Psychosocial Support Needs and Preferences Among Family Caregivers of ICU Patients with Severe Acute Brain Injury: A Qualitative Thematic Analysis.

Background: Family caregivers of patients with severe acute brain injury (SABI) are at risk for clinically significant chronic emotional distress, including depression, anxiety, and posttraumatic stress. Existing psychosocial interventions for caregivers of intensive care unit (ICU) patients are not tailored to the unique needs of caregivers of patients with SABI, do not demonstrate long-term efficacy, and may increase caregiver burden. In this study, we explored the needs and preferences for psychosocial services among SABI caregivers to inform the development and adaptation of interventions to reduce their emotional distress during and after their relative's ICU admission.

Distinct molecular and clinical features of specific variants of KRAS codon 12 in pancreatic adenocarcinoma.

PURPOSE Oncogenic mutations in KRAS have been identified in > 85% of pancreatic ductal adenocarcinoma (PDAC) cases. G12D, G12V, and G12R are the most frequent variants. Using large clinical and genomic databases, this study characterizes prognostic and molecular differences between KRAS variants, focusing on KRAS G12D and G12R.

Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

Recent Advances in the Genetics of Ataxias: An Update on Novel Autosomal Dominant Repeat Expansions.

Purpose Of Review: Autosomal dominant cerebellar ataxias, also known as spinocerebellar ataxias (SCAs), are genetically and clinically diverse neurodegenerative disorders characterized by progressive cerebellar dysfunction. Despite advances in sequencing technologies, a large proportion of patients with SCA still lack a definitive genetic diagnosis. The advent of advanced bioinformatic tools and emerging genomics technologies, such as long-read sequencing, offers an unparalleled opportunity to close the diagnostic gap for hereditary ataxias.

Quantification of the Anterior-Centripetal Movement of the Ciliary Muscle During Accommodation Using Dynamic OCT Imaging.

Purpose: Although the lens undoubtedly plays a major role in presbyopia, altered lens function could be in part secondary to age-related changes of the ciliary muscle. Ciliary muscle changes with accommodation have been quantified using optical coherence tomography, but so far these studies have been limited to quantifying changes in ciliary muscle thickness, mostly at static accommodative states. Quantifying ciliary muscle thickness changes does not effectively capture the dynamic anterior-centripetal movement of the ciliary muscle during accommodation.

Early Versus Late Atrial Fibrillation Recurrence After Pulsed Field Ablation: Insights From the admIRE Trial.

Background And Aims: Studies have shown correlations between early recurrence (ER) and late recurrence (LR) of atrial arrhythmia after ablation with thermal technologies. This admIRE trial (NCT05293639) subanalysis aims to analyze ER versus LR in patients with paroxysmal atrial fibrillation (PAF) undergoing pulsed field ablation (PFA).

Methods: Patients with symptomatic paroxysmal atrial fibrillation and ≥1 transtelephonic monitoring transmission during the blanking period were included (n=169).

The FBXO45-GEF-H1 axis controls germinal center formation and B-cell lymphomagenesis.

The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation.

Improving reading competence in aphasia with combined aerobic exercise and phono-motor treatment: Protocol for a randomized controlled trial.

Aphasia, a communication disorder caused primarily by left-hemisphere stroke, affects millions of individuals worldwide, with up to 70% experiencing significant reading impairments. These deficits negatively impact independence and quality of life, highlighting the need for effective treatments that target the cognitive and neural processes essential to reading recovery. This Randomized Clinical Trial (RCT) aims to test the efficacy of a combined intervention incorporating aerobic exercise training (AET) and phono-motor treatment (PMT) to enhance reading recovery in individuals with post-stroke aphasia.

Mice develop obesity and lose myocardial metabolic flexibility months after exertional heat stroke.

As global temperatures rise, heat-related chronic health disorders are predicted to become more prevalent. We tested whether a single exposure to acute heat illness, using a preclinical mouse model of exertional heat stroke (EHS), can induce late-emerging health disorders that progress into chronic disease. Following EHS, mice were followed for 3 months; after two weeks of recovery, half were placed on a Western diet to determine if previous EHS exposure amplifies the negative consequences of an atherogenic diet.

Developing an alternative medium for in-space biomanufacturing.

In-space biomanufacturing provides a sustainable solution to facilitate long-term, self-sufficient human habitation in extraterrestrial environments. However, its dependence on Earth-supplied feedstocks renders in-space biomanufacturing economically nonviable. Here, we develop a process termed alternative feedstock-driven in-situ biomanufacturing (AF-ISM) to alleviate dependence on Earth-based resupply of feedstocks.

Effect of Childhood Adversity on the Relationship Between Family Resilience and Behavioral or Conduct Problems in Children With Special Healthcare Needs.

Objective: Behavioral or conduct problems (BCPs) are common co-occurring conditions in children with special health care needs (CSHCNs), affecting their developmental and functional milestones. The role of family resilience in mitigating BCPs among these children and how adverse childhood experiences (ACEs) affect this dynamic remain largely unclear. The aim of the study was to disentangle the complex interplay between family resilience, ACEs, and BCPs by examining how ACEs moderate the relationship between family resilience and BCPs.

Developing and Assessing a Scalable Digital Health Tool for Pretest Genetic Education in Patients With Early-Onset Colorectal Cancer: Mixed Methods Design.

Background: National guidelines recommend germline genetic testing (GT) for all patients with early-onset colorectal cancer. With recent advances in targeted therapies and GT, these guidelines are expected to expand to include broader groups of patients with colorectal cancer. However, there is a shortage of genetic professionals to provide the necessary education and support for informed consent.

Comparing Five Generations of ActiGraph Devices using an Orbital Shaker.

Introduction: ActiGraph accelerometers are used extensively to objectively assess physical activity, sedentary behavior, and sleep. Here, we present an objective validation of five generations of ActiGraph sensors to characterize potential differences in output arising from changes to hardware or firmware.

Methods: An orbital shaker generated accelerations from 0 to 3700 milli-g in a randomized order to test the wGT3X-BT, GT9X, CentrePoint Insight Watch (CPIW) 1.

Assessment, Decision, Adaptation, Production, Topical Experts-Integration, Training, and Testing (ADAPT-ITT) Framework to Tailor Evidence-Based Posttraumatic Stress Disorder Treatment for People With HIV to Enhance Engagement and Adherence: Qualitative Results from a Feasibility Randomized Controlled Trial.

Background: Individuals with co-occurring posttraumatic stress disorder (PTSD) and HIV are at high-risk for negative HIV-related outcomes, including low adherence to antiretroviral therapy, faster disease progression, more hospitalizations, and almost twice the rate of death. Despite high rates of PTSD in persons with HIV (PWH) and poor HIV-related health outcomes associated with PTSD, an effective evidence-based treatment for PTSD symptoms in PWH does not exist.

Objective: This study aimed to describe the adaptation and theater testing of an evidence-based intervention designed for people with co-occurring PTSD and HIV.

Use of disease modifying anti-rheumatic drugs and risk of multiple myeloma in US Veterans with rheumatoid arthritis.

Background: Biologic (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) used in the management of rheumatoid arthritis (RA) target inflammatory pathways implicated in the pathogenesis of multiple myeloma (MM). It is unknown whether use of b/tsDMARDs affects the incidence of MM.

Methods: In this cohort study using Veterans Health Administration (VHA) data, we identified Veterans newly diagnosed with RA from 1/1/2002 to 12/31/2018 using diagnostic codes and medication fills.

Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial.

Background: Olutasidenib is a potent, selective, oral, small molecule inhibitor of mutant IDH1 (mIDH1) which induced durable remissions in high-risk, relapsed/refractory (R/R) mIDH1 AML patients in a phase 1/2 trial. We present a pooled analysis from multiple cohorts of the phase 1/2 trial of patients with R/R AML who received combination olutasidenib and azacitidine therapy.

Methods: Adult patients with mIDH1 AML received 150 mg olutasidenib twice daily plus standard-of-care azacitidine (OLU + AZA) and were evaluated for response and safety.

Genotyped cluster investigations versus standard contact tracing: comparative impact on latent tuberculosis infection cascade of care in a low-incidence region.

Background: Cluster and contact investigations aim to identify and treat individuals with tuberculosis (TB) and latent TB infection (LTBI). Although genotyped cluster investigations may be superior to contact investigations in generating additional epidemiological links, this may not necessarily translate into reducing infections. Here, we investigated the impact of genotyped cluster investigations compared to standard contact investigations on the LTBI care cascade in a low incidence setting.

Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability.

Traumatic brain injury is a leading cause of chronic neurologic disability and a risk factor for development of neurodegenerative disease. However, little is known regarding the pathophysiology of human traumatic brain injury, especially in the window after acute injury and the later life development of progressive neurodegenerative disease. Given the proposed mechanisms of toxic protein production and neuroinflammation as possible initiators or contributors to progressive pathology, we examined phosphorylated tau accumulation, microgliosis and astrogliosis using immunostaining in the orbitofrontal cortex, a region often vulnerable across traumatic brain injury exposures, in an age and sex-matched cohort of community traumatic brain injury including both mild and severe cases in midlife.

Longitudinal Analysis of Cardiovascular Risk Factors Among Older Adults Participating in a Park-Based Fitness Program.

Physical inactivity is a major risk factor for noncommunicable diseases, particularly among older adults. We examined changes in cardiovascular risk factors among older adults in a community-based fitness program in Miami-Dade County, FL. We used repeated measures linear mixed models to examine participants' cardiovascular risk factor changes over 28 months.

Conducting Clinical Research in Low Research Resource Countries: Lessons Learned From the International Registry of Men With Advanced Prostate Cancer Study in Nigeria.

Purpose: There is limited cancer clinical research in sub-Saharan African countries despite the significant burden of cancers. The primary objective of this strengths, weaknesses, opportunities, and threats (SWOT) analysis was to understand and document factors affecting the successful implementation of prostate cancer (CaP) clinical research in Nigeria.

Methods: The research team used a qualitative design involving International Registry of Men with Advanced Prostate Cancer (IRONMAN) study team members as participants from four regional sites in Nigeria.

Person-Centered Social Determinants and Neighborhood-Level Deprivation Associated With Disability in Hispanic People With Multiple Sclerosis.

Background And Objectives: Multiple sclerosis (MS)-related disability in Hispanic people with MS is associated with inequities in social determinants of health (SDOH) as measured by composite indices of areal-level census data. Studies of individual-level measures of SDOH are lacking. This study examined the separate and joint effects of person-centered SDOH indicators and an area-level composite on MS disability measures.

Effects of leg immobilization and recovery resistance training on skeletal muscle-molecular markers in previously resistance trained versus untrained adults.

We sought to examine how resistance training (RT) status in young healthy individuals, either well resistance trained (T, n=10) or untrained (UT, n=11), affected molecular markers with leg immobilization followed by recovery RT. All participants underwent two weeks of left leg immobilization via a locking leg brace. Afterwards, all participants underwent eight weeks (3 d/week) of knee extensor focused progressive RT.