Dyssynchrony and the risk of ventricular arrhythmias

OBJECTIVES: The aim of our study was to evaluate the relationship between left ventricular (LV) dyssynchrony and the risk of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) trial. BACKGROUND: Intraventricular mechanical dyssynchrony might be an important factor in ventricular arrhythmogenesis by enhancing electrical heterogeneity in heart failure patients. The effects of dyssynchrony have not yet been evaluated in a large cohort of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy with defibrillator (CRT-D) patients. METHODS: LV dyssynchrony was measured at baseline and at 12-months by speckle-tracking echocardiography, defined as the standard deviation of time to peak systolic strain in 12 LV myocardial segments. The endpoint was the first VT/VF/death or VT/VF. LV dyssynchrony was evaluated in 764 left bundle branch block (LBBB) patients and in 312 non-LBBB patients. RESULTS: Baseline LV dyssynchrony was not predictive of VT/VF/death or VT/VF in LBBB or non-LBBB patients in either treatment arm. In CRT-D patients with LBBB, improvement in LV dyssynchrony over a year was associated with significantly lower incidence of VT/VF/death (p < 0.001) and VT/VF (p < 0.001) compared to ICD patients and to CRT-D patients with unchanged or worsening dyssynchrony. Among LBBB patients, 15% decrease in LV dyssynchrony was associated with lower risk of VT/VF/death (hazard ratio: 0.49, 95% confidence interval: 0.24 to 0.99, p = 0.049) and VT/VF (hazard ratio: 0.30, 95% confidence interval: 0.12 to 0.77, p = 0.009) as compared to ICD patients. Patients without LBBB receiving CRT-D did not show reduction in VT/VF/death or in VT/VF in relation to improving dyssynchrony when evaluating cumulative event rates or risk of events. CONCLUSIONS: Baseline LV dyssynchrony did not predict VT/VF/death or VT/VF in mild heart failure patients with or without LBBB. CRT-induced improvement of LV dyssynchrony was associated with significant reduction of ventricular arrhythmias in patients with LBBB. (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271)

Innate immunity defines the capacity of antiviral T cells to limit persistent infection

Effective immunity requires the coordinated activation of innate and adaptive immune responses. Natural killer (NK) cells are central innate immune effectors, but can also affect the generation of acquired immune responses to viruses and malignancies. How NK cells influence the efficacy of adaptive immunity, however, is poorly understood. Here, we show that NK cells negatively regulate the duration and effectiveness of virus-specific CD4+ and CD8+ T cell responses by limiting exposure of T cells to infected antigen-presenting cells. This impacts the quality of T cell responses and the ability to limit viral persistence. Our studies provide unexpected insights into novel interplays between innate and adaptive immune effectors, and define the critical requirements for efficient control of viral persistence

Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins

Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer's disease (AD), Huntingtin (HTT) for Huntington's disease, Parkin (PARK2) for Parkinson's disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.Peer reviewe

Envejecimiento de la población

&bull;Actividades b&aacute;sicas de la vida diaria en personas mayores y factores asociados &bull;Asociaci&oacute;n entre depresi&oacute;n y posesi&oacute;n de mascotas en personas mayores &bull;Calidad de vida en adultos mayores de Santiago aplicando el instrumento WHOQOL-BREF &bull;Calidad de vida en usuarios con enfermedad de Parkinson, demencia y sus cuidadores, comuna de Vitacura &bull;Caracterizaci&oacute;n de egresos hospitalarios de adultos mayores en Puerto Natales (2007-2009) &bull;Comportamiento de las patolog&iacute;as incluidas como GES para el adulto mayor atendido en un Cesfam &bull;Contribuci&oacute;n de vitaminas y minerales a las ingestas recomendadas diarias en ancianos institucionalizados de Madrid &bull;Estado de salud oral del paciente inscrito en el Programa de Visita Domiciliaria &bull;Evaluaci&oacute;n del programa de discapacidad severa en Casablanca con la matriz de marco l&oacute;gico &bull;Factores asociados a satisfacci&oacute;n vital en una cohorte de adultos mayores de Santiago, Chile &bull;Pauta instrumental para la identificaci&oacute;n de riesgos para el adulto mayor autovalente, en su vivienda &bull;Perfil farmacol&oacute;gico del paciente geri&aacute;trico institucionalizado y posibles consecuencias en el deterioro cognitivo &bull;Programa de cuidados paliativos y alivio del dolor en Puerto Natales &bull;Rehabilitaci&oacute;n mandibular implantoprot&eacute;sica: efecto en calidad de vida relacionada con salud bucal en adultos mayores &bull;Salud bucodental en adultos mayores autovalentes de la Regi&oacute;n de Valpara&iacute;so &bull;Transici&oacute;n epidemiol&oacute;gica y el estudio de carga de enfermedad en Brasi

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe