The role of dystrophin isoforms and interactors in the brain.

Dystrophin is a protein crucial for maintaining the structural integrity of skeletal muscle. So far, the attention was focused on the role of dystrophin in muscle in view of the devastating progression of weakness and early death that characterises Duchenne muscular dystrophy. However, in the last few years, the role of shorter dystrophin isoforms, including development and adult expression-specific mechanisms, has been a greater focus.

Golodirsen restores DMD transcript imbalance in Duchenne Muscular Dystrophy patient muscle cells.

Background: Antisense oligonucleotides (AON) represent a promising treatment for Duchenne muscular dystrophy (DMD) carrying out-of-frame deletions, but also show limitations. In a completed clinical trial golodirsen, approved by FDA to induce skipping of DMD gene exon 53 in eligible patients, we demonstrated increase in DMD expression and protein production, albeit with inter-patient variability.

Methods: Here, we investigate further the golodirsen mechanism of action using myotubes derived from MyoD transfected fibroblasts isolated from DMD patients at the baseline of the clinical trial SRP-4053.

Dementia Care Among United States Dialysis Providers: A Mixed Methods Study Evaluating Clinician Comfort and Knowledge.

Rationale & Objective: Given the high burden of dementia in dialysis patients, the dialysis workforce needs to be prepared to provide high-quality, person-centered dementia care. We explored comfort with and knowledge of dementia among US dialysis care providers.

Study Design: Web-based survey.

Fluorescent tagging of endogenous IRS2 with an auxin-dependent degron to assess dynamic intracellular localization and function.

Insulin Receptor Substrate 2 (IRS2) is a signaling adaptor protein for the insulin (IR) and Insulin-like Growth Factor-1 (IGF-1R) receptors. In breast cancer, IRS2 contributes to both the initiation of primary tumor growth and the establishment of secondary metastases through regulation of cancer stem cell (CSC) function and invasion. However, how IRS2 mediates its diverse functions is not well understood.

Implementation and evaluation of pharmacist-led heart failure diagnostic and guideline directed medication therapies clinic.

Background: Timely diagnosis of heart failure (HF) and rapid optimisation of guideline-directed medication therapy (GDMT) improves patients qualities of life, reducing mortality and morbidity. Previous papers describe the role of pharmacists in medication optimisation, but not in the diagnosis of HF.

Aim: To describe the development, implementation, and evaluation of pharmacist-led heart failure clinics with respect to time from referral to diagnosis, time from diagnosis to first review with a specialist, and the proportion receiving optimal GDMT 180 days after diagnosis.

Synapsin condensation is governed by sequence-encoded molecular grammars.

Multiple biomolecular condensates coexist at the pre- and post- synapse to enable vesicle dynamics and controlled neurotransmitter release in the brain. In pre-synapses, intrinsically disordered regions (IDRs) of synaptic proteins are drivers of condensation that enable clustering of synaptic vesicles (SVs). Using computational analysis, we show that the IDRs of SV proteins feature evolutionarily conserved non-random compositional biases and sequence patterns.

Condensates of synaptic vesicles and synapsin are molecular beacons for actin sequestering and polymerization.

Neuronal communication relies on precisely maintained synaptic vesicle (SV) clusters, which assemble via liquid-liquid phase separation (LLPS). This process requires synapsins, the major synaptic phosphoproteins, which are known to bind actin. The reorganization of SVs, synapsins and actin is a hallmark of synaptic activity, but their interplay is still unclear.

Detecting and monitoring concerns against HPV vaccination on social media using large language models.

Health risks due to preventable infections such as human papillomavirus (HPV) are exacerbated by persistent vaccine hesitancy. Due to limited sample sizes and the time needed to roll out, traditional methodologies like surveys and interviews offer restricted insights into quickly evolving vaccine concerns. Social media platforms can serve as fertile ground for monitoring vaccine-related conversations and detecting emerging concerns in a scalable and dynamic manner.

Acute introduction of phosphoserine-129 α-synuclein induces severe swelling of mitochondria at lamprey synapses.

Abnormal synaptic aggregation of α-synuclein is linked to cognitive deficits in Parkinson's disease (PD). While the impacts of excess α-synuclein on synaptic function are well established, comparatively less is known about the effects on local mitochondria. Here, we examined morphological features of synaptic mitochondria treated with wild type (WT) or phosphoserine 129 (pS129) α-synuclein, a variant with prominent synaptic accumulation in PD.

Expanding Myeloma Training and Care in Western Kenya Through the ECHO Model: The Pilot Phase.

Purpose: Multiple myeloma (MM) in rural western Kenya is characterized by under and late diagnosis with poor long-term outcomes. Inadequate skilled rural health care teams are partly to blame. The Extension for Community Healthcare Outcomes (ECHO) model attempts to bridge this skills gap by linking rural primary/secondary health care teams (spokes) to myeloma experts in a tertiary care center (hub) in a longitudinal training program.

Patient Care Technician Staffing and Outcomes Among US Patients Receiving In-Center Hemodialysis.

Importance: Dialysis patient care technicians (PCTs) play a critical role in US in-center hemodialysis (HD) care, but little is known about the association of PCT staffing with patient outcomes at US HD facilities.

Objective: To estimate the associations of in-center HD patient outcomes with facility-level PCT staffing.

Design, Setting, And Participants: This was a retrospective cohort study, with data analysis performed from March 2023 to January 2024.

Patient Care Technician Staffing in US Hemodialysis Facilities: An Ecological Study.

Rationale & Objective: Technicians caring for patients receiving dialysis play a critical, frontline role in the care of patients receiving dialysis in the United States. We sought to provide a comprehensive description and identify correlates of US in-center hemodialysis facility patient care technician staffing patterns.

Study Design: This was an ecological study.

A Collaborative Approach to Improving Care Outcomes for Residents in Assisted Living.

Assisted Living (AL) residents are embedded in "care convoys" comprised of a dynamic network of formal and informal care partners. Using the model-a multi-level framework connecting care convoy properties to resident outcomes-we examined healthcare management and communication between convoy members. We recommend strategies to engage primary care in supporting collaboration, communication, and consensus-building for older adults and their convoys.

Networking to Optimize exon 53 Skipping in the Brain of Mouse Model.

Duchenne muscular dystrophy (DMD) is caused by mutations in the gene that disrupt the open reading frame and thus prevent production of functional dystrophin proteins. Recent advances in DMD treatment, notably exon skipping and AAV gene therapy, have achieved some success aimed at alleviating the symptoms related to progressive muscle damage. However, they do not address the brain comorbidities associated with DMD, which remains a critical aspect of the disease.

Breast Health Awareness: Understanding Health-Seeking Behavior in Western Kenya.

Introduction: In Kenya, patients with breast cancer predominantly present with late-stage disease and experience poor outcomes. To promote early-stage diagnosis, we implemented the Academic Model Providing Access to Healthcare (AMPATH) Breast and Cervical Cancer Control Program (ABCCCP) in Western Kenya.

Objective: The aim of this study was to assess differences between patients presenting to health facilities and health fairs.

Evolution of pharmacogenomic services and implementation of a multi-state pharmacogenomics clinic across a large rural healthcare system.

Pharmacogenomics (PGx) aims to maximize drug benefits while minimizing risk of toxicity. Although PGx has proven beneficial in many settings, clinical uptake lags. Lack of clinician confidence and limited availability of PGx testing can deter patients from completing PGx testing.

Excess phosphoserine-129 α-synuclein induces synaptic vesicle trafficking and declustering defects at a vertebrate synapse.

α-Synuclein is a presynaptic protein that regulates synaptic vesicle (SV) trafficking. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), α-synuclein aberrantly accumulates throughout neurons, including at synapses. During neuronal activity, α-synuclein is reversibly phosphorylated at serine 129 (pS129).