Remodelado estructural y de GAP Junctions en un modelo 3D de aurícula humana

Introducción:la fibrilación auricular (AF), es la más común de la arritmia cardiaca sostenida y un factor de riesgo para el accidente cerebro vascular y otras morbilidades, si no es tratada. Estudios epidemiológicos muestran que la AF tiende a perpetuarse con el tiempo, generando cambios electrofisiológicos y anatómicos denominados: remodelados auriculares. Se ha demostrado que estos cambios provocan variaciones de la velocidad de conducción (CV), en el tejido auricular. Objetivo:estudiar el efecto del remodelado de gap junctions en la propagación del potencial de acción, implementando un modelo 3D de aurícula humana altamente realista. Materiales y Métodos:se incorporaron los cambios generados por el remodelado eléctrico a un modelo de potencial de acción (AP) de miocito auricular, acoplado con un modelo tridimensional anatómicamente realista de aurícula humana dilatada. Mediante simulaciones de la propagación del AP en condiciones de remodelado eléctrico y anatómico, y de remodelado de gap junctions, se midieron las ventanas vulnerables de generación de reentradas en la base de las venas pulmonares izquierdas de la aurícula. Resultados:los resultados obtenidos indican que la ventana vulnerable en el remodelado de gap junctions, se desplazó 38 ms con relación al modelo dilatado, lo que nos muestra el impacto de la dilatación con remodelado de gap junction. Conclusiones:el remodelado eléctrico generó una disminución del 70 % en la duración del potencial de acción y una disminución de las velocidades de conducción entre un 14.6 y un 26 %, que fueron medidas en diferentes regiones de la aurícula dilatada. El foco disparado en la base de las venas pulmonares izquierdas, generó un frente de onda que mantiene una actividad reentrante debido a la anatomía subyacente de las venas pulmonares.Introduction:Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a significant risk factor for cerebrovascular accident and other morbidities if left untreated. Epidemiological studies show that AF tends to persist over time, creating electrophysiological and anatomical changes called atrial remodeling. It has been shown that these changes result in variations in conduction velocity (CV) in the atrial tissue. Objective:to study the effect of remodeling of gap junctions in the propagation of the action potential by implementing a highly realistic 3D human atrial model. Materials and methods:the changes caused by electrical remodeling were incorporated in an atrial myocyte action potential (AP) model coupled with an anatomically realistic three-dimensional model of dilated human atria. Through simulations of the AP spread in variations of anatomical and electrical remodeling and of gap junctions remodeling, vulnerable windows of reentry generation were measured at the base of the atrium left pulmonary veins. Results:the results obtained indicate that vulnerable window in the gap junctions remodeling moved 38 ms in relation with the expanded model which shows the impact of the dilatation gap junction remodeling. Conclusions:the electrical remodeling produced 70% decrease in action potential duration and decreased conduction velocities between 14.6 and 26 %, which were measured in different regions of the dilated atrium. The focus shot at the base of the left pulmonary veins created a wave which maintains a reentering activity due to the underlying anatomy of the pulmonary veins

Efecto de la frecuencia del ritmo sinusal en la generación de reentradas en un modelo 3D de aurícula humana remodelada

Las arritmias auriculares son las taquiarritmias más comunes en humanos. Recientemente, se ha demostrado que una actividad ectópica alrededor de las venas pulmonares puede generar mecanismos reentrantes en presencia de un sustrato vulnerable. En este estudio, examinamos el efecto de la frecuencia del ritmo sinusal para contribuir en la generación de mecanismos reentrantes iniciados por actividad ectópica. Los efectos del remodelado en las corrientes iónicas se incorporaron en un modelo 3D de aurícula humana, altamente realista. Sólo a altas frecuencias del ritmo sinusal (longitud del ciclo base ≤ 300 ms), la actividad ectópica provocó la generación de reentradas en figura de ocho en la aurícula derecha. Nuestro estudio sugiere que la interacción de actividad ectópica con un ritmo sinusal a alta frecuencia facilita la generación de mecanismos reentrantes en aurícula humana remodelada

Evaluación de la remoción de arsénico en agua superficial utilizando filtros domiciliarios

El objetivo del estudio fue evaluar filtros domiciliarios para remover arsénico presente en agua proveniente del río Sama. El sistema estuvo compuesto de un filtro tradicional de arena y un filtro con el material adsorbente de hierro cerovalente estabilizado en quitosano. La evaluación del sistema fue por un período de 12 semanas en 18 puntos de uso; las primeras ocho semanas se determinó la concentración de arsénico del agua filtrada empleando tiras reactivas, y las cuatro últimas fueron a través de espectrometría de absorción atómica (EAA-FIAS). Durante las primeras ocho semanas se redujo la concentración de arsénico en el rango de 0,005 y 0,025 mg/L, y durante las cuatro últimas en el rango de 0,001 y 0,052 mg/L, a partir de una concentración promedio de 0,51 mg/L. Se demostró que el sistema de filtración es eficiente para remover arsénico a condiciones naturales

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Search for supersymmetry at √s=13 TeV in final states with jets and two same-sign leptons or three leptons with the ATLAS detector

A search for strongly produced supersymmetric particles is conducted using signatures involving multiple energetic jets and either two isolated leptons (e or μ μ) with the same electric charge or at least three isolated leptons. The search also utilises b-tagged jets, missing transverse momentum and other observables to extend its sensitivity. The analysis uses a data sample of proton–proton collisions at √s=13 TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015 corresponding to a total integrated luminosity of 3.2 fb −1. No significant excess over the Standard Model expectation is observed. The results are interpreted in several simplified supersymmetric models and extend the exclusion limits from previous searches. In the context of exclusive production and simplified decay modes, gluino masses are excluded at 95% 95% confidence level up to 1.1–1.3 TeV for light neutralinos (depending on the decay channel), and bottom squark masses are also excluded up to 540 GeV. In the former scenarios, neutralino masses are also excluded up to 550–850 GeV for gluino masses around 1 TeV

Search for supersymmetry in events with large missing transverse momentum, jets, and at least one tau lepton in 20 fb−1 of √s=8 TeV proton-proton collision data with the ATLAS detector

A search for supersymmetry (SUSY) in events with large missing transverse momentum, jets, at least one hadronically decaying tau lepton and zero or one additional light leptons (electron/muon), has been performed using 20.3fb−1 of proton-proton collision data at √s= 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. No excess above the Standard Model background expectation is observed in the various signal regions and 95% confidence level upper limits on the visible cross section for new phenomena are set. The results of the analysis are interpreted in several SUSY scenarios, significantly extending previous limits obtained in the same final states. In the framework of minimal gauge-mediated SUSY breaking models, values of the SUSY breaking scale Λ below 63 TeV are excluded, independently of tan β. Exclusion limits are also derived for an mSUGRA/CMSSM model, in both the R-parity-conserving and R-parity-violating case. A further interpretation is presented in a framework of natural gauge mediation, in which the gluino is assumed to be the only light coloured sparticle and gluino masses below 1090 GeV are excluded

Search for direct top-squark pair production in final states with two leptons in pp collisions at √s = 8TeV with the ATLAS detector

A search is presented for direct top-squark pair production in final states with two leptons (electrons or muons) of opposite charge using 20.3 fb−1 of pp collision data at √s = 8 TeV, collected by the ATLAS experiment at the Large Hadron Collider in 2012. No excess over the Standard Model expectation is found. The results are interpreted under the separate assumptions (i) that the top squark decays to a b-quark in addition to an on-shell chargino whose decay occurs via a real or virtual W boson, or (ii) that the top squark decays to a t-quark and the lightest neutralino. A top squark with a mass between 150 GeV and 445 GeV decaying to a b-quark and an on-shell chargino is excluded at 95% confidence level for a top squark mass equal to the chargino mass plus 10 GeV, in the case of a 1 GeV lightest neutralino. Top squarks with masses between 215 (90) GeV and 530 (170) GeV decaying to an on-shell (off-shell) t-quark and a neutralino are excluded at 95% confidence level for a 1 GeV neutralino

Search for top squark pair production in final states with one isolated lepton, jets, and missing transverse momentum in √s = 8 TeV pp collisions with the ATLAS detector

The results of a search for top squark (stop) pair production in final states with one isolated lepton, jets, and missing transverse momentum are reported. The analysis is performed with proton-proton collision data at s√ = 8 TeV collected with the ATLAS detector at the LHC in 2012 corresponding to an integrated luminosity of 20 fb−1. The lightest supersymmetric particle (LSP) is taken to be the lightest neutralino which only interacts weakly and is assumed to be stable. The stop decay modes considered are those to a top quark and the LSP as well as to a bottom quark and the lightest chargino, where the chargino decays to the LSP by emitting a W boson. A wide range of scenarios with different mass splittings between the stop, the lightest neutralino and the lightest chargino are considered, including cases where the W bosons or the top quarks are off-shell. Decay modes involving the heavier charginos and neutralinos are addressed using a set of phenomenological models of supersymmetry. No significant excess over the Standard Model prediction is observed. A stop with a mass between 210 and 640 GeV decaying directly to a top quark and a massless LSP is excluded at 95% confidence level, and in models where the mass of the lightest chargino is twice that of the LSP, stops are excluded at 95% confidence level up to a mass of 500 GeV for an LSP mass in the range of 100 to 150 GeV. Stringent exclusion limits are also derived for all other stop decay modes considered, and model-independent upper limits are set on the visible cross-section for processes beyond the Standard Model