Whole-Body Physiologically Based Pharmacokinetic Modeling of GalNAc-Conjugated siRNAs.

: N-acetyl-galactosamine small interfering RNAs (GalNAc-siRNA) are an emerging class of drugs due to their durable knockdown of disease-related proteins. Direct conjugation of GalNAc onto the siRNA enables targeted uptake into hepatocytes via GalNAc recognition of the Asialoglycoprotein Receptor (ASGPR). With a transient plasma exposure combined with a prolonged liver half-life, GalNAc-siRNA exhibits distinct disposition characteristics.

Competitive displacement of lipoprotein lipase from heparan sulfate is orchestrated by a disordered acidic cluster in GPIHBP1.

Movement of lipoprotein lipase (LPL) from myocytes or adipocytes to the capillary lumen is essential for intravascular lipolysis and plasma triglyceride homeostasis-low LPL activity in the capillary lumen causes hypertriglyceridemia. The trans-endothelial transport of LPL depends on ionic interactions with GPIHBP1's intrinsically disordered N-terminal tail, which harbors two acidic clusters at positions 5-12 and 19-30. This polyanionic tail provides a molecular switch that controls LPL detachment from heparan sulfate proteoglycans (HSPGs) by competitive displacement.

Perceptions of access to harm reduction services during the COVID-19 pandemic among people who inject drugs in metropolitan Chicago.

Background: The COVID-19 pandemic amplified the risk environment for people who inject drugs (PWID), making continued access to harm reduction services imperative. Research has shown that some harm reduction service providers were able to continue to provide services throughout the pandemic. Most of these studies, however, focused on staff perspectives, not those of PWID.

Metabolic and Hormonal Responses to Isomaltulose Ingestion Before or During Sustained Submaximal Exercise in Adults with Type 1 Diabetes Using Automated Insulin Delivery Systems.

Objectives: This article compares metabolic, pancreatic, and gut-derived hormone responses to isomaltulose ingestion, before versus during submaximal sustained exercise, in adults with type 1 diabetes (T1D) using automated insulin delivery systems.

Methods: In a randomized, cross-over trial, eight participants with T1D being treated with automated insulin pumps (five females, age: 47 ± 16 years, BMI: 27.5 ± 3.

Associations between mental illness, TB risk and migrant status.

Background: TB and mental illnesses are public health priorities that often co-exist, with migrants in high-income countries being at risk for both conditions. This study investigates whether mental illness influences TB risk and examines the impact of migration status.

Methods: A nationwide prospective cohort study was conducted in Denmark from 1994-2015, involving migrants matched 1:6 to Danish-born individuals.

Influence of Germicidal UV (222 nm) Lamps on Ozone, Ultrafine Particles, and Volatile Organic Compounds in Indoor Office Spaces.

Germicidal ultraviolet lamps with a peak emission at 222 nm (GUV222) are gaining prominence as a safe and effective solution to reduce disease transmission in occupied indoor environments. While previous studies have reported O production from GUV222, less is known about their impact on other indoor constituents affecting indoor air quality, especially in real occupied environments. In this study, the effects of GUV222 on the levels of ozone (O), ultrafine particles (UFPs), and volatile organic compounds (VOCs) were investigated across multiple offices with varying occupancies.

Assessment of Clinical Toxicological Resources in Countries Belonging to the World Health Organization's Regional Office of the Eastern Mediterranean.

Introduction: Poison Centers are vital to prevent and manage exposures to chemicals, toxins, and ionizing radiation. However, many countries still lack sufficient poison information center services. Within the World Health Organization's Eastern Mediterranean Regional Office (EMRO) region, we were not able to identify a formal assessment of its toxicological resources.

Large-Language Models in Orthodontics: Assessing Reliability and Validity of ChatGPT in Pretreatment Patient Education.

Background: Patients seeking orthodontic treatment may use large language models (LLMs) such as Chat-GPT for self-education, thereby impacting their decision-making process. This study assesses the reliability and validity of Chat-GPT prompts aimed at informing patients about orthodontic side effects and examines patients' perceptions of this information.

Materials And Methods: To assess reliability, n = 28 individuals were asked to generate information from GPT-3.

Correction: Fetal overgrowth in women with type 1 and type 2 diabetes mellitus.

[This corrects the article DOI: 10.1371/journal.pone.

Na/H-exchange inhibition by cariporide is compensated via Na,HCO-cotransport and has no net growth consequences for ErbB2-driven breast carcinomas.

Defense against intracellular acidification of breast cancer tissue depends on net acid extrusion via Na,HCO-cotransporter NBCn1/Slc4a7 and Na/H-exchanger NHE1/Slc9a1. NBCn1 is increasingly recognized as breast cancer susceptibility protein and promising therapeutic target, whereas evidence for targeting NHE1 is discordant. Currently, selective small molecule inhibitors exist against NHE1 but not NBCn1.

Speech Recognition and Spatial Hearing in Young Adults With Down Syndrome: Relationships With Hearing Thresholds and Auditory Working Memory.

Objectives: Individuals with Down syndrome (DS) have a higher incidence of hearing loss (HL) compared with their peers without developmental disabilities. Little is known about the associations between HL and functional hearing for individuals with DS. This study investigated two aspects of auditory functions, "what" (understanding the content of sound) and "where" (localizing the source of sound), in young adults with DS.

INfluenza VaccInation To mitigate typE 1 Diabetes (INVITED): a study protocol for a randomised, double-blind, placebo-controlled clinical trial in children and adolescents with recent-onset type 1 diabetes.

Introduction: Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last months to years. Preserving β-cell function can reduce T1D complications and improve glycaemic control. Influenza vaccination has pleiotropic effects and administration of the vaccine during the early phases of T1D may offer β-cell protection.

Mechanisms underlying the development of eating disorders and disordered eating in adolescent females with type 1 diabetes.

Objective: People with Type 1 diabetes (T1D) face an increased risk of eating disorders/disordered eating (ED/DE), with adolescents being particularly vulnerable. Empirical knowledge on the mechanisms underlying development of ED/DE in T1D is crucial for evolving prevention strategies.

Research Design And Methods: Fourteen semi-structured interviews with adolescent females with T1D and ED/DE between 14 and 18 years were conducted and analyzed using reflexive thematic analysis.

Detection of volatile hydroperfluoroalkanes during hydrothermal liquefaction of perfluoroalkyl carboxylic acids at circumneutral pH.

Hydrothermal liquefaction (HTL) is a promising technology for converting wet organic waste such as sewage sludge into biocrude oil while simultaneously destroying per- and polyfluoroalkyl substances (PFAS). This study tracked the fate and degradation of six representative PFAS in water to address the effect of perfluoroalkyl chain length on degradation rates and the formation of volatile transformation products at 300-350 °C. While perfluorosulfonic acids were recalcitrant, perfluoroalkyl carboxylic acids (PFCAs) were rapidly and completely decarboxylated to hydroperfluoroalkanes (1 H-perfluoroheptane in the case of perfluorooctanoic acid).

Improving quality and patient safety in surgical care through standardisation and harmonisation of perioperative care (SAFEST project): A research protocol for a mixed methods study.

Introduction: Adverse events in health care affect 8% to 12% of patients admitted to hospitals in the European Union (EU), with surgical adverse events being the most common types reported.

Aim: SAFEST project aims to enhance perioperative care quality and patient safety by establishing and implementing widely supported evidence-based perioperative patient safety practices to reduce surgical adverse events.

Methods: We will conduct a mixed-methods hybrid type III implementation study supporting the development and adoption of evidence-based practices through a Quality Improvement Learning Collaborative (QILC) in co-creation with stakeholders.

Assessment of visual problems after acquired brain injury: a survey of current practice in Danish hospitals.

Objectives: To explore current hospital practice in relation to the assessment of vision problems in patients with acquired brain injury.

Design: A survey study.

Subjects: A total of 143 respondents from hospital settings, with background in occupational therapy and physical therapy, participated in the survey.

Tuning the double lipidation of salmon calcitonin to introduce a pore-like membrane translocation mechanism.

A widespread strategy to increase the transport of therapeutic peptides across cellular membranes has been to attach lipid moieties to the peptide backbone (lipidation) to enhance their intrinsic membrane interaction. Efforts in vitro and in vivo investigating the correlation between lipidation characteristics and peptide membrane translocation efficiency have traditionally relied on end-point read-out assays and trial-and-error-based optimization strategies. Consequently, the molecular details of how therapeutic peptide lipidation affects it's membrane permeation and translocation mechanisms remain unresolved.