The Hexosamine Biosynthetic Pathway Links Innate Inflammation With Epithelial-Mesenchymal Plasticity in Airway Remodeling.

Disruption of the lower airway epithelial barrier plays a major role in the initiation and progression of chronic lung disease. Here, repetitive environmental insults produced by viral and allergens triggers metabolic adaptations, epithelial-mesenchymal plasticity (EMP) and airway remodeling. Epithelial plasticity disrupts epithelial barrier function, stimulates release of fibroblastic growth factors, and remodels the extracellular matrix (ECM).

Development and validation of the self-management Barriers and Supports Evaluation for working-aged adults with type 1 diabetes mellitus.

Introduction: To optimize type 1 diabetes mellitus self-management, experts recommend a person-centered approach, in which care is tailored to meet people's needs and preferences. Existing tools for tailoring type 1 diabetes mellitus education and support are limited by narrow focus, lack of strong association with meaningful outcomes like A1c, or having been developed before widespread use of modern diabetes technology. To facilitate comprehensive, effective tailoring for today's working-aged adults with type 1 diabetes mellitus, we developed and validated the Barriers and Supports Evaluation (BASES).

Association of Quantified Costal Cartilage Calcification and Long-Term Cumulative Blood Glucose Exposure: The Multi-Ethnic Study of Atherosclerosis.

Aims: Anecdotal reports have suggested increased soft tissue calcification in individuals with long-term exposures to high blood glucose. The association of costal cartilage calcification (CCC), a reliably quantifiable marker obtainable from non-contrast cardiac computed tomography (CT) with cumulative fasting blood glucose (FBG) exposure, is unknown. In this study, we aimed to determine the association between quantified CCC and cumulative glucose exposure using non-contrast coronary artery calcium (CAC) scoring computed tomography (CT) images in the Multi-Ethnic Study of Atherosclerosis (MESA).

Association Between Immune Dysfunction and COVID-19 Breakthrough Infection After SARS-CoV-2 Vaccination in the US.

Importance: Persons with immune dysfunction have a higher risk for severe COVID-19 outcomes. However, these patients were largely excluded from SARS-CoV-2 vaccine clinical trials, creating a large evidence gap.

Objective: To identify the incidence rate and incidence rate ratio (IRR) for COVID-19 breakthrough infection after SARS-CoV-2 vaccination among persons with or without immune dysfunction.

Primary care providers should prescribe aspirin to prevent cardiovascular disease based on benefit-risk ratio, not age.

Recent guidelines restricted aspirin (ASA) in primary prevention of cardiovascular disease (CVD) to patients <70 years old and more recent guidance to <60.In the most comprehensive prior meta-analysis, the Antithrombotic Trialists Collaboration reported a significant 12% reduction in CVD with similar benefit-risk ratios at older ages. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, four trials were added to an updated meta-analysis.

Region-specific distribution of transversal-axial tubule system organization underlies heterogeneity of calcium dynamics in the right atrium.

The atrial myocardium demonstrates the highly heterogeneous organization of the transversal-axial tubule system (TATS), although its anatomical distribution and region-specific impact on Ca dynamics remain unknown. Here, we developed a novel method for high-resolution confocal imaging of TATS in intact live mouse atrial myocardium and applied a custom-developed MATLAB-based computational algorithm for the automated analysis of TATS integrity. We observed a twofold higher ( < 0.

Botulism outbreak in a rural Ethiopia: a case series.

Background: Foodborne botulism, a toxin-mediated illness caused by Clostridium botulinum, is a public health emergency. Types A, B, and E C. botulinum toxins commonly cause human disease.

Collaborative design and implementation of a clinical decision support system for automated fall-risk identification and referrals in emergency departments.

Of the 3 million older adults seeking fall-related emergency care each year, nearly one-third visited the Emergency Department (ED) in the previous 6 months. ED providers have a great opportunity to refer patients for fall prevention services at these initial visits, but lack feasible tools for identifying those at highest-risk. Existing fall screening tools have been poorly adopted due to ED staff/provider burden and lack of workflow integration.

Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment.

The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments.

A hormone complex of FABP4 and nucleoside kinases regulates islet function.

The liberation of energy stores from adipocytes is critical to support survival in times of energy deficit; however, uncontrolled or chronic lipolysis associated with insulin resistance and/or insulin insufficiency disrupts metabolic homeostasis. Coupled to lipolysis is the release of a recently identified hormone, fatty-acid-binding protein 4 (FABP4). Although circulating FABP4 levels have been strongly associated with cardiometabolic diseases in both preclinical models and humans, no mechanism of action has yet been described.

The Suprasellar Meningioma Patient-Reported Outcome Survey: a disease-specific patient-reported outcome measure for resection of suprasellar meningioma.

Objective: Suprasellar meningioma resection via either the transcranial approach (TCA) or the endoscopic endonasal approach (EEA) is an area of controversy and active evaluation. Skull base surgeons increasingly consider patient-reported outcomes (PROs) when choosing an approach. No PRO measure currently exists to assess quality of life for suprasellar meningiomas.

Factors Associated with Self-Reported Dysphagia in Older Adults Receiving Meal Support.

Objectives: Dysphagia is common in older adults. However, there are no current estimates of dysphagia in community-dwelling older adults those receiving meal support. It is unknown whether dysphagia is associated with other measures of physical function (activities of daily living [ADL] ability or nutrition status).

New Approaches to Cardiovascular Disease and Its Management in Kidney Transplant Recipients.

Cardiovascular events, including ischemic heart disease, heart failure, and arrhythmia, are common complications after kidney transplantation and continue to be leading causes of graft loss. Kidney transplant recipients have both traditional and transplant-specific risk factors for cardiovascular disease. In the general population, modification of cardiovascular risk factors is the best strategy to reduce cardiovascular events; however, studies evaluating the impact of risk modification strategies on cardiovascular outcomes among kidney transplant recipients are limited.

Using electronic health record's data to assess daily dose of opioids prescribed for outpatients with chronic non-cancer pain.

This research intended to examine electronic health record (EHR) based methods for automated estimation of morphine equivalent daily dose (MEDD) of prescribed opioids in primary care research and practice. The study leveraged the health system's audit of adults treated with long-term opioids for chronic non-cancer pain to compare two EHR-based automated MEDD calculation methods: RxSignature (active prescriptions' signature information) and RxQuantity (quantity dispensed for prescriptions issued within the past 90 days). Prescribed opioid EHR data were extracted from the target population at a large US academic health system in a 2-year assessment period.

Epilepsy Syndromes: Current Classifications and Future Directions.

This review describes the clinical presentations and treatment options for commonly recognized epilepsy syndromes in the pediatric age group, based on the 2017 International League Against Epilepsy classification. Structural epilepsies that are amenable to surgical intervention are discussed. Lastly, emerging technologies are reviewed that are expanding our knowledge of underlying epilepsy pathologies and will guide future syndromic classification systems including genetic testing and tissue repositories.

ARMADA: Assessing reliable measurement in Alzheimer's disease and cognitive aging project methods.

Introduction: Early detection of cognitive decline in older adults is a public health priority. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA), a multisite study, is validating cognition, emotion, motor, and sensory modules of the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in the aging spectrum from cognitively normal to dementia of the Alzheimer's type (DAT).

Methods: Participants 65 to 85 years old, in demographic groups racially proportional to the general US population, are recruited in one of three groups to validate the NIHTB: cognitively normal, amnestic mild cognitive impairment (aMCI), or mild DAT.

Sebelipase alfa in children and adults with lysosomal acid lipase deficiency: Final results of the ARISE study.

Background & Aims: Children and adults with lysosomal acid lipase deficiency (LAL-D) experience cirrhosis and dyslipidemia from lysosomal accumulation of cholesteryl esters and triglycerides. Sebelipase alfa enzyme replacement therapy is indicated for individuals with LAL-D. We report final results from the phase III randomized ARISE study of sebelipase alfa in children aged ≥4 years and adults with LAL-D.

Bromodomain Containing Protein 4 (BRD4) Regulates Expression of its Interacting Coactivators in the Innate Response to Respiratory Syncytial Virus.

Bromodomain-containing protein 4 plays a central role in coordinating the complex epigenetic component of the innate immune response. Previous studies implicated BRD4 as a component of a chromatin-modifying complex that is dynamically recruited to a network of protective cytokines by binding activated transcription factors, polymerases, and histones to trigger their rapid expression via transcriptional elongation. Our previous study extended our understanding of the airway epithelial BRD4 interactome by identifying over 100 functionally important coactivators and transcription factors, whose association is induced by respiratory syncytial virus (RSV) infection.

Congenital musculoskeletal anomalies - key radiographic findings.

Although radiographs are generally performed in the neonatal period to evaluate for causes of respiratory distress or to evaluate line placement, close attention to the osseous structures can provide important clues to an underlying diagnosis. Although segmentation anomalies can be random, they are frequently associated with more complex entities such as VACTERL association. A butterfly vertebral body can hint at a possible diagnosis of Alagille syndrome even before jaundice develops in an infant with a murmur.

Biogeography of Bacterial Communities and Specialized Metabolism in Human Aerodigestive Tract Microbiomes.

The aerodigestive tract (ADT) is the primary portal through which pathogens and other invading microbes enter the body. As the direct interface with the environment, we hypothesize that the ADT microbiota possess biosynthetic gene clusters (BGCs) for antibiotics and other specialized metabolites to compete with both endogenous and exogenous microbes. From 1,214 bacterial genomes, representing 136 genera and 387 species that colonize the ADT, we identified 3,895 BGCs.

The Natural Swallow: Factors Affecting Subject Choice of Bolus Volume and Pharyngeal Swallow Parameters in a Self-selected Swallow.

Predetermined volumes are used extensively throughout clinical assessment of swallowing physiology, but bolus volumes selected by an individual in their natural swallow can vary greatly from those used in structured assessment. This study aims to identify factors influencing self-selected volume and how the mechanics of self-selected volume swallows differ from predetermined volume swallows. We used pharyngeal high-resolution manometry (HRM) with simultaneous videofluoroscopy to measure swallowing pressures in the velopharynx, hypopharynx, and upper esophageal sphincter (UES).

In vivo staging of regional amyloid progression in healthy middle-aged to older people at risk of Alzheimer's disease.

Background: We investigated regional amyloid staging characteristics in C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled in the Wisconsin Registry for Alzheimer's Prevention.

Methods: We analyzed partial volume effect-corrected C-PiB-PET distribution volume ratio maps from 220 participants (mean age = 61.4 years, range 46.