Small Molecule Modulators of β-arrestins.

Unlabelled: β-arrestins (βarrs) are key regulators of G protein-coupled receptors (GPCRs), essential for modulating signaling pathways and physiological processes. While current pharmacological strategies target GPCR orthosteric and allosteric sites, as well as G protein transducers, comparable tools for studying βarrs are lacking. Here, we present the discovery and characterization of novel small-molecule allosteric inhibitors of βarrs through comprehensive biophysical, biochemical, pharmacological, and structural analyses.

A Novel Homozygous Loss-of-Function Variant in GPR156 Delineates Non-syndromic Hearing Loss.

Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder accounting for almost 70% of the total congenital hearing loss. The implementation of rapid advanced sequencing methods has significantly contributed to the correct molecular diagnosis for several rare genetic disorders, including NHSL. Features of two probands with NHSL were clinically and genetically evaluated.

Preparing Physicians of the Future: Incorporating Data Science into Medical Education.

The recent excitement surrounding artificial intelligence (AI) in health care underscores the importance of physician engagement with new technologies. Future clinicians must develop a strong understanding of data science (DS) to further enhance patient care. However, DS remains largely absent from medical school curricula, even though it is recognized as vital by medical students and residents alike.

Pituitary adenylate cyclase-activating polypeptide (PACAP)overexpression in the paraventricular nucleus of the thalamus alters motivated and affective behavior in female rats.

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) has been found to be involved in a wide range of motivated and affective behaviors. While the PACAP-38 isoform is more densely expressed than PACAP-27 in most of the brain, PACAP-27 is more highly expressed in the rodent paraventricular nucleus of the thalamus (PVT), where females also have greater expression than males. Notably, the role of PACAP-27 expression in cells of the PVT has not been explored.

Comparing outcomes of Aquablation versus holmium laser enucleation of prostate in the treatment of benign prostatic hyperplasia: A network meta-analysis.

Introduction: Water Jet Ablation Therapy (WJAT) and Holmium Laser Enucleation of the Prostate (HoLEP) represent two common surgical treatments for Benign Prostatic Hyperplasia (BPH). Despite their increasing use, there is no study between these two methods. We aim to evaluate their efficacy and safety through a network meta-analysis (NMA), providing critical insights for clinical decision-making in the management of moderate to severe lower urinary tract symptoms (LUTS) due to BPH.