Engaging Patients in Discussions About Medication Deprescribing.

Background: Deprescribing, intentional medication discontinuation or dose reduction, can reduce potentially inappropriate medication use and medication-related harms. Engaging patients in deprescribing discussions may increase likelihood of deprescribing and promote shared decision-making.

Objective: To examine the impact of patient-directed educational brochures on patient engagement and deprescribing discussions with primary care providers (PCPs).

Medical management pathways for Cushing's disease in pituitary tumors centers of excellence (PTCOEs).

Purpose: A recent update of consensus guidelines for the management of Cushing's disease (CD) included indications for medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current medical therapy approaches by expert pituitary centers through an audit conducted to validate the criteria of Pituitary Tumors Centers of Excellence (PTCOEs) and provide an initial standard of medical care for CD.

CARD domains mediate anti-phage defence in bacterial gasdermin systems.

Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Following pathogen recognition by nucleotide binding-domain, leucine-rich, repeat-containing (NLR) proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore-forming proteins to induce pyroptotic cell death. Here we show that CARD domains are present in defence systems that protect bacteria against phage.

APOE4 and sedentary lifestyle synergistically impair neurovascular function in the visual cortex of awake mice.

Reduced cerebral blood flow occurs early in the development of Alzheimer's disease (AD), but the factors producing this reduction are unknown. Here, we ask whether genetic and lifestyle risk factors for AD-the ε4 allele of the Apolipoprotein (APOE) gene, and physical activity-can together produce this reduction in cerebral blood flow which leads eventually to AD. Using in vivo two-photon microscopy and haemodynamic measures, we record neurovascular function from the visual cortex of physically active or sedentary mice expressing APOE3 and APOE4 in place of murine APOE.

Categorization of 34 computational methods to detect spatially variable genes from spatially resolved transcriptomics data.

In the analysis of spatially resolved transcriptomics data, detecting spatially variable genes (SVGs) is crucial. Numerous computational methods exist, but varying SVG definitions and methodologies lead to incomparable results. We review 34 state-of-the-art methods, classifying SVGs into three categories: overall, cell-type-specific, and spatial-domain-marker SVGs.

Predicting falls with ultrasound, physical parameters or fall-risk questions among older adults: A prospective cohort study.

Background: Falls are a significant issue among older adults, leading to morbidity and mortality. Screening for fall risk in the ED is crucial but challenging due to time limitations and patient conditions. Sarcopenia, characterized by muscle loss, is associated with increased fall risk, and ultrasound has been proposed as a non-invasive tool to measure muscle mass in this context.

Vasoplegia in Heart, Lung, or Liver Transplantation: A Narrative Review.

Vasoplegia is a pathophysiologic state of hypotension in the setting of normal or high cardiac output and low systemic vascular resistance despite euvolemia and high-dose vasoconstrictors. Vasoplegia in heart, lung, or liver transplantation is of particular interest because it is common (approximately 29%, 28%, and 11%, respectively), is associated with adverse outcomes, and because the agents used to treat vasoplegia can affect immunosuppressive and other drug metabolism. This narrative review discusses the pathophysiology, risk factors, and treatment of vasoplegia in patients undergoing heart, lung, and liver transplantation.

Factors Associated With Short- and Long-Term Survival in Metastatic HER2-Positive Breast Cancer.

Background: We sought to evaluate prognostic factors in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and their relationship with short- and long-term overall survival (OS).

Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we evaluated patients with de novo HER2-positive MBC diagnosed from 2010 to 2018. Univariate analyses were performed to determine effect of each variable on OS.

Currently Available Radiology-Specific Reporting Guidelines.

The aim of this paper is to contextualize and review reporting guidelines available at the EQUATOR Network that are most relevant to radiology-specific investigations. Eight EQUATOR Network reporting guidelines for the clinical area of radiology, not including the subspecialized areas of imaging of the cardiovascular, neurologic, and oncologic diseases are reviewed and discussed. The reporting guidelines are for diagnostic and therapeutic clinical research.

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.

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.

Sequence variants in HECTD1 result in a variable neurodevelopmental disorder.

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy.

Extracellular volume expansion drives vertebrate axis elongation.

The vertebrate bauplan is primarily established via the formation of embryonic tissues in a head-to-tail progression. The mechanics of this elongation, which requires the presomitic mesoderm (PSM), remain poorly understood. Here, we find that avian PSM explants can elongate autonomously when physically confined in vitro, producing a pushing force promoting posterior elongation of the embryo.

Quantitative approaches to structural intersectionality research: Conceptual and methodologic considerations.

There has been a recent influx in the development of novel measures of structural forms of discrimination, including structural racism, xenophobia, sexism, heterosexism, and cisgenderism. These systems of power and oppression are inherently interdependent and mutually constitutive, yet a paucity of research has investigated their joint impacts; this gap is likely reflective of the limited guidance that exists regarding how to effectively combine multiple measures of structural discrimination to examine their joint impacts on population health and health inequities. In this commentary, we seek to redress this by describing conceptual and methodologic considerations for population health researchers interested in conducting quantitative structural intersectionality research - an intersectionality-informed research approach focused on examining how systems of power and oppression intersect to shape population health and health inequities.

Testing the Feasibility, Acceptability, and Potential Efficacy of an Innovative Digital Mental Health Care Delivery Model Designed to Increase Access to Care: Open Trial of the Digital Clinic.

Background: Mental health concerns have become increasingly prevalent; however, care remains inaccessible to many. While digital mental health interventions offer a promising solution, self-help and even coached apps have not fully addressed the challenge. There is now a growing interest in hybrid, or blended, care approaches that use apps as tools to augment, rather than to entirely guide, care.

Impact of the Mediterranean Diet on Patients With Psoriasis: Protocol for a Randomized Controlled Trial.

Background: Psoriasis is an inflammatory disease primarily treated through molecular-targeted therapies. However, emerging evidence suggests that dietary interventions may also play a role in managing inflammation associated with this condition. The Mediterranean diet (MedDiet), prevalent in southern European countries, has been widely recognized for its ability to reduce cardiovascular mortality, largely due to its anti-inflammatory properties.

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.

Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).

The Southern Brazilian Registry of Atrial Fibrillation (SBR-AF Registry): Predictors of Atrial Arrhythmia Recurrence after First-Time Catheter Ablation.

Background: Treatment of atrial fibrillation (AF) with catheter ablation (CA) has evolved significantly. However, real-world data on long-term outcomes are limited, particularly in low- and middle-income countries.

Objective: This multicenter prospective cohort of consecutive patients aimed to evaluate the safety and efficacy of first-time CA for AF in Southern Brazil from 2009 to 2024.

Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.

Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.

Correcting a pathogenic mitochondrial DNA mutation by base editing in mice.

Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.

Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection.

At this stage in the COVID-19 pandemic, most infections are "breakthrough" infections that occur in individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity in breakthrough infections. We performed single-cell transcriptomic, proteomic, and functional profiling of primary and breakthrough infections to compare immune responses from unvaccinated and vaccinated individuals during the SARS-CoV-2 Delta wave.