Effect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβ Alzheimer Disease Mouse Model.

Alzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.

Implementation of Ambulatory Kidney Supportive Care in a Safety Net Hospital.

Context: Chronic kidney disease (CKD) disproportionately impacts lower socioeconomic groups and is associated with many symptoms and complex decisions. Integration of Kidney Supportive Care (KSC) with CKD care can address these needs. To our knowledge, this approach has not been described in an underserved population.

Association between dietary fructose and human colon DNA methylation: implication for racial disparities in colorectal cancer risk using a cross-sectional study.

Background: An increasing body of evidence has linked fructose intake to colorectal cancer (CRC). African American (AA) adults consume greater quantities of fructose and are more likely to develop right-side colon cancer than European American (EA) adults.

Objective: We examined the hypothesis that fructose consumption leads to epigenomic and transcriptomic differences associated with CRC tumor biology.

Pulsed Ultrasound-Mediated Drug Delivery Enhancement Through Human Sclera.

Purpose: The purpose of this study was to characterize whether pulsed ultrasound (PUS) affects transscleral drug delivery.

Methods: Fluorescein sodium (NaF, 376 Da) and fluorescein isothiocyanate-conjugated dextran 40 (FD-40, 40 kDa) were used as model drugs. Human sclera grafts were placed in modified Franz diffusion cells and were treated by PUS (1 megahertz [MHz], 0.

Understanding the Role of Trust in Healthcare and Intentions to Pursue Live Donor Kidney Transplant Among African American End Stage Kidney Disease Patients.

African Americans (AAs) with end-stage kidney disease (ESKD) experience significant barriers to accessing living donor kidney transplantation (LDKT), largely due to individual and systemic factors, including a lack of trust in healthcare systems resulting from a legacy of and continued experiences with medical racism. This cross-sectional study analyzed survey data from 416 AA patients with ESKD undergoing transplant evaluation in 2019-2023 at two kidney transplant centers in the Southeast United States, examining whether trust (specifically trust in kidney doctors, hospitals, and healthcare) modifies the relationship between attitudes towards LDKT and behavioral intentions to discuss LDKT with family and friends. Multivariable analyses revealed significant interactions.

Central Nervous System Metastases in Breast Cancer.

Breast cancer metastasizing to the central nervous system (CNS) encompasses two distinct entities: brain metastases involving the cerebral parenchyma and infiltration of the leptomeningeal space, i.e., leptomeningeal disease.

CD4+ T helper 2 cell-macrophage crosstalk induces IL-24-mediated breast cancer suppression.

CD4+ T cells contribute to antitumor immunity and are implicated in the efficacy of cancer immunotherapies. In particular, CD4+ T helper 2 (Th2) cells were recently found to block spontaneous breast carcinogenesis. However, the antitumor potential of Th2 cells in targeting established breast cancer remains uncertain.

COMT and MTHFR Genetic Variants Combined Effects on Adolescent Idiopathic Scoliosis Progression.

Genetic variants encoding both low COMT and MTHFR activity are associated with idiopathic scoliosis. The combined impact of and on progression of adolescent idiopathic scoliosis (AIS) is unknown. This study investigated if and low activity variants are associated with AIS progression.

Arachidonic acid synergizes with aspirin preventing myocardial ischemia-reperfusion injury and mitigates bleeding risk.

Aims: The therapeutic efficacy of coronary revascularization is compromised by myocardial ischemia-reperfusion (MI/R) injury. Higher levels of circulating arachidonic acid (AA) are reportedly associated with lower risk of cardiovascular disease. The cyclooxygenase (COX) pathway metabolizes AA into prostaglandins (PGs) and the platelet-activating thromboxane A2 (TXA2), which is inhibited by aspirin.

The Role of Double-Zero-Event Studies in Evidence Synthesis: Evaluating Robustness Using the Fragility Index.

Rationale: Zero-event counts are common in clinical studies, particularly when assessing rare adverse events. These occurrences can result from low event rates, short follow-up periods, and small sample sizes. When both intervention and control groups report zero events in a clinical trial, the study is referred to as a double-zero-event study, which presents methodological challenges for evidence synthesis.

Impact of Social Determinants of Health on Pre-exposure Prophylaxis Care for HIV Prevention.

Background: HIV continues to disproportionately impact men who have sex with men (MSM) in the United States (US). Pre-exposure prophylaxis (PrEP) is effective, but disparities persist. Limited studies have conducted systematic evaluations of social determinants of health (SDOH) and their effects on PrEP persistence among MSM.

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.

Network analysis combined with genome-wide association study helps identification of genes related to amino acid contents in soybean.

Background: Additional to total protein content, the amino acid (AA) profile is important to the nutritional value of soybean seed. The AA profile in soybean seed is a complex quantitative trait controlled by multiple interconnected genes and pathways controlling the accumulation of each AA. With a total of 621 soybean germplasm, we used three genome-wide association study (GWAS)-based approaches to investigate the genomic regions controlling the AA content and profile in soybean.

Medical large language models are vulnerable to data-poisoning attacks.

The adoption of large language models (LLMs) in healthcare demands a careful analysis of their potential to spread false medical knowledge. Because LLMs ingest massive volumes of data from the open Internet during training, they are potentially exposed to unverified medical knowledge that may include deliberately planted misinformation. Here, we perform a threat assessment that simulates a data-poisoning attack against The Pile, a popular dataset used for LLM development.

Toward expert-level medical question answering with large language models.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

Harmonization of alcohol use data and mortality across a multi-national HIV cohort collaboration.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).

Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration.

Pregnenolone effects on parasympathetic response to stress and alcohol cue provocation in treatment-seeking individuals with alcohol use disorder.

Background: Chronic alcohol consumption in alcohol use disorder (AUD) is associated with autonomic nervous system dysregulation, increasing cardiovascular risk, and high alcohol cravings. Heart rate variability (HRV), a marker of autonomic nervous system responsiveness to stressors, may mediate alcohol's impact on the cardiovascular system. While pregnenolone (PREG) has been shown to normalize heart rate and blood pressure in individuals with AUD, its effects on sympathetic and parasympathetic components of HRV and related alcohol craving are not known.

Association of Systemic Thromboxane Generation With Risk of Developing Heart Failure.

Background: Systemic thromboxane A generation, which is readily assessed by quantifying thromboxane B metabolites (TXB-M) in the urine, is associated with impaired cardiac performance and mortality in aspirin (ASA) users with heart failure (HF).

Objectives: This study sought to determine the association of urinary TXB-M with the risk of developing HF in individuals without prior history of HF and with normal left ventricular function irrespective of ASA use.

Methods: Urine TXB-M were measured by immunoassay and adjusted to urine concentration and renal function (TXB-M) in 2,611 Framingham Heart Study participants (54.

Does cyber dating abuse victimization predict next-day alcohol and cannabis use among college students?

Background And Objectives: Cyber dating abuse (CDA) is prevalent on college campuses, with 43% of college students experiencing CDA each year. Yet, the potential impacts of CDA victimization on college students' health outcomes remain poorly understood. Informed by the self-medication hypothesis and longitudinal data linking dating abuse to substance use outcomes, the present study tested the hypothesis that CDA victimization positively associates with college students' next-day alcohol use (number of drinks consumed, odds of any drinking) and odds of cannabis use (yes/no).

The MR1/MAIT cell axis enhances dystrophic neurite development in Alzheimer's disease.

Introduction: Plaques are a hallmark feature of Alzheimer's disease (AD). We found that the loss of mucosal-associated invariant T (MAIT) cells and their antigen-presenting molecule MR1 caused a delay in plaque pathology development in AD mouse models. However, it remains unknown how this axis is impacting dystrophic neurites.

Increased Risk of Patellofemoral Instability Events and Surgical Management in Patients With Joint Hypermobility Syndromes: A Matched Cohort Analysis.

Purpose: To compare the odds of patellofemoral instability events requiring subsequent surgery and revision surgical intervention in patients with joint hypermobility syndromes (JHS) to that of a matched cohort.

Methods: This is a retrospective cohort study using the PearlDiver Mariner Database. Records were queried between 2010 and 2021 with a diagnosis of JHS, including Ehlers-Danlos syndrome (EDS) and Marfan syndrome.

Both English- and Spanish-Language Anterior Cruciate Ligament Reconstruction Online Patient Education Materials Are Written at Higher-Than-Recommended Reading Levels.

Purpose: To examine the overall reading levels of anterior cruciate ligament reconstruction online patient education materials (OPEMs) written in English and Spanish.

Methods: We conducted Google searches for OPEMs using "ACL surgery" and "" as English and Spanish search terms, respectively. Several measures of readability were used to analyze 25 English-language OPEMs (Flesch Reading Ease, Flesch Reading Ease Grade Level, Flesch-Kincaid Grade Level, Coleman-Liau Index, Gunning Fog Index, and Simple Measure of Gobbledygook) and 25 Spanish-language OPEMs (Fernández-Huerta Index, Fernández-Huerta Grade Level, and Índice de Legibilidad de Flesch-Szigriszt).

The etiology and prevention of early-stage tau pathology in higher cortical circuits: Insights from aging rhesus macaques.

Aging rhesus macaques provide a unique model for learning how age and inflammation drive early-stage pathology in sporadic Alzheimer's disease, and for testing potential therapeutics. Unlike mice, aging macaques have extensive association cortices and inflammatory signaling similar to humans, are apolipoprotein E ε4 homozygotes, and naturally develop tau and amyloid pathology with marked cognitive deficits. Importantly, monkeys provide the unique opportunity to study early-stage, soluble hyperphosphorylated tau (p-tau), including p-tau217.

Plasma p-tau and neurofilament/p-tau ratio in differentiating Alzheimer's disease from syndromes associated with frontotemporal lobar degeneration.

Introduction: Plasma-based biomarkers have shown promise for clinical implementation, but their accuracy in differentiating Alzheimer's disease (AD) from syndromes associated with frontotemporal lobar degeneration (FTLD) has yet to be fully investigated. This study assessed the potential of plasma biomarkers for differential diagnosis.

Methods: This cohort study included 374 participants (96 AD, 278 FTLD).