Biomarkers.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and the leading cause of dementia in the elderly. New approaches to study AD are still needed to identify and validate blood-based diagnostic biomarkers that could be useful for its early diagnosis. Circulating autoantibodies (AAbs) and their target proteins (autoantigens) are promising candidate biomarkers to aid in AD early diagnosis.

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.