Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Respiratory syncytial virus vaccine effectiveness among US veterans, September, 2023 to March, 2024: a target trial emulation study.

Background: New respiratory syncytial virus (RSV) vaccines have been approved in the USA for the prevention of RSV-associated lower respiratory tract disease in adults aged 60 years and older. Information on the real-world effectiveness of these vaccines is needed.

Methods: We used electronic health records in the Veterans Health Administration to emulate a target trial comparing a single dose of a recombinant stabilised prefusion F protein RSV vaccine versus no vaccination among veterans aged 60 years and older.

Comparison of Temporal Artery and Rectal Temperature Measurement During Cooling and Rewarming in Neonates Treated for Hypoxic Ischemic Encephalopathy.

Background: Finding an accurate and simple method of thermometry in the neonatal intensive care unit is important. The temporal artery thermometer (TAT) has been recommended for all ages by the manufacturer; however, there is insufficient evidence for the use of TAT in infants, especially to detect hypothermia.

Purpose: To assess the accuracy of the TAT in hypothermic neonates in comparison to a rectal thermometer.

Arterial stiffness mediates insulin resistance-related risk of atherosclerotic cardiovascular disease: a real-life, prospective cohort study.

Background: The precise pathways connecting insulin resistance (IR) to atherosclerotic cardiovascular disease (ASCVD) remain undefined. The present study aimed to examine the mediating role of arterial stiffness in the association between IR and ASCVD, providing epidemiology insights into the potential mechanisms driving IR to incident ASCVD.

Methods: A total of 59,777 participants from the Kailuan Study Arterial Stiffness Subcohort who were free of ASCVD at baseline were enrolled in the present study.

Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence.

Background: Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear.

Methods: We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated.

Influences of gonad developmental stage on ovary selenium concentrations in fish-implications for ovary selenium monitoring.

Monitoring selenium (Se) concentrations in fish ovaries is an important tool for evaluating the ecological risk posed by Se in aquatic systems. Most guidance recommends sampling fish ovaries as closely as possible to when fish spawn on the premise that Se is mobilized from the liver to the ovary during vitellogenesis, and therefore, sampling ovaries during the early phases of oocyte maturation may underestimate egg Se concentrations at the time of spawning. In this study, we evaluated ovary Se data from two species with synchronous oocyte development (Ptychocheilus oregonensis and Prosopium williamsoni), one species with asynchronous oocyte development (Richardsonius balteatus), and one where the mode of development is unclear (Mylocheilus caurinus).

Ceftobiprole: A therapeutic update.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

A Pilot Trial of Nicotinamide Riboside and Coenzyme Q10 on Inflammation and Oxidative Stress in Chronic Kidney Disease.

Background: Mitochondria-driven oxidative/redox stress and inflammation play a major role in chronic kidney disease (CKD) pathophysiology. Compounds targeting mitochondrial metabolism may improve mitochondrial function, inflammation, and redox stress; however, there is limited evidence of their efficacy in CKD.

Methods: We conducted a pilot randomized, double-blind, placebo-controlled crossover trial comparing the effects of 1200 mg/day of coenzyme Q10 (CoQ10) or 1000 mg/day of nicotinamide riboside (NR) supplementation to placebo in 25 people with moderate-to-severe CKD (estimated glomerular filtration rate [eGFR] <60mL/min/1.

Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.

Many proteins form paralogous multimers-molecular complexes in which evolutionarily related proteins are arranged into specific quaternary structures. Little is known about the mechanisms by which they acquired their stoichiometry (the number of total subunits in the complex) and heterospecificity (the preference of subunits for their paralogs rather than other copies of the same protein). Here, we use ancestral protein reconstruction and biochemical experiments to study historical increases in stoichiometry and specificity during the evolution of vertebrate hemoglobin (Hb), an αβ heterotetramer that evolved from a homodimeric ancestor after a gene duplication.

Outcomes of chronic limb-threatening ischemia revascularization in patients with chronic kidney disease in the BEST-CLI trial.

Background: Chronic limb-threatening ischemia (CLTI) in patients with chronic kidney disease (CKD) has a high risk of poor outcomes. We aimed to compare the outcomes of lower extremity revascularization in patients with CLTI stratified by CKD severity in patients enrolled in the prospective, randomized Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial.

Methods: The BEST-CLI trial dataset was queried to categorize patients into three groups according to CKD stage.

Atraumatic Rhegmatogenous Retinal Detachment: Epidemiology and Association with Refractive Error in U.S. Armed Forces Service Members.

Purpose: To evaluate the incidence, refractive error (RE) association, and distribution of atraumatic rhegmatogenous retinal detachment (RRD) in U.S. military service members (SMs).

Defining a novel DYRK1A-gp130/IL-6R-pSTAT axis that regulates Th17 differentiation.

Dysregulated differentiation of naïve CD4+ T cells into T helper 17 (Th17) cells is likely a key factor predisposing to many autoimmune diseases. Therefore, better understanding how Th17 differentiation is regulated is essential to identify novel therapeutic targets and strategies to identify individuals at high risk of developing autoimmunity. Here, we extend our prior work using chemical inhibitors to provide mechanistic insight into a novel regulator of Th17 differentiation, the kinase dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A).

A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator.

Background: Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.

Methods: Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk.

Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity.

For many genetic disorders, there are no specific metabolic biomarkers nor analytical methods suitable for newborn population screening, even where highly effective preemptive treatments are available. The direct measurement of signature peptides as a surrogate marker for the protein in dried blood spots (DBSs) has been shown to successfully identify patients with Wilson Disease (WD) and three life-threatening inborn errors of immunity, X-linked agammaglobulinemia (XLA), Wiskott-Aldrich syndrome (WAS), and adenosine deaminase deficiency (ADAD). A novel proteomic-based multiplex assay to detect these four conditions from DBS using high-throughput LC-MS/MS was developed and validated.

Interest in Injectable and Oral PrEP for HIV Prevention Among Women and Men Who Inject Drugs.

Background: People who inject drugs (PWID) are at increased risk for human immunodeficiency virus (HIV). Women who inject are a particularly vulnerable group. Preexposure prophylaxis (PrEP) is effective, but access and uptake has been limited.

Gender differences in early posttraumatic stress disorder symptoms: a network analysis.

Despite known gender/sex differences in the prevalence of posttraumatic stress disorder (PTSD), potential differences in the associations among PTSD symptoms between men and women in the early post-trauma period are not well-characterized. This study utilized network analysis to assess potential differences in the associations among PTSD symptom clusters between men and women during the early post-trauma period. We included  = 475 participants (57.

Practical and economic challenges of implementing group auricular acupuncture treatment for chronic pain in primary care.

Background: Although growing numbers of patients seek acupuncture for pain management, few acupuncturists with insurance credentialing work in the conventional medical settings. This has resulted in increasing frustration among patients wishing to receive acupuncture in primary care settings as part of their insurance benefits.

Methods: A course of eight weekly sessions of group auricular acupuncture (AA) for chronic musculoskeletal pain was implemented in a US primary care clinic and billed to insurance.

Genomic sequencing in diverse and underserved pediatric populations: parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

Purpose: Limited evidence evaluates parents' perceptions of their child's clinical genomic sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research (CSER) consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.

Methods: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure.

Placental Hypoxia-Induced Ferroptosis Drives Vascular Damage in Preeclampsia.

Background: Iron is an essential micronutrient for cell survival and growth; however, excess of this metal drives ferroptosis. Although maternal iron imbalance and placental hypoxia are independent contributors to the pathogenesis of preeclampsia, a hypertensive disorder of pregnancy, the mechanisms by which their interaction impinge on maternal and placental health remain elusive.

Methods: We used placentae from normotensive and preeclampsia pregnancy cohorts, human H9 embryonic stem cells differentiated into cytotrophoblast-like cells, and placenta-specific preeclamptic mice.

Classifying Race in Out-of-Hospital Cardiac Arrest and Potential Disparities: A Retrospective Cohort Study.

Background: Although racial disparities have been described in resuscitation, little is known about potential bias in race classification of out-of-hospital cardiac arrest (OHCA).

Methods: We conducted a retrospective cohort study of adults treated by emergency medical services (EMS) for nontraumatic OHCA in King County, WA between January 1, 2018, and December 31, 2021. We assessed agreement using κ and evaluated patterns of missingness between EMS-assessed race versus comprehensive race classification from hospital and death records.