Spatially dependent tissue distribution of thyroid hormones by plasma thyroid hormone binding proteins.

Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings.

Expiration of a state level eviction moratorium in the first or second trimester of pregnancy and perinatal outcomes among Medicaid and uninsured people, 2020-2022.

Goal: Housing insecurity is associated with poor perinatal outcomes. However, we lack information on whether supportive housing policies improve perinatal health. Our goal was to estimate the effect of expiration of a state-level eviction moratoria on adverse maternal and infant outcomes among Medicaid insured individuals residing in states with a state-level moratorium in place at conception in the United States.

Is Racism a Barrier to HIV Care Continuum Engagement among Black People in the US?: A Scoping Review to Assess the State of the Science and Inform a Research Agenda.

People living with HIV (PLWH) can achieve VS through timely HIV care continuum (HCC) engagement (ie, diagnosis, linkage to HIV care, retention in care and adherence to prescribed treatment regimens). Black populations have poorer VS, suboptimal HCC engagement and higher levels of racism-related mistrust. This paper assessed the state of the evidence linking sub-optimal HCC engagement to racism among US Black populations.

Perceptions and Needs for a Technology-Based Dyadic Intervention on Symptom Management Among Patients With Colorectal Cancer and Their Caregivers: A Qualitative Study.

Background: Colorectal cancer (CRC) patients and their caregivers often experience multiple co-occurring symptoms (eg, fatigue, depression, anxiety, and sleep disturbance). There is a noticeable gap in research regarding symptom management for patient-caregiver dyads, particularly using technology-based tools.

Objective: This study aimed to describe the needs and perceptions of patient-caregiver dyads regarding a technology-based tool to manage their multiple symptoms.

Empowering Graph Neural Network-Based Computational Drug Repositioning with Large Language Model-Inferred Knowledge Representation.

Computational drug repositioning, through predicting drug-disease associations (DDA), offers significant potential for discovering new drug indications. Current methods incorporate graph neural networks (GNN) on drug-disease heterogeneous networks to predict DDAs, achieving notable performances compared to traditional machine learning and matrix factorization approaches. However, these methods depend heavily on network topology, hampered by incomplete and noisy network data, and overlook the wealth of biomedical knowledge available.

Cell-based therapies reverse the heart failure-altered right ventricular proteome.

Background: Congenital heart defects can lead to right ventricular (RV) pressure-overload and heart failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) have been studied clinically as options to restore heart function in disease states. Many studies have indicated these cells act through paracrine mechanisms to prevent apoptosis, promote cellular function, and regulate gene/protein expression.

Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures.

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures.

Impact of high-dose cholecalciferol (vitamin D3) and inulin prebiotic on intestinal and airway microbiota in adults with cystic fibrosis: A 2 × 2 randomized, placebo-controlled, double-blind pilot study.

Background: Cystic fibrosis (CF) is a multi-organ disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with CF often have gastrointestinal (GI) dysbiosis due to chronic inflammation and antibiotic use. Previous studies suggested a role for vitamin D in reversing the GI dysbiosis found in CF.

Sound-seeking before and after hearing loss in mice.

How we move our bodies affects how we perceive sound. For instance, head movements help us to better localize the source of a sound and to compensate for asymmetric hearing loss. However, many auditory experiments are designed to restrict head and body movements.

Centrocortin potentiates co-translational localization of its mRNA to the centrosome via dynein.

Centrosomes rely upon proteins within the pericentriolar material to nucleate and organize microtubules. Several mRNAs also reside at centrosomes, although less is known about how and why they accumulate there. We previously showed that local () mRNA supports centrosome separation, microtubule organization, and viability in embryos.

Preclinical Evaluation of Sigma 1 Receptor Antagonists as a Novel Treatment for Painful Diabetic Neuropathy.

The global prevalence of diabetes is steadily rising, with an estimated 537 million adults affected by diabetes in 2021, projected to reach 783 million by 2045. A severe consequence of diabetes is the development of painful diabetic neuropathy (PDN), afflicting approximately one in every three diabetic patients and significantly compromising their quality of life. Current pharmacotherapies for PDN provide inadequate pain relief for many patients, underscoring the need for novel treatments that are both safe and effective.

SAFE-OPT: a Bayesian optimization algorithm for learning optimal deep brain stimulation parameters with safety constraints.

To treat neurological and psychiatric diseases with deep brain stimulation (DBS), a trained clinician must select parameters for each patient by monitoring their symptoms and side-effects in a months-long trial-and-error process, delaying optimal clinical outcomes. Bayesian optimization has been proposed as an efficient method to quickly and automatically search for optimal parameters. However, conventional Bayesian optimization does not account for patient safety and could trigger unwanted or dangerous side-effects.

A biallelic variant of the RNA exosome gene, EXOSC4, associated with neurodevelopmental defects impairs RNA exosome function and translation.

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Pathogenic variants in EXOSC genes, which encode structural subunits of this complex, are linked to several autosomal recessive disorders. Here, we describe a missense allele of the EXOSC4 gene that causes a collection of clinical features in two affected siblings.

Testosterone concentrations and associated predictors in men with cystic fibrosis: A retrospective, single-center study.

Background: Men with cystic fibrosis (CF) have sexual health concerns such as delayed puberty, infertility, and hypogonadism. The causes and prevalence of hypogonadism have not been well studied. The purpose of this study was to determine the prevalence of a low testosterone concentration in men with CF.

The RNA-binding protein Nab2 regulates levels of the RhoGEF Trio to govern axon and dendrite morphology.

The RNA-binding protein (RBP) Nab2 acts in neurons to regulate neurodevelopment and is orthologous to the human intellectual disability-linked RBP, ZC3H14. Nab2 governs axon projection in mushroom body neurons and limits dendritic arborization of class IV sensory neurons in part by regulating splicing events in ∼150 mRNAs. Analysis of the () mRNA revealed that Nab2 promotes an exon-skipping event and regulates mA methylation on pre-mRNA by the Mettl3 methyltransferase.

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

Background: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely.

Caregiver greeting to infants under 6 months already reflects emerging differences in those later diagnosed with autism.

As infants develop, caregivers adjust their behaviour to scaffold their infant's emerging skills, such that changes in infants' social abilities are expected to elicit changes in caregiver behaviour. We examined whether changes in the probability of infant-directed caregiving behaviour-specifically, greeting, a ubiquitous signal used by caregivers to initiate reciprocal interactions-differ between infant-caregiver dyads with an infant later diagnosed with autism and dyads with a neurotypically developing infant during infants' first 6 months. Using longitudinal data from 163 dyads, we found that caregivers in autism dyads ( = 40) used greeting less and at later infant ages than caregivers with a neurotypically developing infant (neurotypical dyads, = 83).

Targeting PKCα alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin.

Ferroportin (Fpn) is the only iron exporter, playing a crucial role in systemic iron homeostasis. Fpn is negatively regulated by its ligand hepcidin, but other potential regulators in physiological and disease conditions remain poorly understood. Diabetes is a metabolic disorder that develops body iron loading with unknown mechanisms.

Contextualizing Inequities in COVID Vaccination Trends Among Project REFOCUS Pilot Sites: Racism-Related Determinants of Health.

Introduction: Coronavirus disease (COVID) dashboards rarely provide insights about the racialized contexts in which vaccination inequities occur.

Objective: The purpose of this study was to use the emerging Project REFOCUS dashboard to contextualize COVID vaccination patterns among 6 diverse communities.

Methods: We queried the dashboard to generate descriptive statistics on vaccination trends and racism-related contextual factors among the 6 Project REFOCUS pilot sites (Albany, Georgia, Bronx, New York, Detroit, Michigan, Helena-West Helena, Arkansas, San Antonio, Texas, and Wake County, North Carolina).

Physical and Psychological Burden among Caregivers of Latinx Older Adults with Stroke and Multimorbidity.

Objective: To investigate the association between Latinx older adults' stroke, multimorbidity, and caregiver burden.

Methods: For this retrospective cohort study, we used the Hispanic Established Populations for the Epidemiologic Study of the Elderly (H-EPESE) Wave-7 data set. The caregiver's physical burden was defined by using the Level of Burden Index.