Functionally selective signaling and broad metabolic benefits by novel insulin receptor partial agonists.

Insulin analogs have been developed to treat diabetes with focus primarily on improving the time action profile without affecting ligand-receptor interaction or functional selectivity. As a result, inherent liabilities (e.g.

Frequency and timing of emergency department visits and hospital admissions in stented patients following common stone procedures.

Emergency department (ED) visits and hospital admissions (HA) following urologic procedures are a concern for payors, providers, and patients. We seek to quantify ED visits and HA after urologic stone procedures. This is a retrospective cohort study using claims data from the IBM MarketScan Commercial and Medicare Supplement database.

Trans-ethnic genome-wide association study of blood metabolites in the Chronic Renal Insufficiency Cohort (CRIC) study.

Metabolomics genome wide association study (GWAS) help outline the genetic contribution to human metabolism. However, studies to date have focused on relatively healthy, population-based samples of White individuals. Here, we conducted a GWAS of 537 blood metabolites measured in the Chronic Renal Insufficiency Cohort (CRIC) Study, with separate analyses in 822 White and 687 Black study participants.

Infectious Bronchitis Virus Surveillance in Broilers in California (2012-20).

Infectious bronchitis virus (IBV) causes severe economic losses among chicken flocks worldwide. Although IBV molecular surveillance has been conducted in California broilers, seasonal and spatial-temporal trends in IBV prevalence are poorly defined. The goals of this study were to evaluate seasonal and spatial-temporal trends in IBV prevalence and to determine the predominant IBV genotypes obtained over the last 8 yr from a broiler company located in the California Central Valley.

Prospective Predictors of Blood Pressure Among African American Men Living with HIV.

Little is known about the predictors of blood pressure (BP) among African American men living with HIV. We examined whether age and body mass index (BMI) are associated with higher blood pressure (BP) and whether being married and muscular endurance are associated with lower BP among African American men living with HIV. Second, we examined whether being married moderated the effects of the other predictors on BP.

Implications of a patent foramen ovale for environmental physiology and pathophysiology: do we know the 'hole' story?

The foramen ovale is an essential component of the fetal circulation contributing to oxygenation and carbon dioxide elimination that remains patent under certain circumstances in ∼30% of the healthy adult population, without major negative sequelae in most. Adults with a patent foramen ovale (PFO) have a greater tendency to develop symptoms of acute mountain sickness and high-altitude pulmonary oedema upon ascent to high altitude, and PFO presence is associated with worse cardiopulmonary function in chronic mountain sickness. This increase in altitude illness prevalence may be related to dysregulated cerebral blood flow associated with altered respiratory chemoreflex sensitivity; however, the mechanisms remain to be elucidated.

Association Between Baseline Buccal Telomere Length and Progression of Kidney Function: The Health and Retirement Study.

We aimed to evaluate associations of baseline telomere length with overall and annual change in estimated glomerular filtration rate (eGFR) and trajectory of kidney function during an 8-year follow-up. A total of 3 964 participants of the Health and Retirement Study were included. We identified 3 trajectory groups of kidney function: consistently normal (n = 1 163 or 29.

A Case of Successful Endovascular Aortic Repair of Primary Aortoenteric Fistula Without Aortic Explantation.

Purpose: The objective of this study is to report a case of a primary aortoenteric fistula successfully treated with endovascular repair without aortic explant.

Case Report: A 48-year-old man presented with a 24-hour history of hematemesis and malena. A computed tomography (CT) abdomen and pelvis demonstrated a 6 cm infrarenal aortic aneurysm with periaortic stranding and contrast enhancement within the lumen of the third part of the duodenum.

The Neuroprotective Effects of the CB2 Agonist GW842166x in the 6-OHDA Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a chronic neurodegenerative disorder associated with dopamine neuron loss and motor dysfunction. Neuroprotective agents that prevent dopamine neuron death hold great promise for slowing the disease's progression. The activation of cannabinoid (CB) receptors has shown neuroprotective effects in preclinical models of neurodegenerative disease, traumatic brain injury, and stroke, and may provide neuroprotection against PD.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

Active Rehabilitation in a Patient During and After Venovenous Extracorporeal Membrane Oxygenation With a Diagnosis of COVID-19: A Case Report.

Purpose: The coronavirus disease-2019 (COVID-19) pandemic has resulted in an influx of critically ill patients requiring mechanical ventilation, some receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO). The benefits of early mobility while undergoing ECMO have been previously documented. However, the COVID-19 pandemic has presented physical therapists with novel challenges, balancing the risk of a widespread shortage of personal protective equipment (PPE) with the benefits of early mobility for patients on ECMO.

A transient reduction in circulating corticosterone reduces object neophobia in male house sparrows.

Aversive reactions to novelty (or "neophobia") have been described in a wide variety of different animal species and can affect an individual's ability to exploit new resources and avoid potential dangers. However, despite its ecological importance, the proximate causes of neophobia are poorly understood. In this study, we tested the role of glucocorticoid hormones in neophobia in wild-caught house sparrows (Passer domesticus, n = 11 males) by giving an injection of the drug mitotane that reduced endogenous corticosterone for several days or a vehicle control, and then examined the latency to feed when the food dish was presented with or without a novel object in, on, or near the dish.

γδ Intraepithelial Lymphocytes Facilitate Pathological Epithelial Cell Shedding Via CD103-Mediated Granzyme Release.

Background & Aims: Excessive shedding of apoptotic enterocytes into the intestinal lumen is observed in inflammatory bowel disease and is correlated with disease relapse. Based on their cytolytic capacity and surveillance behavior, we investigated whether intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) are actively involved in the shedding of enterocytes into the lumen.

Methods: Intravital microscopy was performed on GFP γδ T cell reporter mice treated with intraperitoneal lipopolysaccharide (10 mg/kg) for 90 minutes to induce tumor necrosis factor-mediated apoptosis.

Metabolites Associated with Coffee Consumption and Incident Chronic Kidney Disease.

Background And Objectives: Moderate coffee consumption has been associated with lower risk of CKD; however, the exact biologic mechanisms underlying this association are unknown. Metabolomic profiling may identify metabolic pathways that explain the association between coffee and CKD. The goal of this study was to identify serum metabolites associated with coffee consumption and examine the association between these coffee-associated metabolites and incident CKD.

Chromosome-specific telomere lengths and the minimal functional telomere revealed by nanopore sequencing.

We developed a method to tag telomeres and measure telomere length by nanopore sequencing in the yeast Nanopore allows long-read sequencing through the telomere, through the subtelomere, and into unique chromosomal sequence, enabling assignment of telomere length to a specific chromosome end. We observed chromosome end-specific telomere lengths that were stable over 120 cell divisions. These stable chromosome-specific telomere lengths may be explained by slow clonal variation or may represent a new biological mechanism that maintains equilibrium unique to each chromosome end.

Clinical and Preclinical Evidence for Roles of Soluble Epoxide Hydrolase in Osteoarthritis Knee Pain.

Objective: Chronic pain due to osteoarthritis (OA) is a major clinical problem, and existing analgesics often have limited beneficial effects and/or adverse effects, necessitating the development of novel therapies. Epoxyeicosatrienoic acids (EETs) are endogenous antiinflammatory mediators, rapidly metabolized by soluble epoxide hydrolase (EH) to dihydroxyeicosatrienoic acids (DHETs). We undertook this study to assess whether soluble EH-driven metabolism of EETs to DHETs plays a critical role in chronic joint pain associated with OA and provides a new target for treatment.

Lived experiences of first-year radiation therapy students communicating with patients and radiation therapists - A qualitative review using interpretative phenomenological analysis.

Introduction: Radiation therapists must possess adaptable communication skills to manage patient-centred care and provide required technical information. Adaptive communication is also an expectation of undergraduate students to gain registration in Australia. The University Of Newcastle's Clinical Reasoning Module (CRM) prepares first-year radiation therapy students for clinical interactions.

A novel weighting method to remove bias from within-subject exposure dependency in case-crossover studies.

Background: Case-crossover studies have been widely used in various fields including pharmacoepidemiology. Vines and Farrington indicated in 2001 that when within-subject exposure dependency exists, conditional logistic regression can be biased. However, this bias has not been well studied.

Secular Trends in Cardiovascular Health in US Adults (from NHANES 2007 to 2018).

Deceleration in the decline of cardiovascular disease mortality has been observed recently in the US. We aimed to examine the recent secular trends of cardiovascular health metrics in the US general population. A total of 32,832 adults aged ≥20 years from the National Health and Nutrition Examination Surveys 2007 to 2018 were included in this analysis.

Chlamydia buteonis in birds of prey presented to California wildlife rehabilitation facilities.

Chlamydial infections, caused by a group of obligate, intracellular, gram-negative bacteria, have health implications for animals and humans. Due to their highly infectious nature and zoonotic potential, staff at wildlife rehabilitation centers should be educated on the clinical manifestations, prevalence, and risk factors associated with Chlamydia spp. infections in raptors.

Ibudilast attenuates cocaine self-administration and prime- and cue-induced reinstatement of cocaine seeking in rats.

Ibudilast is a non-selective phosphodiesterase (PDE) inhibitor and glial cell modulator which has shown great promise for the treatment of drug and alcohol use disorders in recent clinical studies. However, it is unknown whether and how ibudilast affects cocaine seeking behavior. Here we show that systemic administration of ibudilast dose-dependently reduced cocaine self-administration under fixed- and progressive-ratio reinforcement schedules in rats and shifted cocaine dose-response curves downward.

Importance of attachment to place in growing a sustainable Australian Rural Health Workforce: A rapid review.

Introduction: Personal, community, and environmental factors can influence the attraction and retention of regional, rural, and remote health workers. However, the concept of place attachment needs further attention as a factor affecting the sustainability of the rural health workforce.

Objective: The purpose of this rapid review was to explore the influence of a sense of place in attracting and retaining health professionals in rural and remote areas.