Aberrant DNA methylation of genes regulating CD4+ T cell HIV-1 reservoir in women with HIV.

Background: The HIV-1 reservoir in CD4+ T cells (HR) pose a major challenge to curing HIV, with many of its mechanisms still unclear. HIV-1 DNA integration and immune responses may alter the host's epigenetic landscape, potentially silencing HIV-1 replication.

Methods: This study used bisulphite capture DNA methylation sequencing in CD4+ T cells from the blood of 427 virally suppressed women with HIV to identify differentially methylated sites and regions associated with HR.

Caution in Handling Switchers in Pharmacoepidemiologic Studies Estimating Treatment Effects: The Example of Dipeptidyl Peptidase-4 Inhibitors and Inflammatory Bowel Disease.

Real-world evidence assessing dipeptidyl peptidase-4 inhibitors (DPP4i)'s risk of inflammatory bowel disease (IBD) is conflicting. One study modelling DPP4i as a time varying exposure (TVE) observed a harmful effect in a UK population, while an active-comparator new-user (ACNU) study observed a null effect in a US population. To assess the impact of study design in estimating treatment effect, we implemented both designs in the UK Clinical Practice Research Datalink population from 2007-2022.

Improving Health-Related Quality of Life in Hepatocellular Carcinoma Patients: Key Methodologies for Assessing Patient Reported Outcomes and Intervention Targets.

Hepatocellular carcinoma (HCC) is a complex cancer that generally arises in the context of cirrhosis. Patients with HCC have symptom burden and impact on health-related quality of life (HRQOL) resulting from underlying liver disease, HCC, and cancer treatments. Patient-reported outcome (PRO) measures may improve the management of patients with HCC by accurately capturing the patient perspective, informing prognosis, guiding treatment decisions, and supporting symptom based and palliative care.

Neuroepidemiology of transverse myelitis and its etiologies in Latin America: A systematic review and meta-analysis.

Background And Objectives: Transverse myelitis (TM) is a rare neuro-inflammatory condition of the spinal cord that can cause chronic and debilitating symptoms reducing quality of life. TM is understudied in developing regions worldwide, particularly in Latin America and the Caribbean (LAC), where the prevalence of TM is unknown. Etiologies of TM are variable, but certain infectious, autoimmune or nutritional abnormalities may be more common in LAC with differing estimated prevalences of these etiologies.

Opportunities and Challenges in Using Electronic Health Record Systems to Study Postacute Sequelae of SARS-CoV-2 Infection: Insights From the NIH RECOVER Initiative.

The benefits and challenges of electronic health records (EHRs) as data sources for clinical and epidemiologic research have been well described. However, several factors are important to consider when using EHR data to study novel, emerging, and multifaceted conditions such as postacute sequelae of SARS-CoV-2 infection or long COVID. In this article, we present opportunities and challenges of using EHR data to improve our understanding of long COVID, based on lessons learned from the National Institutes of Health (NIH)-funded RECOVER (REsearching COVID to Enhance Recovery) Initiative, and suggest steps to maximize the usefulness of EHR data when performing long COVID research.

Machine learning enhanced immunologic risk assessments for solid organ transplantation.

The purpose of this study was to enhance the prediction of solid-organ recipient and donor crossmatch compatibility by applying machine learning (ML). Prediction of crossmatch compatibility is complex and requires an understanding of the recipient and donor human leukocyte antigen (HLA) alleles and recipient HLA antibodies. An HLA allele imputation system that converts HLA antigens to alleles was developed to enhance the prediction's performance.

Emergence of Infective Endocarditis Due to spp.: Results of a Multicenter Cohort.

Background: Infective endocarditis due to spp. (S-IE) has historically been considered a rare entity. Typically linked to injection drug use (IDU), S-IE appears to be a growing problem as the harms of unsafe drug use proliferate.

Virtual library docking for cannabinoid-1 receptor agonists with reduced side effects.

Virtual library docking can reveal unexpected chemotypes that complement the structures of biological targets. Seeking agonists for the cannabinoid-1 receptor (CB1R), we dock 74 million tangible molecules and prioritize 46 high ranking ones for de novo synthesis and testing. Nine are active by radioligand competition, a 20% hit-rate.

White matter microstructure in school-age children with down syndrome.

Down syndrome (DS) is the most common genetic cause of intellectual disability, but our understanding of white matter microstructure in children with DS remains limited. Previous studies have reported reductions in white matter integrity, but nearly all studies to date have been conducted in adults or relied solely on diffusion tensor imaging (DTI), which lacks the ability to disentangle underlying properties of white matter organization. This study examined white matter microstructural differences in 7- to 12-year-old children with DS (n = 23), autism (n = 27), and typical development (n = 50) using DTI as well as High Angular Resolution Diffusion Imaging, and Neurite Orientation and Dispersion Imaging.

A Preliminary Usability Evaluation of an Artificial Intelligence-based, motion-detecting Wearable device: the Geriatric Functional Assessment System.

Background: Physical function is a key determinant of independence among older adults. Yet, there are barriers to assessing physical function in clinic. We developed a wearable geriatric functional assessment system (GFAS) that quickly and effortlessly evaluates physical function.

Comparison of Infants Discharged from Birth Hospitalization with Gastrostomy versus Nasogastric Feeding Tube.

Objective: Many infants, particularly those born premature or with medical complexity, require supplemental enteral nutrition upon discharge from birth hospitalization. Recent literature supports the safety of discharging infants with nasogastric tube (NG) feeding. However, further evidence is needed to characterize populations suited for home NG feeding compared to gastrostomy tube (GT) placement.

Ongoing Symptoms After Acute SARS-CoV-2 or Influenza Infection in a Case-Ascertained Household Transmission Study: 7 US Sites, 2021-2023.

Background: The prevalence and risk factors for ongoing symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [SCV2]) or influenza infection are not well characterized. We conducted a prospective cohort study of households wherein ≥1 individual was infected with SCV2 or influenza to evaluate prevalence of and factors associated with ongoing symptoms at 90 days.

Methods: Index cases and their household contacts provided baseline health and sociodemographic information and collected daily respiratory specimens for 10 days following enrollment.

Broadening the scope and utility of the triple advancement flap in Mohs surgery.

The triple advancement flap has traditionally been used on the trunk, but gained popularity for facial defects of the neck and temple. Advantages of this closure technique include evenly dispersed tension vectors, less need for extensive subcutaneous undermining and mobilization compared to standard facial reconstruction techniques. The nasal sidewall, root, and bridge often pose reconstructive challenges, with convergence of competing tension lines and surrounding anatomic landmarks.

Association between perceived discrimination and pulse wave velocity: a scoping review.

Unlabelled: Racial discrimination is a chronic stressor that may contribute to cardiovascular disease (CVD) disparities in non-Hispanic Black (NHB) adults. NHB adults experience greater perceived discrimination (PD) and CVD risk compared with non-Hispanic White adults. Although the association between PD and some subclinical CVD markers has been examined, the relationship between PD and arterial stiffness has not been established, limiting our understanding of the impact of PD on CVD.

Usefulness of lumbar puncture educational videos for older people with HIV.

Background: Video-based education offers opportunities to enhance patients' medical literacy and to reduce anxiety and hesitation for patients undergoing diagnostic procedures such as lumbar puncture (LP). Multiple studies centered on LP education have demonstrated that video-based education can reduce anxiety regarding possible adverse events, while increasing literacy regarding the procedure itself for clinical purposes. Our study sought to assess the impact of video-based education on knowledge of and willingness to undergo an LP among older people with HIV (PWH).

Using Mindfulness to Manage Moral Injury in Veterans: Feasibility and Satisfaction of a Pilot Randomized Controlled Trial.

Objective: The present study assessed program feasibility and satisfaction among recent-era veterans who participated in Mindfulness to Manage Moral Injury (MMMI), a live facilitated web-based 7-week mindfulness-based program targeting moral injury among veterans.

Method: In total, 56 post-9/11 veterans were recruited with 28 randomized to the MMMI condition and 28 to the Education and Support (ES) condition. Most participants identified as being White (71.

Medicaid Spending and Health-Related Social Needs in the North Carolina Healthy Opportunities Pilots Program.

Importance: Health-related social needs are drivers of worse health and high health care spending. In North Carolina Medicaid's 1115 waiver, the Healthy Opportunities Pilots (HOP) program allows for nonmedical services to address health-related social needs, such as healthy food boxes and housing navigation, financed by Medicaid, in 3 regions of North Carolina.

Objective: To determine whether individual participation in the HOP program is associated with lower Medicaid spending.

Influence of Psychological Safety and Safety Climate Perceptions on Nurses' Infection Prevention and Occupational Safety Practices and Environment.

: The aim of this study was to describe and examine the relationships among elements of infection prevention practices, the care environment, psychological safety, and safety climate in adult medical surgical units in the wake of the COVID-19 pandemic. : Nurses in adult inpatient medical surgical units in the northeast were surveyed electronically. Each self-rated their infection prevention practices and elements of the care environment in their primary work unit.

Potent and selective SETDB1 covalent negative allosteric modulator reduces methyltransferase activity in cells.

A promising drug target, SETDB1, is a dual methyl-lysine (Kme) reader and methyltransferase implicated in cancer and neurodegenerative disease progression. To help understand the role of the triple Tudor domain (3TD) of SETDB1, its Kme reader, we first identify a low micromolar potency small molecule ligand, UNC6535, which occupies simultaneously both the TD2 and TD3 reader binding sites. Further optimization leads to the discovery of UNC10013, a covalent 3TD ligand targeting Cys385 of SETDB1.

The effects of estradiol on subcortical brain volumes in perimenopausal-onset depression.

Background: Perimenopause is associated with increases in depressive and vasomotor symptoms (VMS), which can be alleviated with transdermal estradiol (TE2) administration. Subcortical brain regions are commonly implicated in depression, are dense with E2 receptors and are susceptible to volumetric changes resulting from E2 regulation of synaptic density. No studies have examined linkages among TE2 administration, perimenopausal-onset major depression (PO-MDD) and subcortical brain volumes.

Medical uncertainty in the shadow of Dobbs: Treating obstetric complications in a new reproductive frontier.

Recent changes to United States medical practice following the U.S. Supreme Court's decision in Dobbs v Jackson Woman's Health Organization have led to new forms of medical uncertainty arising from the interpretation and implementation of state law.

Biomolecular condensation of human IDRs initiates endogenous transcription via intrachromosomal looping or high-density promoter localization.

Protein intrinsically disordered regions (IDRs) are critical gene-regulatory components and aberrant fusions between IDRs and DNA-binding/chromatin-associating domains cause diverse human cancers. Despite this importance, how IDRs influence gene expression, and how aberrant IDR fusion proteins provoke oncogenesis, remains incompletely understood. Here we develop a series of synthetic dCas9-IDR fusions to establish that locus-specific recruitment of IDRs can be sufficient to stimulate endogenous gene expression.

Transportation Barriers and Diabetes Outcomes: A Longitudinal Analysis.

Objective: To estimate associations between transportation barriers and diabetes outcomes.

Methods: Longitudinal cohort study; 86 977 adults with type 2 diabetes mellitus in community-based health centers were assessed for transportation barriers, with up to 36 months of follow-up after initial assessment. We compared scenarios in which individuals did not experience transportation barriers to scenarios in which they did, to estimate differences in mean hemoglobin a1c (HbA1c), systolic and diastolic blood pressure (SBP and DBP), and LDL cholesterol.

Shouldice Versus TAPP for Inguinal Hernia Repair: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction: Inguinal hernia (IH) repair is one of the most common surgical procedures worldwide. Among the various techniques available, the Shouldice (SHD) technique is mainly used for nonmesh open repair whereas, the transabdominal preperitoneal (TAPP) approach is a commonly performed minimally invasive method. Despite its widespread use, a direct comparison between the two techniques is lacking.