Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial.

Background And Aims: An expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity-the waist-to-height ratio (WHtR)-focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.

Methods: The PARAGON-HF trial randomized 4796 patients with heart failure and ejection fraction ≥45% to valsartan or sacubitril/valsartan.

Efficacy and Safety of Mechanical Thrombectomy in Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients on Low-Dose Aspirin.

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

The diagnostic accuracy and feasibility of paediatric visual field tests: A systematic review.

Purpose: Alternative non-standard paediatric visual field (VF) tests have been developed to address the challenges associated with standard approaches. However, diagnostic accuracy of these new VF tests has not yet been rigorously evaluated. This systematic review aims to explore diagnostic accuracy and feasibility of non-standard VF tests in paediatric patients.

Family Connections: The Impact of an Education Program for Carers of Individuals With Borderline Personality Disorder in Italian Mental Health Services.

Borderline personality disorder (BPD) has a strong impact not only on patients' lives but also on their families. The presence of an invalidating environment is one of the key factors in the etiology of BPD. This study evaluated the impact of the Family connections (FC) program on burden, grief, and other clinical variables in 202 caregivers and identified the profiles of participants who improved/deteriorated their levels of burden and grief.

Model construction and clinical therapeutic potential of engineered cardiac organoids for cardiovascular diseases.

Cardiovascular diseases cause significant morbidity and mortality worldwide. Engineered cardiac organoids are being developed and used to replicate cardiac tissues supporting cardiac morphogenesis and development. These organoids have applications in drug screening, cardiac disease models and regenerative medicine.

The Effect of Nirmatrelvir-Ritonavir on Short- and Long-term Adverse Outcomes From COVID-19 Among Patients With Kidney Disease: A Propensity Score-Matched Study.

Background: Patients with kidney disease are at high risk for adverse outcomes after coronavirus disease 2019 (COVID-19) despite vaccination. Because patients with advanced chronic kidney disease (CKD) and kidney failure were excluded from registrational trials, the impact of the protease inhibitor nirmatrelvir-ritonavir in patients with kidney disease is unknown.

Methods: This was a cohort study evaluating adverse outcomes in patients with kidney disease who developed COVID-19.

Flow-based In Vivo Method to Enumerate Translating Ribosomes and Translation Elongation Rate.

Protein synthesis is by far the most energetically costly cellular process in rapidly dividing cells. Quantifying translating ribosomes in individual cells and their average mRNA transit rate is arduous. Quantitating assembled ribosomes in individual cells requires electron microscopy and does not indicate ribosome translation status.

Analytical Validation of Wrist-Worn Accelerometer-Based Step-Count Methods during Structured and Free-Living Activities.

Introduction: Wrist-worn accelerometers can capture stepping behavior passively, continuously, and remotely. Methods utilizing peak detection, threshold crossing, and frequency analysis have been used to detect steps from wrist-worn accelerometer data, but it remains unclear how different approaches perform across a range of walking speeds and free-living activities. In this study, we evaluated the performance of four open-source methods for deriving step counts from wrist-worn accelerometry data, when applied to data from a range of structured locomotion and free-living activities.

What role does wealth play in the racial health gap in the United States? Examining differences among African Americans, Latinos, and non-Hispanic Whites.

Wealth resources has received little attention when studying how socioeconomic status shapes health outcomes. In the United States (USA), there is a growing body of evidence acknowledging a widening racial/ethnic wealth gap. However, little is known about wealth's role in shaping health inequity.

A Scoping Review of Pakistani Healthcare Simulation: Insights for Lower-Middle-Income Countries.

Healthcare simulation has gained global recognition in health professions education, yet its adoption in Pakistan, a lower-middle-income country (LMIC), remains limited. This scoping review aimed to explore how simulation is integrated into healthcare education in Pakistan, highlighting challenges and opportunities to inform similar LMICs. Pakistan serves as a critical case study for LMICs due to its unique challenges, including uneven access to simulation technologies and limited faculty training, which are shared by many similar resource-constrained settings.

The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.

An overview is provided of the evolution of strategies towards xenotransplantation during the past almost 40 years, focusing on advances in gene-editing of the organ-source pigs, pre-transplant treatment of the recipient, immunosuppressive protocols, and adjunctive therapy. Despite initial challenges, including hyperacute rejection resulting from natural (preformed) antibody binding and complement activation, significant progress has been made through gene editing of the organ-source pigs and refinement of immunosuppressive regimens. Major steps were the identification and deletion of expression of the three known glycan xenoantigens on pig vascular endothelial cells, the transgenic expression of human "protective" proteins, e.

Drought as an emergent driver of ecological transformation in the twenty-first century.

Under climate change, ecosystems are experiencing novel drought regimes, often in combination with stressors that reduce resilience and amplify drought's impacts. Consequently, drought appears increasingly likely to push systems beyond important physiological and ecological thresholds, resulting in substantial changes in ecosystem characteristics persisting long after drought ends (i.e.

Uncovering somatic mosaic variants of -related overgrowth disorders - three cases with different clinical presentations.

Introduction: related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spectrum of overgrowth and vascular malformations affecting various body regions.

Methods: Conventional diagnostic methods struggle to detect and confirm pathogenic PIK3CA gene variants due to the mosaic nature of these disorders and the limited accessibility of affected tissues.

Storm Surge Projection and Objective-Based Risk Management for Climate Change Adaptation along the US Atlantic Coast.

Climate change brings intense hurricanes and storm surges to the US Atlantic coast. These disruptive meteorological events, combined with sea level rise (SLR), inundate coastal areas and adversely impact infrastructure and environmental assets. Thus, storm surge projection and associated risk quantification are needed in coastal adaptation planning and emergency management.

Case report of recurrent vasa previa.

Introduction: Vasa previa is a complication of pregnancy, which affects approximately 1:1200 pregnancies, and when undiagnosed prenatally, it can be associated with significant perinatal mortality. This condition is thought to be a sporadic entity without known genetic or familial associations and thus considered to carry a negligible recurrence risk.

Key Findings: We present a case of a 42-year-old gravida 3 para 2 diagnosed on transvaginal ultrasound with a vasa previa at 34 weeks associated with vaginal bleeding, which required an urgent caesarean in a prior spontaneous pregnancy.

Applications of Cell-Based Protein Array Technology to Preclinical Safety Assessment of Biological Products.

Off-target evaluation is essential in preclinical safety assessments of novel biotherapeutics, supporting lead molecule selection, endpoint selection in toxicology studies, and regulatory requirements for first-in-human trials. Off-target interaction of a therapeutic antibody and antibody derivatives has been historically assessed via the Tissue Cross-Reactivity (TCR) study, in which the candidate molecule is used as a reagent in immunohistochemistry (IHC) to assess binding of the candidate molecule to a panel of human tissue sections. The TCR approach is limited by the performance of the therapeutic as an IHC reagent, which is often suboptimal to outright infeasible.

Inpp5e Is Critical for Photoreceptor Outer Segment Maintenance.

In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouse Inpp5e where the gene was deleted either during outer segment formation or after outer segments were fully formed.

Regio-Selective Mechanical Enhancement of Polymer-Grafted Nanoparticle Composites via Light-Mediated Crosslinking.

Polymer-brush-grafted nanoparticles (PGNPs) that can be covalently crosslinked post-processing enable the fabrication of mechanically robust and chemically stable polymer nanocomposites with high inorganic filler content. Modifying PGNP brushes to append UV-activated crosslinkers along the polymer chains would permit a modular crosslinking strategy applicable to a diverse range of nanocomposite compositions. Further, light-activated crosslinking reactions enable spatial control of crosslink density to program intentionally inhomogeneous mechanical responses.

A prospective study of diagnostic testing and hospital charges after brief resolved unexplained event.

Objectives: To evaluate diagnostic testing frequency/yield and determine drivers of hospital charges in a prospective cohort of infants with brief resolved unexplained event (BRUE) to test the hypothesis that length of stay (LOS), low-yield diagnostic testing, and repeat hospital visits increase costs.

Methods: We conducted a prospective cohort study of infants admitted after BRUE to determine how clinical practice impacts the cost of care. Charge data from our institution's billing records database included room and board, diagnostics, medications, and professional fees for index hospitalizations and 6-month follow-ups.

Durable suppression of seizures in a preclinical model of KCNT1 genetic epilepsy with divalent small interfering RNA.

Objective: Gain-of-function variants in the KCNT1 gene, which encodes a sodium-activated potassium ion channel, drive severe early onset developmental epileptic encephalopathies including epilepsy of infancy with migrating focal seizures and sleep-related hypermotor epilepsy. No therapy provides more than sporadic or incremental improvement. Here, we report suppression of seizures in a genetic mouse model of KCNT1 epilepsy by reducing Kcnt1 transcript with divalent small interfering RNA (siRNA), an emerging variant of oligonucleotide technology developed for the central nervous system.

Parental Style, Grandchild Problematic Behaviors, and Parental Role Demands Among Grandparent Caregivers.

The present study evaluates the impact of grandchild distress on parental competence as mediated by Baumrind's parental styles in a sample of 238 custodial grandparents ( age = 58.06). AMOS structural equation findings yielded a model which indicated that both the Laissez-Faire and Authoritarian styles each predicted role stress and/or parental efficacy.

Extracting Housing and Food Insecurity Information From Clinical Notes Using cTAKES.

Objective: To assess the utility and challenges of using natural language processing (NLP) in electronic health records (EHRs) to ascertain health-related social needs (HRSNs) among older adults.

Study Setting And Design: We extracted HRSN information using the NLP system Clinical Text Analysis and Knowledge Extraction System (cTAKES), combined with Concept Unique Identifiers and Systematized Nomenclature for Medicine codes. We validated cTAKES performance, via manual chart review, on two HRSNs: food insecurity, which was included in the healthcare system's HRSN screening tool, and housing insecurity, which was not.

Couple-Based Intervention to Improve HIV Care Engagement for Women and their Partners in KwaZulu-Natal, South Africa: Outcomes of a Pilot Randomized Controlled Trial.

We evaluated a couple-based intervention targeting human immunodeficiency virus (HIV) care needs of women, with the option to support HIV-related needs of male partners. Adult women with HIV adherence difficulties in a monogamous relationship with a male partner for ≥6 months were recruited in KwaZulu-Natal, South Africa. Twenty couples were randomized (1:1) to either START Together, a five-session manualized behavioral intervention, or treatment as usual, adherence counseling referral.

Curvature Memory in Electrically Stimulated Lipid Membranes.

We demonstrate, using non-equilibrium molecular dynamics simulations, that lipid membrane capacitance varies with surface charge accumulation linked to membrane shape and curvature changes. Specifically, we show that lipid membranes exhibit a hysteretic response when exposed to oscillatory electric fields. The electromechanical coupling in these membranes leads to hysteretic buckling, in which the membrane can spontaneously buckle in one of two distinct directions along the electric field, even for the same ionic charge accumulation at the water-membrane interface.

Targeting CRM1 for Progeria Syndrome Therapy.

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by progerin, a mutant variant of lamin A. Progerin anchors aberrantly to the nuclear envelope disrupting a plethora of cellular processes, which in turn elicits senescence. We previously showed that the chromosomal region maintenance 1 (CRM1)-driven nuclear export pathway is abnormally enhanced in patient-derived fibroblasts, due to overexpression of CRM1.