Análisis de los flujos de tráfico para mejorar la calidad del aire urbano

    Get PDF
    El proyecto TRAFAIR reúne a 9 socios de España e Italia para desarrollar servicios innovadores empleando datos de calidad del aire, condiciones meteorológicas y de flujos de tráfico, en beneficio tanto de los ciudadanos, como de las autoridades responsables de la toma de decisiones que afectan a la calidad del aire

    Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation

    Get PDF
    Bile acid; Inflammation; Oncostatin MÀcid biliar; Inflamació; Oncostatina MÁcido biliar; Inflamación; Oncostatina MBile acid (BA) synthesis from cholesterol by hepatocytes is inhibited by inflammatory cytokines. Whether liver inflammation also affects BA side chain shortening and conjugation was investigated. In human liver cell lines (IHH, HepG2, and HepaRG), agonists of nuclear receptors including the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptors (PPARs) did not affect the expression of BA-related peroxisomal enzymes. In contrast, hepatocyte nuclear factor 4α (HNF4α) inhibition down-regulated acyl-CoA oxidase 2 (ACOX2). ACOX2 was repressed by fibroblast growth factor 19 (FGF19), which was prevented by extracellular signal-regulated kinase (ERK) pathway inhibition. These changes were paralleled by altered BA synthesis (HPLC-MS/MS). Cytokines able to down-regulate cholesterol-7α-hydroxylase (CYP7A1) had little effect on peroxisomal enzymes involved in BA synthesis except for ACOX2 and bile acid-CoA:amino acid N-acyltransferase (BAAT), which were down-regulated, mainly by oncostatin M (OSM). This effect was prevented by Janus kinase (JAK) inhibition, which restored BA side chain shortening and conjugation. The binding of OSM to the extracellular matrix accounted for a persistent effect after culture medium replacement. In silico analysis of four databases (n = 201) and a validation cohort (n = 90) revealed an inverse relationship between liver inflammation and ACOX2/BAAT expression which was associated with changes in HNF4α levels. In conclusion, BA side chain shortening and conjugation are inhibited by inflammatory effectors. However, other mechanisms involved in BA homeostasis counterbalance any significant impact on the serum BA profile.This study was supported by the CIBERehd (EHD15PI05/2016) and Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819, PI20/00189, and PI20/01663 co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); Junta de Castilla y Leon (SA074P20); Fundació Marato TV3 (Ref. 201916/31), Spain; AECC Scientific Foundation (2017/2020), Spain; Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of Wuerzburg, Germany (Project A-E-384 to H.M.H.); grants PID2019-111669-RB-I00, PID2020-115055RB-I00 from Agencia Estatal de Investigación (AEI), Spain; the AGAUR of the Generalidad de Cataluña SGR-2017-1112, Spain; and European Cooperation in Science & Technology (COST) Action CA17112. R.E.E was recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). J.A. was recipient of a grant from Fundación Echebano (2020–2022)

    Premature ventricular contractions in patients with an implantable cardioverter defibrillator cardiac resynchronization therapy device: Results from the UMBRELLA registry

    Get PDF
    BACKGROUND: Premature ventricular contractions (PVC) are known to reduce the percentage of biventricular (BiV) pacing in patients with cardiac resynchronization (CRT), decreasing the clinical response. The aim of this study was to evaluate the prevalence of a high PVC burden, as well as therapeutic action (pharmacotherapy, catheter ablation or device programming), in a large CRT implantable-defibrillator (CRT-D) population. METHODS: Patients with a CRT-D device from the UMBRELLA multicenter prospective remote monitoring registry were included. The PVC count was collected from each remote monitoring transmission. Patients were divided into two high (>/=1 transmission >/=200/>/=400 PVC/h, respectively) and one low (all transmissions /=200/>/=400 PVC/h, respectively). The majority of patients in the high PVC groups were not treated (61 [79%] and 32 [74%], respectively. Considering the untreated patients in the high PVC groups, median PVC/h was 199 (interquartile range [IQR]: 196) and 271 (IQR: 330), respectively. The PVC burden (proportion of time with PVC/h >/= 200/>/=400) was 40% (IQR 70) and 29% (IQR 59), respectively. CONCLUSION: A significant proportion of CRT-D patients presented a high PVC count, however, few received treatment. In the untreated patients with a high PVC count, the PVC burden during follow-up varied substantially. Several consecutive recordings of a high PVC count should be warranted before considering therapeutic action such as catheter ablation
    corecore