Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise.

In the Greenlandic Inuit population, 4% are homozygous carriers of a genetic nonsense TBC1D4 p.Arg684Ter variant leading to loss of the muscle-specific isoform of TBC1D4 and an approximately tenfold increased risk of type 2 diabetes. Here we show the metabolic consequences of this variant in four female and four male homozygous carriers and matched controls.

Video versus audio telehealth in safety net clinic patients: Changes by rurality and time.

Background: Understanding the mix of video versus audio telehealth modality is critical to informing care for low-income safety net clinic patients. Our study examined whether telehealth modality and continued use of telehealth varied by rurality and whether that changed over time.

Methods: Encounters from adults in the OCHIN national network of primary care safety net clinics were identified by encounter type (in-person vs telehealth) and telehealth modality (video vs audio) from 4/1/2021 to 3/31/2023.

Rural-urban differences in emergency medical services bypass routing of stroke in North Carolina.

Purpose: Acute stroke is a serious, time-sensitive condition requiring immediate medical attention. Emergency medical services (EMS) routing and direct transport of acute stroke patients to stroke centers improves timely access to care. This study aimed to describe EMS stroke routing and transports by rurality in North Carolina (NC).

Trends in and factors associated with family physician-performed screening colonoscopies in the United States: 2016-2021.

Purpose: Family physician (FP)-performed screening colonoscopies can serve as 1 strategy in the multifaceted strategy necessary to improve national colorectal cancer screening rates, particularly in rural areas where specialist models can fail. However, little research exists on the performance of this strategy in the real world. In this study, we evaluated trends in and factors associated with FP-performed screening colonoscopies in the United States between 2016 and 2021.

Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.

Background: Pulmonary hypertension (PH) is a major complication linked to adverse outcomes in heart failure with preserved ejection fraction (HFpEF), yet no specific therapies exist for PH associated with HFpEF (PH-HFpEF). We have recently reported on the role of skeletal muscle SIRT3 (sirtuin-3) in modulation of PH-HFpEF, suggesting a novel endocrine signaling pathway for skeletal muscle modulation of pulmonary vascular remodeling.

Methods: Using skeletal muscle-specific knockout mice () and mass spectrometry-based comparative secretome analysis, we attempted to define the processes by which skeletal muscle SIRT3 defects affect pulmonary vascular health in PH-HFpEF.

Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.

Recent studies suggest that human-associated bacteria interact with host-produced steroids, but the mechanisms and physiological impact of such interactions remain unclear. Here, we show that the human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert abundant biliary corticoids into progestins through 21-dehydroxylation, thereby transforming a class of immuno- and metabo-regulatory steroids into a class of sex hormones and neurosteroids. Using comparative genomics, homologous expression, and heterologous expression, we identify a bacterial gene cluster that performs 21-dehydroxylation.

EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma.

Estimating progression-free survival (PFS) and overall survival superiority during clinical trials of multiple myeloma (MM) has become increasingly challenging as novel therapeutics have improved patient outcomes. Thus, it is imperative to identify earlier end point surrogates that are predictive of long-term clinical benefit. Minimal residual disease (MRD)-negativity is a common intermediate end point that has shown prognostic value for clinical benefit in MM.

Immunogenicity phase II study evaluating booster capacity of nonadjuvanted AKS-452 SARS-Cov-2 RBD Fc vaccine.

AKS-452, a subunit vaccine comprising an Fc fusion of the ancestral wild-type (WT) SARS-CoV-2 virus spike protein receptor binding domain (SP/RBD), was evaluated without adjuvant in a single cohort, non-randomized, open-labelled phase II study (NCT05124483) at a single site in The Netherlands for safety and immunogenicity. A single 90 µg subcutaneous booster dose of AKS-452 was administered to 71 adults previously primed with a registered mRNA- or adenovirus-based vaccine and evaluated for 273 days. All AEs were mild and no SAEs were attributable to AKS-452.

The impact of rural general hospital closures on communities-A systematic review of the literature.

Purpose: To compile the literature on the effects of rural hospital closures on the community and summarize the evidence, specifically the health and economic impacts, and identify gaps for future research.

Methods: A systematic review of the relevant peer-reviewed literature, published from January 2005 through December 2021, included in the EMBASE, CINAHL, PubMed, EconLit, and Business Source Complete databases, as well as "gray" literature published during the same time period. A total of 21 articles were identified for inclusion.

The role of comorbidities, medications, and social determinants of health in understanding urban-rural outcome differences among patients with heart failure.

Purpose: There is now a 20% disparity in all-cause, excess deaths between urban and rural areas, much of which is driven by disparities in cardiovascular death. We sought to explain the sources of these disparities for Medicare beneficiaries with heart failure with reduced ejection fraction (HFrEF).

Methods: Using a sample of Medicare Parts A, B, and D, we created a cohort of 389,528 fee-for-service beneficiaries with at least 1 heart failure hospitalization from 2008 to 2017.

Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study.

Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT).

Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID).

Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers.

Cingulate dynamics track depression recovery with deep brain stimulation.

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD). However, achieving stable recovery is unpredictable, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention.

Safety, Virology, Pharmacokinetics, and Clinical Experience of High-Dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-Label Clinical Trial.

Background: Five hundred milligrams of intravenous (IV) sotrovimab has been shown to be well tolerated and efficacious against pre-Omicron strains in treating patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk for disease progression.

Methods: This was an open-label, single-arm substudy of phase 3 COMET-TAIL (NCT04913675) assessing the safety and tolerability of a 2000 mg IV dose of sotrovimab. Symptomatic patients (aged ≥18 years) with COVID-19 at high risk for progression were enrolled from June 30 through July 11, 2022, when Omicron BA.

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis.

Objectives: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF).

Methods: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments.

Medication treatment for opioid use disorder among rural primary care patients.

Purpose: To investigate the prevalence of opioid use disorder (OUD) and medication treatment for OUD (MOUD) receipt in rural primary care settings and identify characteristics associated with MOUD among patients with OUD.

Methods: Secondary analyses based on electronic health records of all adult patients who visited 1 of the 6 rural primary care clinic sites from October 2019 to January 2021. Mixed effects logistic regression was conducted to assess MOUD receipt (Y/N) in relation to patient characteristics (eg, demographics, other substance use disorders [SUDs], mental health disorders, and chronic pain) and the number of MOUD prescribers per clinic.

Assessment of Codispensing Patterns of Mirabegron and Prespecified CYP2D6 Substrates in Patients with Overactive Bladder.

Background: Patients with overactive bladder (OAB) experience sudden, intense urges to urinate, which may include urge urinary incontinence and nocturia. Pharmacotherapy includes β-adrenergic receptor agonists such as mirabegron; however, mirabegron contains a label warning for cytochrome P450 (CYP) 2D6 inhibition, making coadministration with CYP2D6 substrates require monitoring and dose adjustment to avoid unintended increases in substrate concentration.

Objective: To understand the codispensing patterns of mirabegron among patients using ten predefined CYP2D6 substrates with and before mirabegron dispensing.

Care coordination between rural primary care and telemedicine to expand medication treatment for opioid use disorder: Results from a single-arm, multisite feasibility study.

Purpose: The use of telemedicine (TM) has accelerated in recent years, yet research on the implementation and effectiveness of TM-delivered medication treatment for opioid use disorder (MOUD) has been limited. This study investigated the feasibility of implementing a care coordination model involving MOUD delivered via an external TM provider for the purpose of expanding access to MOUD for patients in rural settings.

Methods: The study tested a care coordination model in 6 rural primary care sites by establishing referral and coordination between the clinic and a TM company for MOUD.

Rural communities face more than an opioid crisis: Reimagining funding assistance to address polysubstance use, associated health problems, and limited rural service capacity.

Purpose: Rural communities in the United States face unique challenges related to the opioid epidemic. This paper explores the substances and substance-related health problems that pose the greatest concern to rural communities that received funding to address the opioid epidemic and examines their reported capacity to address these challenges.

Methods: This paper analyzed data collected as part of quarterly progress reporting from multisector consortiums across 2 cohorts of grantees funded to reduce the morbidity and mortality of opioids.

Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature.

Nitric-oxide-stimulating dietary supplements are widely available and marketed to strength athletes and weightlifters seeking to increase muscle performance and augment training adaptations. These supplements contain ingredients classified as nitric oxide (NO) precursors (i.e.

Reinfection with SARS-CoV-2 and Waning Humoral Immunity: A Case Report.

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G.

Intratumoral oncolytic virus V937 plus ipilimumab in patients with advanced melanoma: the phase 1b MITCI study.

Background: Intratumoral administration of V937, a bioselected, genetically unmodified coxsackievirus A21, has previously demonstrated antitumor activity in patients with advanced melanoma as monotherapy and in combination with the programmed cell death 1 (PD-1) antibody pembrolizumab. We report results from an open-label, single-arm, phase 1b study (NCT02307149) evaluating V937 plus the cytotoxic T-lymphocyte antigen 4 inhibitor ipilimumab in patients with advanced melanoma.

Methods: Adult patients (aged ≥18 years) with histologically confirmed metastatic or unresectable stage IIIB/C or IV melanoma received intratumoral V937 on days 1, 3, 5, 8, and 22 and every 3 weeks (Q3W) thereafter for up to 19 sets of injections plus intravenous ipilimumab 3 mg/kg Q3W administered for four doses starting on day 22.