Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.

Background And Aims: Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.

Methods: Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring.

Results: Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions.

Insights into the flexibility of the domain-linking loop in actinobacterial coproheme decarboxylase through structures and molecular dynamics simulations.

Prokaryotic heme biosynthesis in Gram-positive bacteria follows the coproporphyrin-dependent heme biosynthesis pathway. The last step in this pathway is catalyzed by the enzyme coproheme decarboxylase, which oxidatively transforms two propionate groups into vinyl groups yielding heme b. The catalytic reaction cycle of coproheme decarboxylases exhibits four different states: the apo-form, the substrate (coproheme)-bound form, a transient three-propionate intermediate form (monovinyl, monopropionate deuteroheme; MMD), and the product (heme b)-bound form.

A novel method for expressing and purifying large quantities of functional and stable human voltage-gated proton channel (hH1).

Purifying membrane proteins has been the limiting step for studying their structure and function. The challenges of the process include the low expression levels in heterologous systems and the requirement for their biochemical stabilization in solution. The human voltage-gated proton channel (hH1) is a good example of that: the published protocols to express and purify hH1 produce low protein quantities at high costs, which is an issue for systematically characterizing its structure and function.

Adjusting for Ascertainment Bias in Meta-Analysis of Penetrance for Cancer Risk.

Multi-gene panel testing allows efficient detection of pathogenic variants in cancer susceptibility genes including moderate-risk genes such as ATM and PALB2. A growing number of studies examine the risk of breast cancer (BC) conferred by pathogenic variants of these genes. A meta-analysis combining the reported risk estimates can provide an overall estimate of age-specific risk of developing BC, that is, penetrance for a gene.

CaML: Chemistry-informed machine learning explains mutual changes between protein conformations and calcium ions in calcium-binding proteins using structural and topological features.

Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes.

Abuse potential and analgesic efficacy of intravenous hydromorphone bolus administration among hospitalized patients with cancer pain: A double-blind, double dummy, randomized crossover trial.

Background: There is much concern that opioids administered as intravenous (iv) bolus for pain relief may inadvertently increase their risk for abuse. However, there is insufficient data to support this. The authors compared the abuse liability potential, analgesic efficacy, and adverse effect profile of fast (iv push) versus slow (iv piggyback) administration of iv hydromorphone among hospitalized patients requiring iv opioids for pain.

Cryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.

Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.

Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis.

Background: The optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.

Methods: A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases.

Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics.

An essential task in spatial transcriptomics is identifying spatially variable genes (SVGs). Here, we present Celina, a statistical method for systematically detecting cell type-specific SVGs (ct-SVGs)-a subset of SVGs exhibiting distinct spatial expression patterns within specific cell types. Celina utilizes a spatially varying coefficient model to accurately capture each gene's spatial expression pattern in relation to the distribution of cell types across tissue locations, ensuring effective type I error control and high power.

Phase I trial of hydroxychloroquine to enhance palbociclib and letrozole efficacy in ER+/HER2- breast cancer.

Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2-negative metastatic breast cancer (ER+/HER2- MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. The autophagy inhibitor hydroxychloroquine (HCQ) induced on-target senescence at lower palbociclib doses.

Gender differences in cognitive impairment among the elderly in rural West Texas counties.

Background: The prevalence of Alzheimer's disease or dementia in the elderly population has been increasing both nationally and globally. Males and females are impacted differently when it comes to cognitive health, and this can be influenced by various risk factors.

Objective: This study highlights the sociodemographic, chronic disease, and genetic biomarker risk factors associated with gender differences and cognitive impairments in the elderly population living in Cochran, Parmer, and Bailey counties of rural West Texas.

Subendocardial ischemia: does CMD really exist?

Patients with angina but without obstructive epicardial coronary disease still require a specific mechanistic diagnosis to enable targeted treatment. The overarching term "coronary microvascular dysfunction" (CMD) has been applied broadly - but is it correct? We present a series of case examples culminating a systematic exploration of our large clinical database to distinguish among four categories of coronary pathophysiology. First, by far the largest group of "no stenosis angina" patients exhibits subendocardial ischemia during intact flow through diffuse epicardial disease during dipyridamole vasodilator stress.

Sex-specific effects on the heart from combined exposure to simulated galactic cosmic radiation and hindlimb unloading.

Future long duration space missions will expose astronauts to higher doses of galactic cosmic radiation (GCR) than those experienced on the international space station. Recent studies have demonstrated astronauts may be at risk for cardiovascular complications due to increased radiation exposure and fluid shift from microgravity. However, there is a lack of direct evidence on how the cardiovascular system is affected by GCR and microgravity since no astronauts have been exposed to exploratory mission relevant GCR doses.

Galactic cosmic ray environment predictions for the NASA BioSentinel Mission, part 2:Post-mission validation.

The BioSentinel CubeSat was deployed on the Artemis-I mission in November 2022 and has been continuously transmitting physical measurements of the space radiation environment since that time. Just before mission launch, we published computational model predictions of the galactic cosmic ray exposure expected inside BioSentinel for multiple locations and configurations. The predictions utilized models for the ambient galactic cosmic ray environment, radiation physics and transport, and BioSentinel geometry.

The hypercapnic environment on the International Space Station (ISS): A potential contributing factor to ocular surface symptoms in astronauts.

With increasing advancements and efforts towards space exploration, there is a pressing need to understand the impacts of spaceflight on astronauts' health. Astronauts have reported signs and symptoms of dry eye disease upon traveling to the International Space Station (ISS), thus necessitating an evaluation of the factors that contribute to the onset of spaceflight associated dry eye disease. Prior literature describes the hypercapnic environment of the ISS; however, the link between the high CO levels and astronauts' symptoms of dry eye disease remains unexplored.

The lived experiences of nurse practitioners during a nursing strike.

Objective: This study aims to understand the lived experiences of nurse practitioners (NPs) providing patient care during a nursing strike in a hospital setting.

Background: The nursing shortage afflicts the provision of health care. A recurring loss of seasoned nurses represents a loss of expertise and organizational knowledge, leading to internal burnout, inadequate resources, and recently, nursing strikes.

Obsessive-compulsive symptoms in individuals with a history of eating disorders.

Background: OCD symptoms are well documented in anorexia nervosa (AN) and to a lesser extent in bulimia nervosa (BN), yet remain virtually unstudied in binge-eating disorder (BED).

Methods: In this cross-sectional observational study, 5927 participants with lifetime eating disorders (EDs) (i.e.

Patient Characteristics, Management and Long-term Outcomes of Patients with Cardiogenic Shock at a Large Safety Net Hospital.

Data regarding cardiogenic shock (CS) from safety-net hospitals serving socioeconomically-disadvantaged patients are limited. In addition, little is known regarding long-term outcomes and management of heart failure-related CS (HF-CS), a population potentially especially vulnerable to adverse social determinants of health (SDOH). A single-center retrospective cohort study of patients with Stage C, D, or E CS at a public safety-net hospital between 2017-2023 was performed.

Diffusion-weighted arterial spin labeling MRI to investigate mannitol-induced blood brain barrier disruption.

Purpose: Diffusion-weighted arterial spin labeling (DW-ASL) MRI has been proposed to determine the rate of water exchange (K) across the blood brain barrier (BBB). This study aims to further evaluate K MRI by comparing it with standard dynamic contrast-enhanced (DCE) MRI and histology in association with mannitol-induced disruption of the BBB.

Methods: DW-ASL was measured using a multiple b-value MRI protocol in normal rats at three post-labeling delays (N = 19), before and after intra-carotid injection of mannitol to disrupt BBB in one hemisphere (N = 13).

Impacto - A single-arm open-label pilot trial of a digital-based integrated smoking cessation program for Spanish-speaking Hispanic individuals who smoke: Development, feasibility, engagement, and clinical outcomes.

Introduction: Hispanic/Latinx (hereafter Hispanic) individuals who smoke have challenges in quitting and a disproportionate risk of smoking-related health problems when compared to the general population. The smoking inequalities among the Hispanic population are influenced by limited treatment access and chronic stress exposure (e.g.

Rhythm is essential: Unraveling the relation between the circadian clock and cancer.

Physiological processes such as the sleep-wake cycle, metabolism, hormone secretion, neurotransmitter release, sensory capabilities, and a variety of behaviors, including sleep, are controlled by a circadian rhythm adapted to 24-hour day-night periodicity. Disruption of circadian rhythm may lead to the risks of numerous diseases, including cancers. Several epidemiological and clinical data reveal a connection between the disruption of circadian rhythms and cancer.

The Full Range of Weight Status by Race and Ethnicity in Children with and without Autism: A Cross-sectional Study of US Children.

Objective: To identify and characterize how race and ethnicity influence the relationship between autism and weight status, across all categories of weight from underweight to severe obesity.

Study Design: We developed a propensity score-matched cross-sectional dataset of children with and without parent-reported autism in the National Survey of Children Health (NSCH, 2016-2022) and Adolescent Brain and Cognition Development Study (ABCD, 2016-2018). We included non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, and Hispanic children aged 6 to 17 years.

Pulsed Field Ablation in the Elderly via a Pentaspline Multielectrode Catheter: Safety, Efficacy, and Comparison with Cryoballoon and Radiofrequency Devices.

Background: Catheter ablation is an effective treatment for atrial fibrillation (AF). Pulsed field ablation (PFA) has emerged as a novel energy modality, which relies on high-voltage electric fields to achieve cardiac tissue ablation. Data on its efficacy in the elderly are scarce.

Characterizing the relationship between personality dimensions and psychosis-specific clinical characteristics.

Background: Past studies associating personality with psychosis have been limited by small nonclinical samples and a focus on general symptom burden. This study uses a large clinical sample to examine personality's relationship with psychosis-specific features and compare personality dimensions across clinically and neurobiologically defined categories of psychoses.

Methods: A total of 1352 participants with schizophrenia, schizoaffective disorder, and bipolar with psychosis, as well as 623 healthy controls (HC), drawn from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (BSNIP-2) study, were included.

Triangular Fibrocartilage Complex: An Anatomical and Medical Illustration Study.

Recent advances in small-joint arthroscopy and cutting-edge magnetic resonance imaging systems have enabled orthopedic surgeons to perform more complex repairs of the wrist. Such repairs can include those of the triangular fibrocartilage complex (TFCC) of the wrist that necessitates a reappraisal of its morphometry with special emphasis on the relationship between its articular disc (AD) and surrounding tissues. The TFCC AD is a fibrocartilaginous, biconcave structure located between the ulnar styloid process and the carpal bones of the wrist.