BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages

In response to environmental stimuli, macrophages change their nutrient consumption and undergo an early metabolic adaptation that progressively shapes their polarization state. During the transient, early phase of pro-inflammatory macrophage activation, an increase in tricarboxylic acid (TCA) cycle activity has been reported, but the relative contribution of branched-chain amino acid (BCAA) leucine remains to be determined. Here, we show that glucose but not glutamine is a major contributor of the increase in TCA cycle metabolites during early macrophage activation in humans. We then show that, although uptake of BCAAs is not altered, their transamination by BCAT1 is increased following 8 h lipopolysaccharide (LPS) stimulation. Of note, leucine is not metabolized to integrate into the TCA cycle in basal or stimulated human macrophages. Surprisingly, the pharmacological inhibition of BCAT1 reduced glucose-derived itaconate, α-ketoglutarate and 2-hydroxyglutarate levels without affecting succinate and citrate levels, indicating a partial inhibition of the TCA cycle. This indirect effect is associated with NRF2 (also known as NFE2L2) activation and anti-oxidant responses. These results suggest a moonlighting role of BCAT1 through redox-mediated control of mitochondrial function during early macrophage activation

Acute Iron Deprivation Reprograms Human Macrophage Metabolism and Reduces Inflammation In Vivo.

Iron is an essential metal that fine-tunes the innate immune response by regulating macrophage function, but an integrative view of transcriptional and metabolic responses to iron perturbation in macrophages is lacking. Here, we induced acute iron chelation in primary human macrophages and measured their transcriptional and metabolic responses. Acute iron deprivation causes an anti-proliferative Warburg transcriptome, characterized by an ATF4-dependent signature. Iron-deprived human macrophages show an inhibition of oxidative phosphorylation and a concomitant increase in glycolysis, a large increase in glucose-derived citrate pools associated with lipid droplet accumulation, and modest levels of itaconate production. LPS polarization increases the itaconate:succinate ratio and decreases pro-inflammatory cytokine production. In rats, acute iron deprivation reduces the severity of macrophage-dependent crescentic glomerulonephritis by limiting glomerular cell proliferation and inducing lipid accumulation in the renal cortex. These results suggest that acute iron deprivation has in vivo protective effects mediated by an anti-inflammatory immunometabolic switch in macrophages.This work was supported by the Medical Research Council (MR/M004716/1 and MR/N01121X/1, to J.B., and MRC_MC_UU_12022/6, to C.F.

Prevenció de la infecció respiratòria

Infecció respiratòria; Prevenció; Atenció sanitàriaInfección respiratória; Prevención; Atención sanitáriaRespiratory infection; Prevention; Health careMonografia sobre temes concrets relacionats amb la prevenció de la infecció respiratòria relacionada amb l‟atenció sanitària. Ha estat elaborada per un comitè d‟experts amb una àmplia trajectòria en el camp de l'atenció a pacients amb problemes respiratoris. El document comença fent una posada al dia de l‟epidemiologia i l‟etiopatogènia de les infeccions respiratòries nosocomials i, sense voler repetir capítols de la monografia d'aïllaments, continua fent una pinzellada de les mesures que cal dur a terme per evitar la transmissió de les infeccions respiratòries dins dels centres sanitaris. Tot seguit, s‟aborden de manera pràctica situacions quotidianes, com el maneig de la via aèria, i es fan algunes recomanacions sobre com dur-les a terme. Una part important i poc coneguda per molts professionals és la prevenció de la infecció respiratòria de causa instrumental, motiu pel qual en el darrer capítol es fa una revisió minuciosa de com procedir per reutilitzar aquests aparells.Monografía sobre temas concretos relacionados con la prevención de la infección respiratoria con la atención sanitaria. Ha sido elaborada por un comité de expertos con una amplia trayectoria en el campo de la atención a pacientes con problemas respiratorios. El documento empieza haciendo una puesta al día de la epidemiologia y la etiopatogenia de las infecciones respiratorias nosocomiales y, sin querer repetir capítulos de la monografía de aislamientos, continua haciendo una pincelada de las medidas que son necesarias para evitar la transmisión de las infecciones respiratorias dentro de los centros sanitarios. Seguidamente se tratan de manera práctica situaciones cotidianas, como el manejo de la vía aérea y se hacen algunas recomendaciones sobre como llevarlas a cabo. Una parte importante y poco conocida para muchos profesionales es la prevención de la infección respiratoria de causa instrumental, motivo por el cual en el último capítulo se hace una revisión minuciosa de como proceder para reutilizar estos aparatos

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift, Spain, 2007 to 2019

Altres ajuts: Departament de Salut. Generalitat de Catalunya ("Pla estratègic de recerca i innovació en salut (PERIS) 2019-2021"); Ministerio de Asuntos Económicos y Transformación Digital; Red Española de Investigación en Patología Infecciosa (REIPI).Background: Catheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death. Aim: To analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat). Methods: A cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007-2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000patientdays. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000patientdays and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported. Results: During the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate:0.20episodes/1,000patientdays). Patients' median age was 64.1years; 36.6% (3,403/9,290) were female. In total, 73.7% (n=6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n=5,822) were related to central venous catheter (CVC), 24.1% (n=2,236) to peripheral venous catheters (PVC) and 13.3% (n=1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR:0.94;95%CI:0.93-0.96), especially in the ICU (IRR:0.88;95%CI:0.87-0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR:0.88;95%CI:0.87-0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC:1.08;95%CI:1.05-1.11; IRR PVC: 1.03; 95% 1.00-1.05). Conclusions: Over the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

The role of white adipose tissue oxylipins in obesity

Obesity is characterized by the expansion of the white adipose tissue (WAT), which is associated with the risk of suffering from metabolic diseases including type 2 diabetes mellitus (T2DM). Adequate rates of adipocyte differentiation (adipogenesis) promote healthy WAT expansion and metabolic homeostasis. Healthy WAT expansion buffers lipids, preventing ectopic lipid accumulation in organs such as the muscle and liver. On the other hand, pathological WAT expansion, characterized by adipocyte hypertrophy, hypoxia, inflammation and fibrosis, leads to WAT dysfunction and metabolic decline, including hyperlipidaemia and hyperglycaemia. Oxylipins are bioactive lipid mediators that regulate adipogenesis, but little is known about the specific role of the epoxyganase (CytochromeP450) pathway during adipogenesis. In this thesis, we characterized the major CYP2J epoxygenases and established their contribution to adipogenesis in human and rat adipocyte precursor (AP) cells. We first report that inactivation of CYP2J induces spontaneous adipocyte differentiation. We next sought to understand the consequences of CYP2J depletion and spontaneous adipogenesis in whole-body metabolic homeostasis. We used two obesogenic models (Cafeteria diet and ageing) in rats lacking the main WAT epoxygenase (Cyp2j4). The Cyp2j4-/- rats showed relatively higher rates of adipogenesis at basal conditions, which caused increased adiposity and WAT dysfunction upon obesogenic conditions. WAT dysfunction was characterized by adipocyte hypertrophy, macrophage infiltration, interstitial collagen deposition, and elevated pro-inflammatory oxylipin levels (i.e. prostaglandins). Moreover, Cyp2j4-/- rats showed exacerbated hepatic lipid accumulation and insulin resistance, causing unrestrained hepatic glucose production, a hallmark of T2DM. WAT dysfunctional features, including increased macrophage infiltration and collagen deposition, were conserved in obese patients with T2DM when compared to obese but non-T2DM patients. Prostaglandins were also increased in the WAT of T2DM patients. In humans and rats, the association between macrophage infiltration, collagen deposition and prostaglandin levels suggested macrophages as regulators of WAT collagen deposition, possibly through prostaglandin secretion. Therefore, we proposed an alternative usage of oxylipin precursors towards prostaglandin biosynthesis and metabolism in WAT dysfunction, unveiling prostaglandins as a potential therapeutic target to treat WAT inflammation and fibrosis. Together these results elucidate the role of epoxygenases and prostaglandins in regulating adipocyte differentiation, WAT expansion and inflammation.Open Acces

Perspectiva escolar

En el artículo se analizan las líneas de trabajo abiertos al IES Ronda de LLeida para evitar la insatisfacción que sintieron después de la primera junta de evaluación de etapa. Se defiende la idea de combinar un modelo de evaluación de etapa muy formal con un trabajo rico, comprometido y participativo en todas las áreas curriculares de educación secundaria.CataluñaES

De la tutoria a l'equip docent

Documento incluído dentro del volumen 'Experiències d'innovació educativa. Acció tutorial i formació'. La finalidad del equipo docente es dotar al centro de un instrumento para atender la diversidad de alumnos con un mínimo de garantías de calidad. La tutoría pretende influir sobre el currículum y no sólo sobre el alumno y el entorno familiar, acercándose más a a la realidad y evolución de los alumno. Se cuenta con la participación activa del conjunto de profesores que intervienen en el proceso de enseñanza-aprendizaje. Se presentan los objetivos del proyecto, las tareas para alcanzarlos, los elementos personales y materiales y el proceso y estrategias para el desarrollo de la acción tutorial. Se añade un apartado sobre la evolución de la innovación.Generalitat de Catalunya. Direcció General de Programes i Serveis EducatiusCataluñaES