Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation.

Long-lasting vaginal dosage forms could improve the therapeutic efficacy of vaginal microbicides, but achieving long-term delivery to the vaginal canal has been a significant challenge. To advance understanding of vaginal dosage retention and biodistribution, we describe a method of noninvasive imaging with Zr-labeled bioadhesive nanoparticles (BNPs) in non-human primates. We additionally examined the safety of repeated BNP application.

A Novel and Comprehensive Wellness Assessment for Lifestyle-Based Interventions.

Objective: While weight status and clinical laboratory measures are important in assessing obesity-related disease severity and chronic disease risk, including a broader range of emotional, psychosocial, and behavioral factors would provide greater context of an individual's overall state of wellness and could be used to better guide treatment decisions. The purpose of this research was to develop a comprehensive Lifestyle Wellness assessment for use in lifestyle-based wellness interventions and programs.

Methods: A cross-sectional exploratory factor analysis (EFA) was conducted using baseline data from  = 138 adults participating in behavioral weight loss trials.

Cardiomyocyte-Specific Overexpression of Activated Yes-Associated Protein Modified-RNA Promotes Cardiomyocyte Proliferation and Myocardial Regeneration.

Background: The proliferative capacity of cardiomyocytes in adult mammalian hearts is far too low to replace the cells that are lost to myocardial infarction. Both cardiomyocyte proliferation and myocardial regeneration can be improved via the overexpression of a constitutively active variant of YAP5SA (Yes-associated protein, 5SA [active] mutant), but persistent overexpression of proliferation-inducing genes could lead to hypertrophy and arrhythmia, whereas off-target expression in fibroblasts and macrophages could increase fibrosis and inflammation.

Methods And Results: Transient overexpression of YAP5SA or GFP (green fluorescent protein; control) was targeted to cardiomyocytes via our cardiomyocyte-specific modified mRNA translation system (CM-SMRTs or CM-SMRTs, respectively).

Procedural Volume and Outcomes After Septal Reduction Therapies in Hypertrophic Obstructive Cardiomyopathy.

Background: Septal myectomy and alcohol septal ablation (ASA) are septal reduction therapies for patients with symptomatic obstructive hypertrophic cardiomyopathy. Operator and hospital volume may influence outcomes, but contemporary data on this relationship are limited.

Methods And Results: This retrospective cohort study used data from the Vizient Clinical Data Base (2016-2022).

Hypertension Severity as Quantified by Hypertension Daily Dose and Blood Pressure With Risk of Stroke in REGARDS.

Background: It is unknown how blood pressure (BP) relates to stroke risk across levels of hypertension daily dose (HDD)-quantified antihypertensive medication intensity.

Methods And Results: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study enrolled 30 239 participants from the 48 contiguous US states in 2003 to 2007 with in-person follow-up in 2013 to 2016 (Visit 2). We included those without prior stroke at Visit 2, treating this visit as T.

Evaluation of socioecological factors on health behaviors and weight change during major life event: A cross-sectional study using data collected during the COVID-19 pandemic.

Background: Socioecological factors are associated with key health behaviors that are critical for weight management, and major life events may disrupt engagement in these behaviors. However, the influence of socioecological factors on health behaviors in the midst of major life events is not clear and is difficult to study due to the random and sporadic nature of their occurrence. The COVID-19 pandemic provided a unique opportunity to study a major life event and its impacts on diet, physical activity, and body weight.

Species distribution models predict genetic isolation of Hagen in Selys, 1853 (Odonata, Calopterygidae).

Understanding how past and current environmental conditions shape the demographic and genetic distributions of organisms facilitates our predictions of how future environmental patterns may affect populations. The Canyon Rubyspot damselfly (Odonata: Zygoptera: ) is an insect with a range distribution from Colombia to the arid southwestern United States, where it inhabits shaded mountain streams in the arid southwestern United States. Past spatial fragmentation of habitat and limited dispersal capacity of may cause population isolation and genetic differentiation, and projected climate change may exacerbate isolation by further restricting the species' distribution.

Association Between Caregiver Strain and Self-Care Among Caregivers With Hypertension: Findings From the REGARDS Study.

Background: Self-care for adults with hypertension includes adherence to lifestyle behaviors and medication. For unpaid caregivers with hypertension, the burden of family caregiving may adversely impact self-care. We examined the association between caregiver strain and hypertension self-care among caregivers with hypertension.

Stroke Severity, Caregiver Feedback, and Cognition in the REGARDS-CARES Study.

Background: Cognitive impairment after stroke is common and is present in up to 60% of survivors. Stroke severity, indicated by both volume and location, is the most consequential predictor of cognitive impairment, with severe strokes predicting higher chances of cognitive impairment. The current investigation examines the associations of 2 stroke severity ratings and a caregiver-report of poststroke functioning with longitudinal cognitive outcomes.

Bone marrow-fibroblast progenitor cell-derived small extracellular vesicles promote cardiac fibrosis via miR-21-5p and integrin subunit αV signalling.

Cardiac fibrosis is the hallmark of cardiovascular disease (CVD), which is leading cause of death worldwide. Previously, we have shown that interleukin-10 (IL10) reduces pressure overload (PO)-induced cardiac fibrosis by inhibiting the recruitment of bone marrow fibroblast progenitor cells (FPCs) to the heart. However, the precise mechanism of FPC involvement in cardiac fibrosis remains unclear.

Differential effectiveness of COVID-19 health behaviors: The role of mental health conditions in mask-wearing, social distancing, and hygiene practice.

Background: Mental health conditions are known to increase susceptibility to infectious diseases, including coronavirus disease 2019 (COVID-19). Health behaviors play a crucial role in mitigating this susceptibility. We aim to examine the differential effectiveness of COVID-19 preventive health behaviors among individuals, considering the presence or absence of specific mental health disorders.

Low-dose decitabine plus venetoclax as post-transplant maintenance for high-risk myeloid malignancies.

Relapse remains a major cause of treatment failure following allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We retrospectively investigated low-dose decitabine and venetoclax (DEC/VEN) as post-transplant maintenance in 26 older patients with AML and MDS. The cumulative incidence of day 100 gIII-IV acute graft versus host disease (GVHD) and 1-year moderate-severe chronic GVHD was 5% and 26%, respectively.

Preparation of von Hippel-Lindau (VHL) E3 ubiquitin ligase ligands exploiting constitutive hydroxyproline for benzylic amine protection.

The von Hippel-Lindau (VHL) protein serves as the substrate recognition subunit of the multi-subunit Cullin-2 RING E3 ubiquitin ligase (CRL2), which regulates intracellular concentrations of hypoxia inducible factors (HIFs) through a ubiquitin proteasome system (UPS) cascade. Strategic recruitment of CRL2 by bi- or trifunctional targeted protein degraders (, PROTACs®) offers the prospect of promoting aberrant polyubiquitination and ensuing proteasomal degradation of disease-related proteins. Non-peptidic, l-hydroxyproline-bearing VHL ligands such as VH032 (1) and its chiral benzylic amine analog Me-VH032 (2), are functional components of targeted protein degraders commonly employed for this purpose.