Increased cholesterol synthesis drives neurotoxicity in patient stem cell-derived model of multiple sclerosis.

Senescent neural progenitor cells have been identified in brain lesions of people with progressive multiple sclerosis (PMS). However, their role in disease pathobiology and contribution to the lesion environment remains unclear. By establishing directly induced neural stem/progenitor cell (iNSC) lines from PMS patient fibroblasts, we studied their senescent phenotype in vitro.

Growth and Symmetry of the Levator Veli Palatini Muscle Within the First Two Years of Life.

Objective: To quantify differences in levator veli palatini (LVP) muscle dimensions based on age, sex, and race and determine the typical range of asymmetry between the left and right sides of the LVP under age 2.

Design: Retrospective cohort study.

Setting: Children's tertiary care hospital.

Effect of Prednisone Dosing on Mineralocorticoid-Related Side Effects With Abiraterone in Prostate Cancer.

Purpose: Abiraterone use for prostate cancer can cause mineralocorticoid excess syndrome (MES; eg, hypertension and hypokalemia). Prednisone mitigates these effects; however, the optimal dose level is unclear. This study examines MES effects from abiraterone with 5 mg of prednisone once daily versus 5 mg twice daily.

Proteomic Analysis Uncovers Multiprotein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus.

Key Points: Proteomics analyses identified seven proteins predictive of time to development of albuminuria among youth with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth cohort, 118 proteins predictive of time to development of hyperfiltration, and three proteins predictive of time to rapid eGFR decline. Seven proteins were predictive of all three outcomes (SEM4A, PSB3, dihydroxyphenylalanine decarboxylase, C1RL1, T132A, pyruvate carboxylase, and C1-esterase inhibitor) and have been implicated in immune regulatory mechanisms, metabolic dysregulation, proteostasis, and cellular signaling pathways. Elastic net Cox proportional hazards model identified distinct multiprotein signatures (38–68 proteins) of time to albuminuria, hyperfiltration, and rapid eGFR decline with concordance for models with clinical covariates and selected proteins between 0.

Nursing Home Palliative Care Referral Process, Barriers, and Proposed Solutions: A Qualitative Study.

Despite evidence that specialized care for seriously ill nursing home (NH) residents is needed, barriers to accessing palliative care (PC) remain. A significant issue is the complexity of the referral process that inhibits timely and equitable access to care. This qualitative descriptive study explored the PC referral process in NHs.

Mortality and Associated Risk Factors Among People Living With HIV With Kaposi Sarcoma: A5263/AMC066 and A5264/AMC067.

Background: AIDS-related Kaposi sarcoma (AIDS-KS) remains a leading cause of morbidity and mortality among people living with HIV in Africa. Mortality among people with AIDS-KS on antiretroviral therapy remains high compared with people on antiretroviral therapy who do not have AIDS-KS.

Setting: People living with HIV with Kaposi sarcoma (KS) who participated in 2 randomized trials (A5263/AMC066 [advanced stage] and A5264/AMC067 [mild-to-moderate stage]) conducted by AIDS Clinical Trials Group/AIDS Malignancy Consortium in low- and middle-income countries.

Adverse childhood experiences predict anxiety during postpartum and early childhood parenting.

Perinatal anxiety disorders (PAD) affect one in five pregnant/postpartum people and are associated with adverse maternal and child health outcomes. Effective treatment and prevention rely on early identification and management of risk factors. Our study fills a gap in literature about how maternal adverse childhood experiences (ACEs) relate to PAD during and beyond the postpartum period.

FMNL1 and mDia1 promote efficient T cell migration through complex environments via distinct mechanisms.

Lymphocyte trafficking and migration through tissues is critical for adaptive immune function and, to perform their roles, T cells must be able to navigate through diverse tissue environments that present a range of mechanical challenges. T cells predominantly express two members of the formin family of actin effectors, Formin-like 1 (FMNL1) and mammalian diaphanous-related formin 1 (mDia1). While both FMNL1 and mDia1 have been studied individually, they have not been directly compared to determine functional differences in promoting T cell migration.

Calorie restriction during gestation impacts maternal and offspring fecal microbiome in mice.

Background: Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood.

Cribriform Plate Foramina Count in Patients With Acquired and Congenital Anosmia.

Background: Cribriform foramina provide the openings for olfactory nerve fibers to cross from the nasal cavity to the olfactory bulb. Disruption of the olfactory nerve fibers is known to affect olfactory function, but little is known about the potential effects on the number of cribriform foramina in congenital anosmia.

Objective: This pilot study aimed to investigate whether there was a reduction in foramina in patients with acquired and congenital anosmia (including both Kallmann syndrome and isolated congenital anosmia) compared to controls with normal olfactory function.

Etiology and Outcomes of Acute Infectious Conjunctivitis in Children.

Objective: To determine the causes of conjunctivitis and whether clinical presentations and outcomes differ by pathogen.

Study Design: This multicenter, case-control study enrolled 390 children (194 cases, 196 controls) whose conjunctival samples were tested for bacterial and viral pathogens. Caregivers completed surveys tracking symptoms, antibiotic use, school attendance, and adverse events.

Early diagnosis of Duchenne muscular dystrophy - A Treat-NMD international workshop.

The diagnosis of Duchenne muscular dystrophy (DMD) is significant at any stage, however an early diagnosis in a presymptomatic or very early phase of DMD, offers unique opportunities and challenges for families and health care providers. Currently, there is limited evidence as to the optimal models of care during this stage of the condition..

DA-R-EPOCH May Mitigate the Adverse Prognostic Implication of the Diagnosis-to-Treatment Interval (DTI) in Large B-Cell Lymphomas.

Background: Short diagnosis-to-treatment interval (DTI) is associated with high-risk disease and poor survival in diffuse large B-cell lymphoma (DLBCL). There is a paucity of literature on DTI and survival in DLBCL treated with first-line DA-R-EPOCH. We hypothesized that rapid initiation of DA-R-EPOCH in aggressive and high-risk DLBCL mitigates the adverse prognostic implication of short DTI.

Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis.

Background: Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years.

The potential mediating role of the gut microbiome and metabolites in the association between PFAS and kidney function in young adults: A proof-of-concept study.

Background: Chronic kidney disease (CKD) affects over 10 % of the global population and can lead to kidney failure and death. Exposure to per- and polyfluoroalkyl substances (PFAS) is associated with increased risk of CKD, yet studies examining the mechanisms linking PFAS and kidney function are lacking. In this exploratory study, we examined longitudinal associations of PFAS exposure with kidney function, and tested if associations were mediated by altered gut bacterial taxa or plasma metabolites using a multi-omics mediation analysis.

The assessment, interpretation and implementation of lung ultrasound examinations in Heart Failure: Current evidence and gaps in knowledge.

Lung ultrasound (LUS) is a simple, fast and non-invasive tool for pulmonary congestion assessment with higher accuracy for the detection of acute heart failure (HF) compared to clinical examination and chest radiography. The integrated assessment with other ultrasound and echocardiographic parameters can lead to a better systemic and pulmonary congestion characterization. Additionally, the combination of echocardiographic and pulmonary features can identify patients at higher risk for adverse outcomes, potentially facilitating both acute and chronic HF management and prognostic stratification.

Lymph Node Sampling in Pediatric Renal Tumors: Survey of Current Practices and Impact of Education.

Objective: To characterize how often and to what extent surgeons are willing to perform retroperitoneal node sampling (RPLNS) for a unilateral renal tumor, and whether they would be encouraged to change goal number of LNs after "targeted education" (TE) METHODS: A survey with selected demographic and LN sampling practice questions was distributed to practicing members of the Society of Pediatric Urology (SPU). After answering a 7-question questionnaire, participants were provided with an abstract on the adequacy of LN yield for staging. This served as the TE and then participants were asked to answer a final question on LN sampling goals.

Implementation of a bundle to improve diagnosis in hospitalized patients: lessons learned.

Objectives: The inpatient setting is a challenging clinical environment where systems and situational factors predispose clinicians to making diagnostic errors. Environmental complexities limit trialing of interventions to improve diagnostic error in active inpatient clinical settings. Informed by prior work, we piloted a multi-component intervention designed to reduce diagnostic error to understand its feasibility and uptake.