Larsucosterol for the Treatment of Alcohol-Associated Hepatitis.

Background: Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy.

Methods: In this phase 2b trial, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized. All patients received supportive care as determined by investigators.

Financial incentives for physical activity in adults: Systematic review and meta-analysis update.

Objective: To update the evidence on the effects of financial incentives (FI) on physical activity (PA) in adults.

Methods: A systematic search of nine databases (Medline, EMBASE, PsychINFO, Scopus, Web of Science, CINAHL, EconLit, SPORTDiscus, and Cochrane) was conducted to identify randomised controlled trials (RCTs) and pilot RCTs published between June 1, 2018 and March 31, 2024 examining FI-for-PA interventions. 'Vote counting' and random-effects meta-analyses assessed short- (<6 months) and long-term (≥6 months) FI effects, as well as impact during follow-up (incentive withdrawal).

Nurses' Perceptions of the Relevance of Their Role and Responsibilities for Adopting Evidence-Based Feedback Into Practice: An Implementation Study.

Aims: To evaluate the implementation process of a novel program focused on improving interactive (dialogic) feedback between clinicians and students during placement.

Design: Quantitative cross-sectional hybrid type 3 effectiveness-implementation study driven by a federated model of social learning theory and implementation theory.

Methods: From June to November 2018, feedback approaches supported by socio-constructive learning theory and Normalisation Process Theory were enacted in four clinical units of a healthcare facility in southeast Queensland, Australia.

Branched endosomal disruptor (BEND) lipids mediate delivery of mRNA and CRISPR-Cas9 ribonucleoprotein complex for hepatic gene editing and T cell engineering.

Lipid nanoparticles (LNPs) are the preeminent non-viral drug delivery vehicle for mRNA-based therapies. Immense effort has been placed on optimizing the ionizable lipid (IL) structure, which contains an amine core conjugated to lipid tails, as small molecular adjustments can result in substantial changes in the overall efficacy of the resulting LNPs. However, despite some advancements, a major barrier for LNP delivery is endosomal escape.

What Veterinarians Need to Know About the Newly-Emerging Field of Insects-as-Food-and-Feed.

Over the last two decades, the insects-as-food-and-feed industry has rapidly emerged. Its growth is largely because insects require substantially less resources (water, food, and energy) to produce than traditional sources of animal protein, making it a sustainable alternative food option. As this industry continues to grow, veterinarians will likely be called upon to assist in identifying food safety concerns, assessing animal health, implementing biosecurity measures, and formulating/prescribing treatment protocols comparable to what we have seen with the honeybee industry and the institution of veterinary feed directives (VFDs).

Human iPSC Reprogramming Success: The Impact of Approaches and Source Materials.

Since their discovery, human induced pluripotent stem cells (hiPSCs) have been instrumental in biomedical research, particularly in the fields of disease modelling, drug screening and regenerative therapies. Their use has significantly increased over recent years driven by the ability of hiPSCs to provide differentiated cell models without requiring embryonic stem cells. Furthermore, the transition from integrating to non-integrating reprogramming methodologies has contributed to the increase in utilisation.

Lack of Competence of US Mosquito Species for Circulating Oropouche Virus.

Given recent outbreaks of Oropouche virus in Latin America and >100 confirmed travel-associated cases in the United States, we evaluated the competence of US vectors, including Aedes albopictus, Culex quinquefasciatus, Culex pipiens, and Anopheles quadrimaculatus mosquitoes. Results with historic and recent isolates suggest transmission potential for those species is low.

The gendered nature of leader behaviors: Navigating stereotype threat from conservation of resources and gender role perspectives.

Previous research has highlighted the benefits followers gain from their leaders' initiating structure and consideration. Adopting a leader-centric perspective, we propose that leaders' gender influences the impact of these behaviors for leaders themselves. Drawing from conservation of resources and gender role theories, we explain why gender-role-inconsistent leader behaviors (behaviors that go against gender stereotypes, such as initiating structure for women and consideration for men) is detrimental, while engaging in gender-role-consistent leader behaviors (such as initiating structure for men and consideration for women) is beneficial.

Prospective Trial of a Passive Diversion Device to Reduce Blood Culture Contamination.

Background: Blood culture contaminants can lead to inappropriate antibiotic use, prolonged length of stay, and additional hospital costs. Several devices have been developed to reduce the risk of blood culture contamination by diverting a portion of the initial blood sample from the blood culture bottle. We assessed the effectiveness of 1 blood diversion device (BDD) in a prospective trial performed at the 2 separate emergency departments (EDs) of an academic medical center.

Disparities in Alcohol-Associated Liver Disease Hospital Encounters Amongst a Texas-Based Cohort of Patients.

Introduction: Alcohol-associated liver disease (ALD) disproportionately impacts men, racial and ethnic minorities, and individuals of low socioeconomic status; however, it's unclear how recent increases in ALD burden have impacted these disparities. We aimed to describe trends in racial, ethnic and socioeconomic disparities in alcohol-associated hospital encounters.

Methods: We conducted a retrospective cohort study of adult hospital encounters with alcohol-associated diagnoses from three health systems between January 2016 and December 2021.

Community Implementation and Evaluation of the Chicago Parent Program.

The purpose of this study was to describe and evaluate the implementation of the Chicago Parent Program (CPP) in a community setting. Included are details of the co-designed implementation by academic and community partners, and parenting and child behavior outcomes. Two hundred eighty caregivers of children aged 2-5 years participated in the CPP in seven community sites.

Patient centered medication treatment for opioid use disorder in rural Vermont: a qualitative study.

Background: Opioid-related fatal overdoses are occurring at historically high levels and increasing each year. Accessible social and financial support are imperative to the initiation and success of treatment for Opioid Use Disorder (OUD). Medications for Opioid Use Disorder (MOUD) offer effective treatment but there are many more people with untreated OUD than receiving evidence-based medication.

Evaluation of a Point-of-Care-Viscoelastic Coagulation Device in Hispaniolan Amazon Parrots ().

Viscoelastic testing evaluates the formation and lysis of a clot over time, allowing more complete assessment of patient hemostasis in real time, whereas traditional tests, such as prothrombin time and partial thromboplastin time, only measure coagulation factor function. Patient-side viscoelastic coagulation monitors are easy to use, portable, and provide faster turnaround time than commercial laboratories. Viscoelastic testing requires only 0.

Solution biophysics identifies lipid nanoparticle non-sphericity, polydispersity, and dependence on internal ordering for efficacious mRNA delivery.

Lipid nanoparticles (LNPs) are the most advanced delivery system currently available for RNA therapeutics. Their development has accelerated since the success of Patisiran, the first siRNA-LNP therapeutic, and the mRNA vaccines that emerged during the COVID-19 pandemic. Designing LNPs with specific targeting, high potency, and minimal side effects is crucial for their successful clinical use.

Increasing and maintaining rates of standardized depression screening in youth with childhood-onset systemic lupus erythematosus in a pediatric rheumatology clinic.

Background: Depression adversely affects health outcomes in patients with childhood-onset systemic lupus erythematous (cSLE). By identifying patients with depressive symptoms, we can intervene early with referrals to mental health resources and improve outcomes. The aim of our quality improvement project was to increase and maintain rates of standardized depression screening for youth with cSLE seen within our pediatric rheumatology clinic.

Multiarm-Assisted Design of Dendron-like Degradable Ionizable Lipids Facilitates Systemic mRNA Delivery to the Spleen.

Lipid nanoparticles (LNPs) have emerged as pivotal vehicles for messenger RNA (mRNA) delivery to hepatocytes upon systemic administration and to antigen-presenting cells following intramuscular injection. However, achieving systemic mRNA delivery to non-hepatocytes remains challenging without the incorporation of targeting ligands such as antibodies, peptides, or small molecules. Inspired by comb-like polymeric architecture, here we utilized a multiarm-assisted design to construct a library of 270 dendron-like degradable ionizable lipids by altering the structures of amine heads and multiarmed tails for optimal mRNA delivery.

Robust, Scalable Microfluidic Manufacturing of RNA-Lipid Nanoparticles Using Immobilized Antifouling Lubricant Coating.

Despite the numerous advantages demonstrated by microfluidic mixing for RNA-loaded lipid nanoparticle (RNA-LNP) production over bulk methods, such as precise size control, homogeneous distributions, higher encapsulation efficiencies, and improved reproducibility, their translation from research to commercial manufacturing remains elusive. A persistent challenge hindering the adoption of microfluidics for LNP production is the fouling of device surfaces during prolonged operation, which significantly diminishes performance and reliability. The complexity of LNP constituents, including lipids, cholesterol, RNA, and solvent mixtures, makes it difficult to find a single coating that can prevent fouling.

EFFECT OF DIPOTASSIUM ETHYLENEDIAMINETETRAACETIC ACID AND LITHIUM HEPARIN ANTICOAGULANT ON HEMATOLOGIC VALUES IN THE BEARDED DRAGON () IN A CLINICAL SETTING.

Anticoagulant choice can have significant effect on complete blood counts of reptiles and has not been reported in bearded dragons (). Whole blood was collected from 14 captive individuals and aliquoted into separate blood tubes containing dipotassium ethylenediaminetetraacetic acid (EDTA) and lithium heparin. Samples were shipped and processed within 24 h.

An automated treatment planning portfolio for whole breast radiotherapy.

Background: Automation in radiotherapy presents a promising solution to the increasing cancer burden and workforce shortages. However, existing automated methods for breast radiotherapy lack a comprehensive, end-to-end solution that meets varying standards of care.

Purpose: This study aims to develop a complete portfolio of automated radiotherapy treatment planning for intact breasts, tailored to individual patient factors, clinical approaches, and available resources.

A comparative analysis of small extracellular vesicle (sEV) micro-RNA (miRNA) isolation and sequencing procedures in blood plasma samples.

Aims: Analysis of miRNA (18-23nt) encapsulated in small extracellular vesicles (sEVs) (diameter ~30-200 nm) is critical in understanding the diagnostic and therapeutic value of sEV miRNA. However, various sEV enrichment techniques yield different quantities and qualities of sEV miRNA. Here, we compare the efficacy of three sEV isolation techniques in four combinations for miRNA next-generation sequencing.

Maximally efficient exchange in thin flow cells using density gradients.

Flow cells are ubiquitous in laboratories and automated instrumentation, and are crucial for ease of sample preparation, analyte addition and buffer exchange. The assumption that the fluids have exchanged completely in a flow cell is often critical to data interpretation. This article describes the buoyancy effects on the exchange of fluids with differing densities or viscosities in thin, circular flow cells.

An interprofessional multicomponent intervention to improve end-of-life care in intensive care: A before-and-after study.

Background: The provision of end-of-life care (EOLC) is an ongoing component of practice in intensive care units (ICUs). Interdisciplinary, multicomponent interventions may enhance the quality of EOLC for patients and the experience of family members and ICU clinicians during this period.

Objectives: This study aimed to assess the impact of a multicomponent intervention on EOLC practices in the ICU and family members' and clinicians' perceptions of EOLC.

Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain.

Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due to the blood-brain barrier (BBB) and the tendency of delivery vehicles to accumulate in the liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA delivery to the brain. We utilize click chemistry to functionalize LNPs with peptides that target receptors overexpressed on brain endothelial cells and neurons, namely the RVG29, T7, AP2, and mApoE peptides.

Wearable Technology and Chronic Illness: Balancing Justice and Care Ethics.

The management of chronic diseases has been revolutionized by the advent of wearable health technology. These devices provide personalized and real-time health data to patients. The problem that this technology is most frequently used to address is obesity and its consequences, heart disease, and certain cancers.