Aging Disparities in Ostomy Surgery.

Introduction: Little is known about the association between age and fecal ostomy surgery trends over time. We aim to 1) determine the rate of fecal ostomy operations over time and 2) compare rates of colostomy formation between patients older and younger than 65 y.

Materials And Methods: Retrospective multi-institutional cohort study of patients ≥18 y who underwent colorectal resection between 2003 and 2014 using the Nationwide Inpatient Sample database.

Pharmacokinetic modeling of prenatal vitamin D exposure and the impact on offspring asthma and pulmonary function.

Gestational 25-hydroxyvitamin D (25[OH]D) is important in fetal lung development and may influence offspring respiratory outcomes, making accurate exposure assessment essential to understand clinical associations. Therefore, we used the combined data from two large RCTs investigating prenatal vitamin D supplementation, which included early and late prenatal 25(OH)D measurements, to refine a population pharmacokinetic model of vitamin D-25(OH)D and estimate individual area under the curve (AUC) Z-scores. The primary outcome was physician-diagnosed offspring asthma/wheezing at ages 3 and 6 years, and lung function, as a secondary outcome, was evaluated by spirometry at the ages 6 and 8 years.

The effect of conflicting versus consistent messaging on older women's support for breast cancer screening cessation.

Objective: Breast cancer over-screening is common in older women. Messaging about breast cancer screening cessation may reduce over-screening but the broader informational environment often emphasizes screening continuation. We aimed to examine the effect of receiving consistent messages about breast cancer screening cessation versus conflicting messages (i.

Designer Organs: Ethical Genetic Modifications in the Era of Machine Perfusion.

Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant.

Convening Hispanic/Latino Caregiving Advisors for Inclusive Research in Dementia Palliative Care.

Dementia clinical trials often fail to include diverse and historically minoritized groups. We sought to adapt the Alzheimer's Disease and Related Dementias-Palliative Care (ADRD-PC) clinical trial to improve enrollment and address the cultural needs of people with late-stage ADRD who identify as Hispanic or Latino and their family caregivers. Bilingual, bicultural research team members adapted study materials and processes using the Cultural Adaptation Process Model.

Pre-pandemic leukocyte count is associated with severity of post-acute sequelae of SARS-CoV-2 infection among older women in the Women's Health Initiative.

Objective: Although dysregulated inflammation has been postulated as a biological mechanism associated with post-acute sequelae of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection (PASC) and shown to be a correlate and an outcome of PASC, it is unclear whether inflammatory markers can prospectively predict PASC risk. We examined the association of leukocyte count and high-sensitivity C-reactive protein (hsCRP) concentrations, measured ~25 years prior to the coronavirus disease 2019 (COVID-19) pandemic, with PASC, PASC severity, and PASC-associated cognitive outcomes at follow-up among postmenopausal women.

Methods: Using biomarker data from blood specimens collected during pre-pandemic enrollment (1993-1998) and data on 1,237 Women's Health Initiative participants who completed a COVID-19 survey between June 2021 and February 2022, we constructed multivariable regression models that controlled for pertinent characteristics.

Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing.

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system.

AMH protects the ovary from doxorubicin by regulating cell fate and the response to DNA damage.

Anti-Müllerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, DOX toxicity and AMH rescue mechanisms in the ovary have remained unclear. Herein, we characterize the consequences of these treatments in ovarian cell types using scRNAseq.

Assessing Traumatic Brain Injury in Refugees: Feasibility, Usability, and Prevalence Insights From a US-Based Clinical Sample.

Objective: This study assessed (1) the feasibility and usability of traumatic brain injury (TBI) assessment using the Ohio State University TBI Identification Method (OSU-TBI-ID) in a sample of English and Spanish-speaking refugees and asylum seekers (hereafter refugees), and (2) the prevalence and characteristics of TBI in this population.

Setting And Participants: Refugees seeking care from Massachusetts General Hospital (MGH) Asylum Clinic, the MGH Chelsea HealthCare Center, and other asylum programs in the Greater Boston Area.

Design And Main Measures: Bilingual clinical research coordinators screened 158 English and Spanish-speaking refugees using the OSU-TBI-ID.

Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials.

Association of Frailty Index at 66 Years of Age with Health Care Costs and Utilization Over 10 Years in Korea: Retrospective Cohort Study.

Background: The long-term economic impact of frailty measured at the beginning of elderhood is unknown.

Objective: The objective of our study was to examine the association between an individual's frailty index at 66 years of age and their health care costs and utilization over 10 years.

Methods: This retrospective cohort study included 215,887 Koreans who participated in the National Screening Program for Transitional Ages at 66 years of age between 2007-2009.

The Neurodiversity Framework in Medicine: On the Spectrum.

The term "neurodiversity" refers to the natural heterogeneity in human neurological functioning, which includes neurodevelopmental differences and other mental health conditions (e.g., autism spectrum disorder [ASD], attention-deficit hyperactivity disorder [ADHD], dyslexia, bipolar disorder, schizophrenia, and depression).

Central arterial stiffness in young adults with perinatal HIV exposure & infection.

Objective: To compare arterial stiffness between young adults with perinatally acquired HIV (YAPHIV) and young adults perinatally HIV exposed but uninfected (YAPHEU).

Design: Cross-sectional analysis of pulse wave velocity (PWV) measures among participants with echocardiography in the PHACS Cardiac Toxicity Substudy.

Methods: A total of 150 participants (95 YAPHIV, 55 YAPHEU, mean 23.

Net Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: The net clinical effect of early vs later direct oral anticoagulant (DOAC) initiation after atrial fibrillation-associated ischemic stroke is unclear.

Objective: To investigate whether early DOAC treatment is associated with a net clinical benefit (NCB).

Design, Setting, And Participants: This was a post hoc analysis of the Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation (ELAN) open-label randomized clinical trial conducted across 103 sites in 15 countries in Europe, the Middle East, and Asia between November 6, 2017, and September 12, 2022, with a 90-day follow-up.

Temperature Exposure and Psychiatric Symptoms in Adolescents From 2 European Birth Cohorts.

Importance: Climate change can adversely affect mental health, but the association of ambient temperature with psychiatric symptoms remains poorly understood.

Objective: To assess the association of ambient temperature exposure with internalizing, externalizing, and attention problems in adolescents from 2 population-based birth cohorts in Europe.

Design, Setting, And Participants: This cohort study analyzed data from the Dutch Generation R Study and the Spanish INMA (Infancia y Medio Ambiente) Project.

Safety and Efficacy of Lotilaner Ophthalmic Solution (0.25%) in Treating Demodex Blepharitis: Pooled Analysis of Two Pivotal Trials.

Introduction: Lotilaner ophthalmic solution (0.25%) is the first United States Food and Drug Administration (US FDA)-approved drug for treating Demodex blepharitis. In pivotal trials, it was found to be well tolerated and demonstrated a significant reduction in collarettes and mite density after a 6-week treatment regimen.

Early transcriptional effects of inflammatory cytokines reveal highly redundant cytokine networks.

Inflammatory cytokines are fundamental mediators of the organismal response to injury, infection, or other harmful stimuli. To elucidate the early and mostly direct transcriptional signatures of inflammatory cytokines, we profiled all immunologic cell types by RNAseq after systemic exposure to IL1β, IL6, and TNFα. Our results revealed a significant overlap in the responses, with broad divergence between myeloid and lymphoid cells, but with very few cell-type-specific responses.

The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis.

Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on how meningeal immunocytes guard brain homeostasis in healthy individuals remains limited. This study highlights the heterogeneous, polyfunctional regulatory T cell (T) compartment in the meninges.

Development of Potent and Selective CK1α Molecular Glue Degraders.

Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation.

Policy Recommendations to Support Equitable Access to Long-Acting Injectables for Human Immunodeficiency Virus Prevention and Treatment: A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association.

Long-acting injectables (LAIs) for HIV prevention and treatment could dramatically improve health outcomes and health equity for people with HIV and those who could benefit from pre-exposure prophylaxis. Despite widespread acceptability and demand by providers and potential users of LAIs, implementation has been extremely limited since the introduction of cabotegravir/rilpivirine, the first LAI for HIV treatment, in January 2021, and long-acting cabotegravir, the first LAI for HIV prevention, in December 2021. We report results of a provider survey, conducted by the HIV Medicine Association, which identified LAI implementation barriers related to health insurance processes, staffing and administrative support, drug costs and acquisition, and access for individuals who are uninsured.

Frequently arising ESX-1-associated phase variants influence fitness in the presence of host and antibiotic pressures.

Unlabelled: (Mtb) exhibits an impressive ability to adapt to rapidly changing environments, despite its genome's apparent stability. Recently, phase variation through indel formation in homopolymeric tracts (HT) has emerged as a potentially important mechanism promoting adaptation in Mtb. This study examines the impact of common phase variants associated with the ESX-1 type VII secretion system, focusing on a highly variable HT upstream of the ESX-1 regulatory factor, .

Recovery support services as part of the continuum of care for alcohol or drug use disorders.

Background: The definition of 'recovery' has evolved beyond merely control of problem substance use to include other aspects of health and wellbeing (known as 'recovery capital') which are important to prevent relapse to problematic alcohol or other drug (AOD) use. Developing a Recovery Oriented System of Care (ROSC) requires consideration of interventions or services (Recovery Support Services, RSS) designed to build recovery capital which are often delivered alongside established treatment structures. Lived experience and its application to the process of engaging people, changing behaviour and relapse prevention is an essential part of these services.