Oxidative stress suppresses internal carotid artery dilation to hypercapnia in healthy older adults.

: Cerebrovascular disease and dementia risk increases with age and lifetime risk is greater in women. Cerebrovascular dysfunction likely precedes cerebrovascular disease and dementia but the mechanisms are incompletely understood. We hypothesized that oxidative stress mediates cerebrovascular dysfunction with human aging.

Emergence of antibiotic-specific phenotypes during prolonged treatment of mice.

A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiology of (), which may enable the pathogen to withstand treatment. While antibiotic-treated has been evaluated in experiments it is unclear if and how long-term treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affects physiologic processes differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the transcriptome in the BALB/c high-dose aerosol infection mouse model following 4 weeks of treatment with three sterilizing and three non-sterilizing antibiotics.

Prevalence of co-occurring conditions among youths receiving treatment with primary anxiety, ADHD, or depressive disorder diagnoses.

Introduction: Anxiety disorders, depressive disorders, and attention-deficit/hyperactivity disorder (ADHD) are some of the most common conditions that youths (<18 years old) receive mental health treatment for. These conditions are associated with high-risk substance use or substance use disorders (SUDs). This study sought to identify the proportion of youths (<18 years old) with anxiety disorders, depressive disorders, or ADHD as a primary diagnosis in community mental health centers (CMHCs) having co-occurring high-risk substance use or a SUD.

New Frontiers: Umbilical Cord Mesenchymal Stem Cells Uncover Developmental Roots and Biological Underpinnings of Obesity Susceptibility.

Purpose Of Review: To review evidence supporting human umbilical cord mesenchymal stem cells (UC-MSC) as an innovative model system advancing obesity precision medicine.

Recent Findings: Obesity prevalence is increasing rapidly and exposures during fetal development can impact individual susceptibility to obesity. UC-MSCs exhibit heterogeneous phenotypes associated with maternal exposures and predictive of child cardiometabolic outcomes.

Long-term exposure to ambient air pollution and epigenetic age acceleration in children.

Long-term exposure to ambient air pollution has been associated with epigenetic age acceleration (EAA) in adults, but its impact on children remains less understood. This study analyzed data from 457 children (mean age: 7.9 years) in the Project Viva cohort (2007-2010, eastern Massachusetts, USA).

Engineering vaginal film platform for mucoadhesion and sustained drug release for HIV-1 prevention.

User adherence contributes to the effectiveness of topical pre-exposure prophylactic products designed to protect against human immunodeficiency virus type 1 (HIV-1) infection. Long-acting approaches that do not require daily or coitally-dependent use could potentially improve user adherence. This study aims to develop a long-acting vaginal film to deliver an integrase inhibitor, MK-2048, for prevention of HIV-1 infection.

Pharmacokinetics and safety of bictegravir in pregnant and postpartum persons with HIV and their infants.

Background: Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.

Setting: Nonrandomized, open-label, multi-center phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.

Methods: Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the 2nd and 3rd trimesters and postpartum was performed.

β3 accelerates microtubule plus end maturation through a divergent lateral interface.

β-tubulin isotypes exhibit similar sequences but different activities, suggesting that limited sequence divergence is functionally important. We investigated this hypothesis for TUBB3/β3, a β-tubulin linked to aggressive cancers and chemoresistance in humans. We created mutant yeast strains with β-tubulin alleles that mimic variant residues in β3 and find that residues at the lateral interface are sufficient to alter microtubule dynamics and response to microtubule targeting agents.

General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

Intracellular tenofovir-diphosphate concentrations in HIV pre-exposure prophylaxis users who underwent bariatric surgery.

Objective: To measure concentrations of tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) among individuals taking tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) or tenofovir alafenamide plus emtricitabine (TAF/FTC) who were scheduled to undergo or had already undergone bariatric surgery.

Methods: We enrolled pre-exposure prophylaxis (PrEP) users attending clinics in Toronto or Ottawa who were undergoing or had undergone bariatric surgery. After participants completed a minimum of 7 days of consecutive PrEP dosing, we collected DBS samples immediately before they administered their next daily dose of PrEP.

Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC.

Objective: Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy.

Background: Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-angiogenic, and has been implicated in the pathogenesis of peripartum cardiomyopathy (PPCM).

Methods: In 99 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, CD levels were assessed by ELISA from serum obtained at study entry.

Chronic Health Conditions in the Workplace: Work Stressors and Supportive Supervision, Work Design, and Programs.

A large and growing number of workers are managing chronic physical and mental health conditions while working, necessitating attention from both researchers and leaders and practitioners in organizations. Much of the current discourse around research and practice in this area is focused on prevention of chronic disease and rehabilitation of disability to help workers return to work. Less commonly attended to are workplace factors that can support the quality of working life and the longevity of working life for workers with chronic health conditions.

Recommendations for Specialty Palliative APRN Graduate Education.

Background: Advanced practice registered nurses (APRNs) are essential to care for the growing number of individuals with advanced illness given the shortage of palliative care clinicians.

Problem: Graduate education for specialty practice palliative APRNs lacks consistency in structure, content, and standardization of specialty palliative APRN education.

Approach: A workgroup of expert palliative APRNs and graduate faculty conducted focused discussions and a literature review to develop consensus recommendations based on national palliative APRN competencies and aligned with the 8 core concepts of the AACN Essentials.

Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden.

Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet.

Longitudinal Trends in Physical Activity Among Older Adults With and Without HIV in Uganda.

Introduction: Physical Activity (PA) and its links to frailty, quality of life (QoL), and other comorbidities in older Ugandans living with HIV remain under-explored.

Methods: We analyzed data from three annual assessments of older people living with HIV (PLWH) and age- and sex-similar people not living with HIV (PnLWH). We fitted linear generalized estimating equations (GEE) regression models to estimate the correlates of PA, including demographics, frailty, QoL, HIV, and other comorbidities.

Stepwise order in protein complex assembly: approaches and emerging themes.

Protein-based nanomachines drive every cellular process. An explosion of high-resolution structures of multiprotein complexes has improved our understanding of what these machines look like and how they work, but we still know relatively little about how they assemble in living cells. For example, it has only recently been appreciated that many complexes assemble co-translationally, with at least one subunit still undergoing active translation while already interacting with other subunits.

The Combined Effect of Multisensory Stimulation and Therapist Support on Physical and Mental Health of Older Adults Living in Nursing Homes: Pilot Randomized Controlled Trial.

Background: Increasing life expectancy has led to a rise in nursing home admissions, a context in which older adults often experience chronic physical and mental health conditions, chronic pain, and reduced well-being. Nonpharmacological approaches are especially important for managing older adults' chronic pain, mental health conditions (such as anxiety and depression), and overall well-being, including sensory stimulation (SS) and therapist support (TS). However, the combined effects of SS and TS have not been investigated.

Development and validation of a pragmatic measure of cocreation in research engagement: a study protocol.

Introduction: Cocreation, a collaborative process of key interested partners working alongside researchers, is fundamental to community-engaged research. However, the field of community-engaged research is currently grappling with a significant gap: the lack of a pragmatic and validated measure to assess the quality of this process. This protocol addresses this significant gap by developing and testing a pragmatic cocreation measure with diverse community and research partners involved in participatory health-related research.

Dry eye post-cataract surgery: a systematic review and meta-analysis.

Significance: Cataract surgery is one of the most performed surgical procedures worldwide. As a potential complication following cataract surgery, dry eye has the potential to impact visual outcomes, lower patient satisfaction, and be detrimental to quality of life.

Purpose: To evaluate the effect of cataract surgery on dry eye outcomes postoperatively.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Evaluation of a Program Designed to Support Implementation of Prescribing Medication for Treatment of Opioid Use Disorder in Primary Care Practices.

Purpose: Offering medication for opioid use disorder (MOUD) in primary care can increase access to effective opioid use disorder treatment and help address the US opioid crisis. We describe a primary care office-based opioid treatment program and addiction consultation service model designed to support small, rural clinics to increase their capacity for MOUD.

Methods: This is an evaluation of an intervention to increase clinic capacity to offer MOUD.