Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain-of-activity mouse model presents with a pre-mature aging-like phenotype and with decreased lifespan. These data suggest a causal connection between elevated activity of Cdc42, aging and reduced lifespan. Here, we demonstrate that systemic treatment of aged (75-week old) female C57BL/6 mice with a Cdc42 activity specific inhibitor (CASIN)...

We recently provided evidence that an intrinsic reward-related signal-triggered by successful learning in absence of any external feedback-modulated the entrance of new information into long-term memory via the activation of the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop; Ripollés et al., 2016). Here, we used a double-blind, within-subject randomized pharmacological intervention to test whether this learning process is indeed dopamine-dependent. A group of healthy individuals completed three behavioral sessions of a language-learning task...

Objective. To assess the utility of QuantiFERON®-TB Gold In-tube (QFT-GIT) for targeting preventive therapy in BCG-vaccinated contacts of tuberculosis (TB), based on its high specificity and negative predictive value for development of TB. Methods. We compared two screening strategies for TB contact tracing in two consecutive periods: the tuberculin skin test (TST) period, when all contacts were screened with the TST alone; and the QFT-GIT period, when BCG-vaccinated contacts underwent TST and QFT-GIT. Diagnosis of...

During X chromosome inactivation (XCI), the inactive X chromosome (Xi) is recruited to the nuclear lamina at the periphery of the nucleus. Beside X chromosome reactivation resulting in a highly penetrant aging-like hematopoietic malignancy, little is known about XCI in aged hematopoietic stem cells (HSCs) . Here, we demonstrate that LaminA/C defines a distinct repressive nuclear compartment for XCI in young HSCs, and its reduction in aged HSCs correlates with an impairment in the overall...

Abstract Background Hemodialysis (HD) patients with atrial fibrillation (AF) have a particularly high risk of stroke and bleeding, but no high-quality evidence-based recommendations exist to properly manage these patients. Objectives We aim to evaluate the ischemic versus the hemorrhagic risk in a HD population with AF. Methods We selected incident patients that started hemodialysis between 2011 and 2015. All patients that had AF before HD, or developed AF during the follow-up, were included. Both CHA2DS2...

Introduction. The role of Pulmonary and Activation-Regulated Chemokine (PARC) in the physiopathology of Chronic Obstructive Pulmonary Disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC in lung tissue and its relationship with the vascular remodeling of the systemic and pulmonary arteries of COPD subjects. Methods. To achieve this objective, protein and gene expression experiments, together with ELISA assays, were performed on the lung tissue, intercostal...

Type 2 diabetes (T2D) is a global public health challenge. Whilst the advent of genome-wide association studies has identified >400 genetic variants associated with T2D, our understanding of its biological mechanisms and translational insights is still limited. The EPIC-InterAct project, centred in 8 countries in the European Prospective Investigations into Cancer and Nutrition study, is one of the largest prospective studies of T2D. Established as a nested case-cohort study to investigate the interplay between genetic...

Background: In Spain, women invited to breast screening are not usually informed about potential harms of screening. The objective of the InforMa study is to assess the effect of receiving information about the benefits and harms of breast screening on informed choice and other decision making outcomes, in women approaching the age of invitation to mammography screening. Methods: Two-stage randomised controlled trial. In the first stage, 40 elementary territorial units of the public healthcare system...

Abstract Background Hemodialysis (HD) patients with atrial fibrillation (AF) have a particularly high risk of stroke and bleeding, but no high-quality evidence-based recommendations exist to properly manage these patients. Objectives We aim to evaluate the ischemic versus the hemorrhagic risk in a HD population with AF. Methods We selected incident patients that started hemodialysis between 2011 and 2015. All patients that had AF before HD, or developed AF during the follow-up, were included. Both CHA2DS2...