Placental Gene Therapy for Fetal Growth Restriction and Preeclampsia: Preclinical Studies and Prospects for Clinical Application.

In the last three decades, gene therapy has demonstrated significant progress. Over 700 active investigational new drug (IND) applications have been reported. Research on in utero gene therapy has advanced, but ethical and safety concerns persist.

Association of Atrial Fibrillation and Cognitive Dysfunction: A Comprehensive Narrative Review of Current Understanding and Recent Updates.

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. The prevalence of both AF and dementia is steadily rising and is expected to rise further in the coming decades. There is increasing evidence to suggest an association between AF and various degrees of cognitive dysfunction, from mild cognitive impairment to severe dementia.

Securing human resources for Japan's aging population: a mixed methods study of job satisfaction and well-being among Southeast Asian long-term care workers in Japan.

Background: Japan is one of the countries experiencing a "super-aged society." The government has looked to Southeast Asia for recruiting workers to fill the demand for long-term care (LTC) workers. However, migrant LTC workers have faced many job-related stressors.

Effects of GBT1118, a voxelotor analog, on bone disease in sickle cell disease mice.

We assessed the effect of GBT1118, a sickle hemoglobin polymerization inhibitor on bone loss in humanized sickle cell disease (SCD) mice. Healthy control (Ctrl) 4-months-old female and male mice were fed Vehicle-chow for 2-months, while SCD mice were fed Vehicle-chow or GBT1118-chow. By micro-CT, GBT1118 significantly increased femur metaphyseal trabecular thickness (Tb.

A National Survey of Obstetrics and Gynecology Resident Perspectives on Their Preparedness to Provide Care for Underserved Patients with Gynecologic Malignancies.

Obstetrics and Gynecology (Ob/Gyn) residents will encounter, screen for, and diagnose gynecologic malignancies. This survey assessed residents' confidence in providing NCCN Guidelines-based care to Gynecologic Oncology patients of differing racial/ethnic backgrounds and insurance statuses while accounting for residents' backgrounds. An anonymous, novel Qualtrics survey was disseminated to current US Ob/Gyn residents, with multiple-choice questions about subject demographics and Likert scale questions about their readiness to care for diverse patients.

Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation.

RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc-finger families. We show that multiple ZFPs are previously unknown regulators of RNA splicing, alternative polyadenylation, stability, or translation.

Liquid Biopsy in Neuropsychiatric Disorders: A Step Closer to Precision Medicine.

Psychiatric disorders are among the leading causes of disease burden worldwide. Despite their significant impact, their diagnosis remains challenging due to symptom heterogeneity, psychiatric comorbidity, and the lack of objective diagnostic tests and well-defined biomarkers. Leveraging genomic, epigenomic, and fragmentomic technologies, circulating cell-free DNA (ccfDNA)-based liquid biopsies have emerged as a potential non-invasive diagnosis and disease-monitoring tool.

The backbone NMR resonance assignments of the stabilized E. coli β clamp.

The 81 kDa E. coli β clamp is a ring-shaped head-to-tail homodimer that encircles DNA and plays a central role in bacterial DNA replication by serving as a processivity factor for DNA polymerases and a binding platform for other DNA replication and repair proteins. Here we report the backbone H, N, and C NMR resonance assignments of the stabilized T45R/S107R β clamp variant obtained using standard TROSY-based triple-resonance experiments (BMRB 52548).

Autoregulated splicing of β programs T cell fate in response to antigen-receptor stimulation.

T cell receptor (TCR) sensitivity to peptide-major histocompatibility complex (MHC) dictates T cell fate. Canonical models of TCR sensitivity cannot be fully explained by transcriptional regulation. In this work, we identify a posttranscriptional regulatory mechanism of TCR sensitivity that guides alternative splicing of TCR signaling transcripts through an evolutionarily ultraconserved poison exon (PE) in the RNA-binding protein (RBP) TRA2β in mouse and human.

PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals.

To support PTM proteomic analysis and annotation in different species, we developed PTMoreR, a user-friendly tool that considers the surrounding amino acid sequences of PTM sites during BLAST, enabling a motif-centric analysis across species. By controlling sequence window similarity, PTMoreR can map phosphoproteomic results between any two species, perform site-level functional enrichment analysis, and generate kinase-substrate networks. We demonstrate that the majority of real P-sites in mice can be inferred from experimentally derived human P-sites with PTMoreR mapping.

Benefits of In Situ Foamed and Printed Porous Scaffolds in Wound Healing.

Macroporous hydrogels have shown significant promise in biomedical applications, particularly regenerative medicine, due to their enhanced nutrient and waste permeability, improved cell permissibility, and minimal immunogenicity. However, traditional methods of generating porous hydrogels require secondary post-processing steps or harmful reagents making simultaneous fabrication with bioactive factors and cells impossible. Therefore, a handheld printer is engineered for facile and continuous generation and deposition of hydrogel foams directly within the skin defect to form defect-specific macroporous scaffolds.

Open Bankart Repair: Technique and Outcomes for the High-Level Athlete.

Historically considered the gold standard technique for glenohumeral instability, the open Bankart repair is being performed at decreased rates because of the current trends favoring arthroscopic Bankart repair and the lack of consistent training of the open technique. However, open Bankart repairs may be more appropriate for certain high-risk populations (ie, high-level collision athletes) because of their reduced recurrent instability rates. Further investigations are needed to identify the indications for arthroscopic versus open Bankart repair and compare their outcomes in high-level athletes.

Baseline sLAG-3 levels in Caucasian and African-American breast cancer patients.

Background: Worse survival persists for African-Americans (AA) with breast cancer compared to other race/ethnic groups despite recent improvements for all. Unstudied in outcomes disparities to date is soluble LAG-3 (sLAG-3), cleaved from the LAG-3 immune checkpoint receptor which is a proposed target for deactivation in emerging immunotherapies due to its prominent immunosuppressive function in the tumoral microenvironment. A prior study has found that lower sLAG-3 baseline level was associated with poor outcomes.

Parental Sexual Socialization, Sexual Subjectivity, and Emotional Responses to Sexual Experiences among Adolescent Girls.

This study explored girls' sexual subjectivity as a pathway through which parental socialization influenced their emotions about past sexual experiences. A national online survey of 397 adolescent girls (M = 16.8 years) from diverse racial/ethnic backgrounds (33.

Evaluation of Pain-Associated Behavioral Changes in Monoiodoacetate-Induced Osteoarthritic Rats Using Dynamic Weight Bearing Analysis.

Pain is the primary clinical indication of osteoarthritis (OA), and behavioral assessments in rodent pain models are widely used to understand pain patterns. These preclinical pain assessments can also help us to understand the effectiveness of emerging therapeutics for prolonged OA pain management. Along with evoked methods like mechanical allodynia and thermal hyperalgesia, non-evoked methods such as dynamic weight bearing (DWB) analysis are valuable tools for behavioral assessments of pain.

Monitoring Circulating Myeloid Cells in Peritonitis with an In Vivo Imaging Flow Cytometer.

Peritonitis is a common and life-threatening inflammatory disease. Myeloid cells are elevated in the peripheral blood and contribute to peritonitis, but their circulating dynamics are not clear. In vivo flow cytometry (IVFC) is a noninvasive technique for monitoring the dynamics of circulating cells in live animals.

Leptospira interrogans encodes a canonical BamA and three novel noNterm Omp85 outer membrane protein paralogs.

The Omp85 family of outer membrane proteins are ubiquitously distributed among diderm bacteria and play essential roles in outer membrane (OM) biogenesis. The majority of Omp85 orthologs are bipartite and consist of a conserved OM-embedded 16-stranded beta-barrel and variable periplasmic functional domains. Here, we demonstrate that Leptospira interrogans encodes four distinct Omp85 proteins.

Single Acetylation-mimetic Mutation in TDP-43 Nuclear Localization Signal Disrupts Importin α1/β Signaling.

Cytoplasmic aggregation of the TAR-DNA binding protein of 43 kDa (TDP-43) is the hallmark of sporadic amyotrophic lateral sclerosis (ALS). Most ALS patients with TDP-43 aggregates in neurons and glia do not have mutations in the TDP-43 gene but contain aberrantly post-translationally modified TDP-43. Here, we found that a single acetylation-mimetic mutation (K82Q) near the TDP-43 minor Nuclear Localization Signal (NLS) box, which mimics a post-translational modification identified in an ALS patient, can lead to TDP-43 mislocalization to the cytoplasm and irreversible aggregation.

Community-level bystander treatment and outcomes for witnessed out-of-hospital cardiac arrest in the state of Connecticut.

Background: Prior reports have demonstrated underutilization of bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use in patients with witnessed out-of-hospital cardiac arrest (OHCA) in Connecticut. This study aimed to identify community-level risk factors that contribute to low rates of bystander intervention to improve statewide OHCA outcomes.

Methods: We analyzed 2,789 adult patients with witnessed, non-traumatic OHCA submitted to the Connecticut Cardiac Arrest Registry to Enhance Survival (CARES) between 2013-2022.

Reaction to at-home air purifiers installed to reduce traffic-related air pollution in near-highway residences.

Background And Aim: Traffic-related ultrafine particle pollution near highways is associated with adverse health. Reducing exposure by use of portable air purifiers in homes is one approach to reducing this risk. However, the reaction of residents to having air purifiers in homes is not well studied.

LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of Parkinson's disease (PD) to date. Dysfunction in LRRK2 enzymatic activities and elevated protein levels are associated with the disease. How is LRRK2 activated, and what downstream molecular and cellular processes does LRRK2 regulate? Addressing these questions is crucial to decipher the disease mechanisms.

"I'm not very skilled in using gadgets:" A qualitative exploration of the facilitators and barriers to using telepharmacy services among Filipino senior citizens.

Background: Telepharmacy provides remote care by pharmacists to distant patients via telecommunications. It is a new service used in the Philippines during the COVID-19 pandemic. However, its utilization among vulnerable populations, notably senior citizens, remains relatively unexplored.

Deliberative Behaviors and Prefrontal-Hippocampal Coupling are Disrupted in a Rat Model of Fetal Alcohol Spectrum Disorders.

Fetal alcohol spectrum disorders (FASDs) are characterized by a range of physical, cognitive, and behavioral impairments. Determining how temporally specific alcohol exposure (AE) affects neural circuits is crucial to understanding the FASD phenotype. Third trimester AE can be modeled in rats by administering alcohol during the first two postnatal weeks, which damages the medial prefrontal cortex (mPFC), thalamic nucleus reuniens, and hippocampus (HPC), structures whose functional interactions are required for working memory and executive function.