Hypothalamic SIRT1-mediated regulation of the hormonal trigger of ovulation and its repression in energy deficit.

Female reproduction is highly sensitive to body energy stores; persistent energy deficit, as seen in anorexia or strenuous exercise, is known to suppress ovulation via ill-defined mechanisms. We report herein that hypothalamic SIRT1, a key component of the epigenetic machinery that links nutritional status and puberty onset via modulation of Kiss1, plays a critical role in the control of the preovulatory surge of gonadotropins, i.e.

Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators.

In silico trials for drug safety assessment require many high-fidelity 3D cardiac simulations to predict drug-induced QT interval prolongation, which is often computationally prohibitive. To streamline this process, we developed sex-specific emulators for a fast prediction of QT interval, trained on a dataset of 900 simulations. Our results show significant differences between 3D and 0D single-cell models as risk levels increase, underscoring the ability of 3D modeling to capture more complex cardiac responses.

Optimization of Clozapine Treatment: Study of Variables Affecting Response in Uruguayan Patients With Schizophrenia.

Purpose/background: Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia.

Clinical phenotypes in acute and chronic infarction explained through human ventricular electromechanical modelling and simulations.

Sudden death after myocardial infarction (MI) is associated with electrophysiological heterogeneities and ionic current remodelling. Low ejection fraction (EF) is used in risk stratification, but its mechanistic links with pro-arrhythmic heterogeneities are unknown. We aim to provide mechanistic explanations of clinical phenotypes in acute and chronic MI, from ionic current remodelling to ECG and EF, using human electromechanical modelling and simulation to augment experimental and clinical investigations.

Effects of alcohol-related problems on the costs of frequent emergency department use: an economic analysis of a case-control study in Spain.

Introduction: Alcohol-related problems increase the probability of frequent emergency department (ED) use. In this study, we compared the direct healthcare expenses incurred during a single visit among frequent and non-frequent ED users and analyzed the impact of alcohol-related issues in healthcare costs arising from ED usage.

Methods: The study relied on secondary analyses of economic data from a 1:1 matched case-control study with the primary aim of identifying the clinical characteristics of hospital ED frequent users in a Mediterranean European environment with a public, universal, and tax-funded health system.