Alzheimer's disease risk ABCA7 p.A696S variant disturbs the microglial response to amyloid pathology in mice.

The adenosine triphosphate-binding cassette transporter A7 (ABCA7) gene is ranked as one of the top susceptibility loci for Alzheimer's disease (AD). While ABCA7 mediates lipid transport across cellular membranes, ABCA7 loss of function has been shown to exacerbate amyloid-β (Aβ) pathology and compromise microglial function. Our family-based study uncovered an extremely rare ABCA7 p.

Variable peptide processing of a Conus (Asprella) neocostatus α-conotoxin generates bioactive toxiforms that are potent against distinct nicotinic acetylcholine receptor subtypes.

Conusvenoms are composed of peptides that are commonly post-translationally modified, increasing their chemical diversity beyond what is encoded in the genome and enhancing their potency and selectivity. This study describes how PTMs alter an α-conotoxin's selectivity for specific nAChR subtypes. Venom from the cone snailConus(Asprella)neocostatuswas fractionated using high-performance liquid chromatography and tested using a behavioral intracranial mouse bioassay and a cholinergic calcium imaging assay using SH-SY5Y neuroblastoma cells.

Anaphylaxis definition, overview, and clinical support tool: 2024 consensus report.

Background: The 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) anaphylaxis criteria are widely used in clinical care and research. In 2020, the World Allergy Organization (WAO) published modified criteria that have not been uniformly adopted. Different criteria contribute to inconsistent care and research outcomes.

FLASH proton reirradiation, with or without hypofractionation, reduces chronic toxicity in the normal murine intestine, skin, and bone.

Background And Purpose: The normal tissue sparing afforded by FLASH radiotherapy is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton radiotherapy (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated.

Consuming Pecans as a Snack Improves Lipids/Lipoproteins and Diet Quality Compared to Usual Diet in Adults at Increased Risk for Cardiometabolic Diseases: A Randomized Controlled Trial.

Background: The vascular and cardiometabolic effects of pecans are relatively under-studied.

Objectives: The aim was to examine how substitution of usual snack foods with 57 g/day of pecans affects vascular health, risk factors for cardiometabolic diseases and diet quality, compared to continuing usual intake in individuals at risk for cardiometabolic diseases.

Methods: A 12-week single-blinded, parallel, randomized controlled trial was conducted.

Advancing Cancer Diagnosis and Treatment: Integrating Molecular Biomarkers and Emerging Technologies.

Cancer biomarkers can be derived from tumor cells or neighboring cells within the tumor microenvironment. Over the past few decades, various molecular markers, including DNA (mutations, copy number variations), RNA (mRNA, microRNA, circular RNA), proteins, and metabolites, have been identified with the aid of rapidly evolving technologies. Some of these markers have demonstrated potential clinical utility, while others have provided new insights into the deregulation of normal molecular and cellular processes that lead to tumorigenesis.

What apps and websites do those in treatment for substance-related problems use to help them in their recovery? A cross-sectional study of products and use patterns.

Background: Given the global burden of substance use disorders (SUD), innovations in methods to achieve sustained recovery are critical. Digital health products (e.g.

Omniflow prosthesis for treatment prosthetic graft infection of the aorto-iliac and femoropopliteal level on the infrarenal aortic segment and lower extremity.

Objectives: To report outcomes after the use of the Omniflow II biosynthetic graft (LeMaitre Vascular, Il, USA) for vascular reconstruction in patients with prosthetic infection at the aorto-iliac and femoropopliteal level.

Methods: Within a six-year period, all consecutive patients with aorto-iliac and femoro-popliteal graft infection treated by resection of the infected graft material, extensive local debridement and reconstruction using Omniflow II biosynthetic graft were retrospectively analzyed. Patient characteristics, intraoperative details, postoperative outcomes, and infection details were assessed.

Trehalose decorated nanostructures stabilize combined cross-linked enzyme aggregates (Combi-CLEAs) of β-galactosidase and glucose isomerase.

Combined cross-linked enzyme aggregates (Combi-CLEAs) of β-Galactosidase (β-Gal) and Glucose Isomerase (GI) allow the transformation of d-lactose to lactose-fructose syrup through one-pot cascade biocatalytic reactions. Despite its promise, the low thermostability of β-Gal and high-temperature demands for GI limits this application. Trehalose is a protein-stabilizing disaccharide which has been utilized in immobilized enzyme systems to enhance protein thermostability.

Comparison between Global Leadership Initiative on Malnutrition criteria and protein-energy wasting in patients with kidney failure undergoing peritoneal dialysis.

Background: Protein-energy wasting (PEW) is the chronic kidney disease (CKD)-specific diagnosis encompassing malnutrition. PEW is associated with adverse outcomes, including those receiving peritoneal dialysis (PD). Identifying PEW requires accurate methods to improve diagnosis.

Bleeding Risk Assessment with Thromboelastography in Interventional Pulmonology Procedures.

Objective: Thromboelastography (TEG) offers a point-of-care and comprehensive evaluation of the coagulation cascade, but its utility in predicting bleeding risk in Interventional Pulmonology (IP) procedures has not been thoroughly investigated. This study aims to evaluate the effectiveness of TEG in assessing bleeding risk in patients undergoing elective IP procedures.

Material And Methods: Retrospective study of patients who underwent elective IP procedures at Mayo Clinic (Jacksonville, FL, USA) from November 2022 to May 2024.

Outcomes of Anesthesia-Supported versus Endoscopist-Driven Sedation Modalities: A retrospective cohort study.

Background And Aims: Anesthesia involvement has become commonplace in many procedural settings. The goal of this study is to compare sedation modalities utilized by endoscopists and anesthesiologists in the endoscopy suite, particularly with respect to recovery time and adverse events.

Methods: We conducted a retrospective cohort study including adults (≥18) undergoing outpatient EGD and/or colonoscopy at Mayo Clinic in Jacksonville, Florida between October 1, 2018 through December 31, 2022.

Interrupting sitting with moderate-intensity physical activity breaks improves cognitive processing speed in adults with overweight and obesity: Findings from the SITLess pilot randomized crossover trial.

Introduction: Prolonged sitting can acutely reduce working memory (WM) in individuals with overweight and obesity (OW/OB) who show executive function deficits. Interrupting prolonged sitting with brief PA bouts may counter these effects. However, the benefits of such interventions on behavioral and neuroelectric indices of WM and whether neurocognitive responses are associated with postprandial glycemic responses in young and middle-aged adults with OW/OB remain unknown.

Dried and Tested: Inoculation Method Impacts Low-Moisture Food Persistent Bacterial Populations.

Pathogen contamination and harborage in low-moisture food (LMF) processing environments have resulted in outbreaks and recalls, but researchers are limited in their abilities to investigate solutions. Methods used in most laboratory studies do not accurately reflect the route of contamination or harborage of pathogens in LMF environments, which complicates studying of sanitation methods. Inoculation methods were compared to establish low-moisture food persistent bacterial populations (LMF PBPs) that realistically reflect populations found in LMF environments.

The Cross-Sectional Association Between Ultra-Processed Food Intake and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background And Aims: The prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease has increased in parallel with a rise in consumption of ultra-processed foods (UPF), but little is known about their association.

Methods: We cross-sectionally examined associations of UPF with hepatic steatosis and fibrosis in 2,458 (mean age 54 years; 55.9% women) community-dwelling adults who completed vibration-controlled transient elastography and a food frequency questionnaire.

Changes in Out-of-Pocket Drug Expenditures Among Medicare Beneficiaries with Dementia Under the Inflation Reduction Act: A Simulation Study.

Objectives: We investigated how the Inflation Reduction Act (IRA) Medicare Part D benefit redesign may reduce out-of-pocket (OOP) drug expenditures for Medicare beneficiaries with dementia. Methods Design Utilizing data from the Health and Retirement Study (HRS) linked with Medicare claims, we simulated post-redesign OOP drug spending by applying the 2025 prescription drug cost-sharing rules to each beneficiary's pre-redesign Part D medication utilization data for 2016, adjusting for inflation. Participants Our study population comprised HRS respondents aged 65 and older in 2016, enrolled in Medicare fee-for-service, with at least one Part D drug claim in 2016, and diagnosed with dementia between 2000 and 2016 (n=1,677).

Pre-clinical Evaluation of New Generation Bridging Stent for Fenestrated Endovascular Aneurysm Repair using Realistic 3D Printed Aneurysm Models.

Objective: The aim of this study was to perform a comparative pre-clinical evaluation of a new fenestrated endovascular aneurysm repair dedicated stent using perfused 3D printed patient anatomies.

Methods: The test setup included a pulsatile pump set to reproduce human haemodynamics, four 3D printed pararenal aneurysms connected to a bench test, and four corresponding fenestrated grafts (Zenith Fenestrated; Cook, Bloomington, IN, USA). Bridging stents were sized based on analysis of patients computed tomography scans and included either four standard covered stents (BeGraft [BG]; Bentley, Hechingen, Germany) or four similar covered stent grafts mounted on a modified balloon to allow stent implantation and flaring in one step (BeFlared [BF]; Bentley).

A benzoxazolyl urea inhibits VraS and enhances antimicrobials against vancomycin intermediate-resistant Staphylococcus aureus.

Vancomycin intermediate-resistant Staphylococcus aureus (VISA) is a pathogen of concern. VraS, a histidine kinase, facilitates the VISA phenotype. Here, we reveal a benzoxazolyl urea (chemical 1) that directly inhibits VraS and enhances vancomycin to below the clinical breakpoint against an archetypal VISA strain, Mu50.

Dietary carbohydrate quality is associated with epigenetic age acceleration: a cross-sectional study of the CARDIA cohort.

Background: Dietary intake is one lifestyle factor that is expected to impact gene expression by altering DNA methylation (DNAm), thus affecting epigenetic aging. Studies on the association between quality of carbohydrates and epigenetic age acceleration (EAA) are scarce despite the evidence that quality may be more important than amount of carbohydrates consumed.

Objective: We aimed to identify the cross-sectional associations of carbohydrate quality and fiber-rich food score with epigenetic age acceleration in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Cholesterol affects the binding of proteins to phosphatidic acid without influencing its ionization properties.

Phosphatidic acid (PA) through its unique negatively charged phosphate headgroup binds to various proteins to modulate multiple cellular events. To perform such diverse signaling functions, the ionization and charge of PA's headgroup relies on the properties of vicinal membrane lipids and changes in cellular conditions. Cholesterol has conspicuous effects on lipid properties and membrane dynamics.

Assessing the Impacts of Drug Loading and Polymer Type on Dissolution Behavior and Diffusive Flux of GDC-6893 Amorphous Solid Dispersions.

It is desirable but remains challenging to develop high drug load amorphous solid dispersions (ASDs) without compromising their quality attributes and bio-performance. In this work, we investigated the impacts of formulation variables, such as drug loading (DL) and polymer type, on dissolution behavior, diffusive flux, and in vitro drug absorption of ASDs of a high T compound, GDC-6893. ASDs with two polymers (HPMCAS and PVPVA) and various DLs (20 - 80%) were produced by spray drying and their drug-polymer miscibility was evaluated using solid-state nuclear magnetic resonance (ssNMR).

Physical Isolation Strategy in Multi-Layer Self-Nanoemulsifying Pellets: Improving Dissolution and Drug Loading Efficiency of Ramipril.

Background And Purpose: Liquid self-nanoemulsifying drug delivery systems (SNEDDS) face challenges related to stability, handling, and storage. In particular, lipophilic and unstable drugs, such as ramipril (RMP) and thymoquinone (THQ), face challenges in oral administration due to poor aqueous solubility and chemical instability. This study aimed to develop and optimize multi-layer self-nanoemulsifying pellets (ML-SNEP) to enhance the stability and dissolution of ramipril (RMP) and thymoquinone (THQ).

Structure and self-association of Arrestin-1.

Arrestins halt cell signaling by binding to phosphorylated activated G protein-coupled receptors. Arrestin-1 binds to rhodopsin, arrestin-4 binds to cone opsins, and arrestins-2,3 bind to the rest of GPCRs. In addition, it has been reported that arrestin-1 is functionally expressed in mouse cone photoreceptors.