Steroids and steroid-like compounds alter the ion permeability of phospholipid bilayers distinct interactions with lipids and interfacial water.

Steroids are organic compounds found in all forms of biological life. Besides their structural roles in cell membranes, steroids act as signalling molecules in various physiological processes and are used to treat inflammatory conditions. It has been hypothesised that in addition to their well-characterised genomic and non-genomic pathways, steroids exert their biological or pharmacological activities an indirect, nonreceptor-mediated membrane mechanism caused by steroid-induced changes to the physicochemical properties of cell membranes.

Effect of digital health applications with or without gamification on physical activity and cardiometabolic risk factors: a systematic review and meta-analysis of randomized controlled trials.

Background: Use of health applications (apps) to support healthy lifestyles has intensified. Different app features may support effectiveness, including gamification defined as the use of game elements in a non-game situation. Whether health apps with gamification can impact behaviour change and cardiometabolic risk factors remains unknown.

Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial.

Background: Psilocybin therapy (PT) produces rapid and persistent antidepressant effects in major depressive disorder (MDD). However, the long-term effects of PT have never been compared with gold-standard treatments for MDD such as pharmacotherapy or psychotherapy alone or in combination.

Methods: This is a 6-month follow-up study of a phase 2, double-blind, randomised, controlled trial involving patients with moderate-to-severe MDD.

HIV interventions across the care continuum for adolescents in high-burden countries: a systematic review and meta-analysis.

Background: Adolescents (10-19 years old) have poor outcomes across the prevention-to-treatment HIV care continuum, leading to significant mortality and morbidity. We conducted a systematic review and meta-analysis of interventions that documented HIV outcomes among adolescents in HIV high-burden countries.

Methods: We searched PubMed, EMBASE, Scopus, and the Cochrane Library for studies published between January 2015 and September 2024, assessing at least one HIV outcome along the prevention-to-care cascade, including PrEP uptake, HIV testing, awareness of HIV infections, ARV adherence, retention, and virological suppression.

Medication non-adherence: reflecting on two decades since WHO adherence report and setting goals for the next twenty years.

Background: Non-adherence to medication remains a persistent and significant challenge, with profound implications for patient outcomes and the long-term sustainability of healthcare systems. Two decades ago, the World Health Organization (WHO) dedicated its seminal report to adherence to long-term therapies, catalysing notable changes that advanced both research and practice in medication adherence. The aim of this paper was to identify the most important progress made over the last 2 decades in medication adherence management and to initiate a discussion on future objectives, suggesting priority targets for the next 20 years.

Connection between -electron correlations and magnetic excitations in UTe.

The detailed anisotropic dispersion of the low-temperature, low-energy magnetic excitations of the candidate spin-triplet superconductor UTe is revealed using inelastic neutron scattering. The magnetic excitations emerge from the Brillouin zone boundary at the high symmetry and points and disperse along the crystallographic -axis. In applied magnetic fields to at least = 11 T along the , the magnetism is found to be field-independent in the ( 0) plane.

Evidence of multiple bacterial, viral, and parasitic infectious disease agents in rodents in riverine areas in selected parts of Zambia.

Background: Infectious disease agents pose significant threats to humans, wildlife, and livestock, with rodents carrying a third of these agents, many linked to human diseases. However, the range of pathogens in rodents and the hotspots for disease remain poorly understood.

Aim: This study evaluated the prevalence of viral, bacterial, and parasitic pathogens in rodents in riverine and non-riverine areas in selected districts in Zambia.

Benchmarking lung cancer screening programmes with adaptive screening frequency against the optimal screening schedules derived from the ENGAGE framework: a comparative microsimulation study.

Background: Lung cancer screening recommendations employ annual frequency for eligible individuals, despite evidence that it may not be universally optimal. The impact of imposing a structure on the screening frequency remains unknown. The ENGAGE framework, a validated framework that offers fully dynamic, analytically optimal, personalised lung cancer screening recommendations, could be used to assess the impact of screening structure on the effectiveness and efficiency of lung cancer screening.

Mechanistic insights into endosomal escape by sodium oleate-modified liposomes.

Endosomal entrapment significantly limits the efficacy of drug delivery systems. This study investigates sodium oleate-modified liposomes (SO-Lipo) as an innovative strategy to enhance endosomal escape and improve cytosolic delivery in 4T1 triple-negative breast cancer cells. We aimed to elucidate the mechanistic role of sodium oleate in promoting endosomal escape and compared the performance of SO-Lipo with unmodified liposomes (Unmodified-Lipo) and Aurein 1.

In silico discovery of potential inhibitors targeting the MEIG1-PACRG complex for male contraceptive development.

The interaction between meiosis-expressed gene 1 (MEIG1) and Parkin co-regulated gene (PACRG) is a critical determinant of spermiogenesis, the process by which round spermatids mature into functional spermatozoa. Disruption of the MEIG1-PACRG complex can impair sperm development, highlighting its potential as a therapeutic target for addressing male infertility or for the development of non-hormonal contraceptive methods. This study used virtual screening, molecular docking, and molecular dynamics (MD) simulations to identify small molecule inhibitors targeting the MEIG1-PACRG interface.

The PH domain in the ArfGAP ASAP1 drives catalytic activation through an unprecedented allosteric mechanism.

ASAP1 is a multidomain Arf GTPase-activating protein (ArfGAP) that catalyzes GTP hydrolysis on the small GTPase Arf1 and is implicated in cancer progression. The PH domain of ASAP1 enhances its activity greater than 7 orders of magnitude but the underlying mechanisms remain poorly understood. Here, we combined Nuclear Magnetic Resonance (NMR), Molecular Dynamic (MD) simulations and mathematical modeling of functional data to build a comprehensive structural-mechanistic model of the complex of Arf1 and the ASAP1 PH domain on a membrane surface.

Enhanced identification of small molecules binding to hnRNPA1 via cryptic pockets mapping coupled with X-Ray fragment screening.

The human heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a prototypical RNA-binding protein essential in regulating a wide range of post-transcriptional events in cells. As a multifunctional protein with a key role in RNA metabolism, deregulation of its functions has been linked to neurodegenerative diseases, tumour aggressiveness and chemoresistance, which has fuelled efforts to develop novel therapeutics that modulates its RNA binding activities. Here, using a combination of Molecular Dynamics (MD) simulations and graph neural network pockets predictions, we showed that hnRNPA1 N-terminal RNA binding domain (UP1) contains several cryptic pockets capable of binding small molecules.

Predicting protein curvature sensing across membrane compositions with a bilayer continuum model.

Unlabelled: Cytoplasmic proteins must recruit to membranes to function in processes such as endocytosis and cell division. Many of these proteins recognize not only the chemical structure of the membrane lipids, but the curvature of the surface, binding more strongly to more highly curved surfaces, or 'curvature sensing'. Curvature sensing by amphipathic helices is known to vary with membrane bending rigidity, but changes to lipid composition can simultaneously alter membrane thickness, spontaneous curvature, and leaflet symmetry, thus far preventing a systematic characterization of lipid composition on such curvature sensing through either experiment or simulation.

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.

Geny: a genotyping tool for allelic decomposition of killer cell immunoglobulin-like receptor genes.

Introduction: Accurate genotyping of Killer cell Immunoglobulin-like Receptor (KIR) genes plays a pivotal role in enhancing our understanding of innate immune responses, disease correlations, and the advancement of personalized medicine. However, due to the high variability of the KIR region and high level of sequence similarity among different KIR genes, the generic genotyping workflows are unable to accurately infer copy numbers and complete genotypes of individual KIR genes from next-generation sequencing data. Thus, specialized genotyping tools are needed to genotype this complex region.

Critical Care Management of Acute Venous Thromboembolism: Integrating Pharmacotherapy, Thrombectomy, and Temporary Mechanical Support.

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, carries significant morbidity and mortality risks, and is conventionally managed with anticoagulation. In recent years, notable progress has been made in the therapeutic options available for the acute treatment of VTE. The heterogeneity within pulmonary embolism, spanning a wide spectrum of risks, underscores the critical need for precise risk stratification, particularly in identifying individuals prone to right heart failure and increased mortality.

Long-term prescription opioid use following surgery in the US (2017-2022): a population-based study.

Background: Over the last decade, numerous efforts have been made to combat the opioid crisis globally. The impact of these strategies has not been adequately measured and may differ across populations depending on baseline risk. We compared changes in long-term prescription opioid use following surgery within a national US cohort, between 2017 and 2022.

Climate change, migration, and health: perspectives from Latin America and the Caribbean.

This article delves into the complex relationship between climate change, migration patterns, and health outcomes in Latin America and the Caribbean (LAC). While the severe impact of climate change on health in LAC is widely acknowledged, the article sheds light on the often-overlooked multiple effects on migration and the well-being of migrants. These impacts encompass poverty, food and water insecurity, and adverse physical and mental health outcomes.

The response of health systems to the needs of migrants and refugees in the COVID-19 pandemic: a comparative case study between Mexico, Colombia and Peru.

Background: Protecting the health of migrants and refugees during the pandemic was a significant challenge in the Latin American region. We aimed to describe and contrast the response of the health systems of Mexico, Colombia and Perú to migrants' and refugees' health needs during the COVID-19 pandemic, and to situate the response in the context of the migration and health policies of each country.

Methods: We conducted case studies of the three countries.

Incisor cross-sectional area at the cementoenamel junction correlates with an increased reliance on frugivory in anthropoid primates.

Diet is one of a limited set of key ecological parameters defining primate species. A detailed understanding of dental functional correlates with primate diet is a key component for accurate dietary inference in fossil primates. Although considerable effort has been devoted to understanding post-canine dental function, incisor function remains poorly understood.

Glutamine metabolism is systemically different between primary and induced pluripotent stem cell-derived brain microvascular endothelial cells.

Human primary (hpBMEC) and induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial-like cells (hiBMEC) are interchangeably used in blood-brain barrier models to study neurological diseases and drug delivery. Both hpBMEC and hiBMEC use glutamine as a source of carbon and nitrogen to produce metabolites and build proteins essential to cell function and communication. We used metabolomic, transcriptomic, and computational methods to examine how hpBMEC and hiBMEC metabolize glutamine, which may impact their utility in modeling the blood-brain barrier.

The safety and efficacy of anti-inflammatory-impregnated gelatin sponge in spine surgery: a systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis is to evaluate the safety and efficacy of anti-inflammatory-impregnated gelatin sponges in spine surgeries. Gelatin sponges are increasingly used as delivery vehicles for anti-inflammatory and analgesic drugs during spine surgeries. However, concerns about their safety and efficacy persist.

Identifying and Understanding Seizure Liability in Drug Development.

Seizures are complex electrophysiological disturbances affecting one or more populations of brain neurons. Seizures following test article (TA) exposure pose significant challenges in drug development. This paper considers the diverse neurological manifestations, mechanisms, and functional and structural assessments needed to investigate TA-related seizure liabilities, with a particular focus on nonclinical species.

The relative cerebral blood volume (rCBV) < 42% is independently associated with hemorrhagic transformation in anterior circulation large vessel occlusion.

Background: Pretreatment CT perfusion (CTP) marker relative cerebral blood volume (rCBV) < 42% lesion volume has recently shown to predict poor collateral status and poor 90-day functional outcome. However, there is a paucity of studies assessing its association with hemorrhagic transformation (HT). Here, we aim to assess the relationship between rCBV < 42% lesion volume with HT.