Glycogen synthase GYS1 overactivation contributes to glycogen insolubility and malto-oligoglucan-associated neurodegenerative disease.

Polyglucosans are glycogen molecules with overlong chains, which are hyperphosphorylated in the neurodegenerative Lafora disease (LD). Brain polyglucosan bodies (PBs) cause fatal neurodegenerative diseases including Lafora disease and adult polyglucosan body disease (ABPD), for which treatments, biomarkers, and good understanding of their pathogenesis are currently missing. Mutations in the genes for the phosphatase laforin or the E3 ubiquitin ligase malin can cause LD.

Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a valid, highly utilized measure for assessing ADL impacts in patients with Friedreich ataxia. We provide evidence of the psychometric validity of the FARS-ADL in two cohorts of patients with spinocerebellar ataxia (SCA).

Methods: Using data from a cohort of real-world subjects with SCA (recruited at Massachusetts General Hospital [MGH]; n = 33) and a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), comprising a subset of patients with the SCA3 genotype (n = 89), the psychometric measurement properties and minimal change thresholds of the FARS-ADL were examined.

Implementation and evaluation of a novel community-based urban mobile health clinic in Toronto, Ontario.

Setting: Despite Canada's single-payer health system, marginalized populations often experience poor health outcomes and barriers to healthcare access. In response, mobile health clinics (MHCs) have been deployed in several cities across Canada. MHCs are well established in the United States; however, little is known about their role and impact in a country with universal healthcare.

Ribosomal A-site interactions with near-cognate tRNAs drive stop codon readthrough.

Transfer RNAs (tRNAs) serve as a dictionary for the ribosome translating the genetic message from mRNA into a polypeptide chain. In addition to this canonical role, tRNAs are involved in other processes such as programmed stop codon readthrough (SC-RT). There, tRNAs with near-cognate anticodons to stop codons must outcompete release factors and incorporate into the ribosomal decoding center to prevent termination and allow translation to continue.

The birth of the virtual clinic: welcome to the Mediverse.

The COVID-19 pandemic triggered a global pivot to virtual care (VC) technologies. While there has been considerable academic work exploring the "how" of VC, few studies have explored the impact of this pivot, its unintended consequences, and its governing rationales. This study addresses this gap in relation to care, professional identity and the evolving requirements for health professions education.

High throughput method for simultaneous screening of membrane permeability and toxicity for discovery of new cryoprotective agents.

Cryoprotective agent (CPA) toxicity is the most limiting factor impeding cryopreservation of critically needed tissues and organs for transplantation and medical research. This limitation is in part due to the challenge of rapidly screening compounds to identify candidate molecules that are highly membrane permeable and non-toxic at high concentrations. Such a combination would facilitate rapid CPA permeation throughout the sample, enabling ice-free cryopreservation with minimal toxicity.

Regulation of stress granule maturation and dynamics by poly(ADP-ribose) interaction with PARP13.

Non-covalent interactions of poly(ADP-ribose) (PAR) facilitate condensate formation, yet the impact of these interactions on condensate properties remains unclear. Here, we demonstrate that PAR-mediated interactions through PARP13, specifically the PARP13.2 isoform, are essential for modulating the dynamics of stress granules-a class of cytoplasmic condensates that form upon stress, including types frequently observed in cancers.

Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing.

Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling.

Metal-rich lacustrine sediments from legacy mining perpetuate copper exposure to aquatic-riparian food webs.

Historic copper mining left a legacy of metal-rich tailings resulting in ecological impacts along and within Torch Lake, an area of concern in the Keweenaw Peninsula, Michigan, USA. Given the toxicity of copper to invertebrates, this study assessed the influence of this legacy on present day nearshore aquatic and terrestrial ecosystems. We measured the metal (Co, Cu, Ni, Zn, Cd) and metalloid (As) concentrations in sediment, pore water, surface water, larval and adult insects, and two riparian spider taxa collected from Torch Lake and a nearby reference lake.

Evaluation of an AI-Based Voice Biomarker Tool to Detect Signals Consistent With Moderate to Severe Depression.

Purpose: Mental health screening is recommended by the US Preventive Services Task Force for all patients in areas where treatment options are available. Still, it is estimated that only 4% of primary care patients are screened for depression. The goal of this study was to evaluate the efficacy of machine learning technology (Kintsugi Voice, v1, Kintsugi Mindful Wellness, Inc) to detect and analyze voice biomarkers consistent with moderate to severe depression, potentially allowing for greater compliance with this critical primary care public health need.

AGEing of collagen: The effects of glycation on collagen's stability, mechanics and assembly.

Advanced Glycation End Products (AGEs) are the end result of the irreversible, non-enzymatic glycation of proteins by reducing sugars. These chemical modifications accumulate with age and have been associated with various age-related and diabetic complications. AGEs predominantly accumulate on proteins with slow turnover rates, of which collagen is a prime example.

Validity of the Diabetic Wound Assessment Learning Tool.

Purpose: The development of the Diabetic Wound Assessment Learning Tool (DiWALT) has previously been described. However, an examination of its application to a larger, more heterogeneous group of participants is lacking. In order to allow for a more robust assessment of the psychometric properties of the DiWALT, we applied it to a broader group of participants.

Healthy Kai (Food) Checker Web-Based Tool to Support Healthy Food Policy Implementation: Development and Usability Study.

Background: Public health programs and policies can positively influence food environments. In 2016, a voluntary National Healthy Food and Drink Policy was released in New Zealand to improve the healthiness of food and drinks for hospital staff and visitors. However, no resources were developed to support policy implementation.

Does Body Postural Configuration Affect Upper Limb Performance During Point-to-Point Hand Movements?

Adopting a postural configuration may be regarded as preparation for the performance of an upcoming movement. However, it is unclear how different postural configurations affect motor performance. The aim of the current study was to examine how body posture - sitting versus standing - influences fast and accurate planar point-to-point hand movements.

Impact of workflow times on successful reperfusion after endovascular treatment in the late time window.

Background And Purpose: Successful and complete reperfusion should be the aim of every endovascular thrombectomy (EVT) procedure. However, the effect of time delays on successful reperfusion in late window stroke patients presenting 6-to-24 h from onset has not been investigated.

Materials And Methods: We pooled individual patient-level data from seven trials and registries for anterior circulation stroke patients treated with EVT between 6 and 24 h from onset.

'I Don't Think I Have Ever Worked Harder on a Case': Needs of Canadian Child Protection Workers and Parents With Intellectual Disabilities.

Background: The current literature has established that prejudice in child protection cases with parents with intellectual disabilities continues to persist. However, complexities of these cases are not well-understood from the perspective of child protection workers. This study aimed to identify the needs of child protection workers and their views on factors that influence supports for parents with intellectual disabilities.

Distinct computational mechanisms of uncertainty processing explain opposing exploratory behaviors in anxiety and apathy.

Background: Decision-making in uncertain environments can lead to varied outcomes, and how we process those outcomes may depend on our emotional state. Understanding how individuals interpret the sources of uncertainty is crucial for understanding adaptive behavior and mental well-being. Uncertainty can be broadly categorized into two components: volatility and stochasticity.

Mepolizumab real-world effectiveness in severe asthma with an eosinophilic phenotype and overlapping severe allergic asthma.

Background: Some patients with severe asthma have overlapping allergic and eosinophilic phenotypes and may be eligible for anti-eosinophilic or anti-IgE biologics.

Objective: This post hoc sub-analysis assessed real-world mepolizumab effectiveness in patients with overlapping allergic and eosinophilic phenotypes, using 1-year data from the international, prospective REALITI-A study.

Methods: The clinically significant asthma exacerbation (CSE) rate was assessed 1 year prior to (pre-treatment) and following (follow-up) mepolizumab treatment, stratified by baseline total IgE levels (tIgE; <60, 60-<190, 190-<550, and ≥550 kU/L), atopic status (yes/no/unknown), prior omalizumab use (yes/no), geographic baseline omalizumab eligibility (eligible/non-eligible), and baseline tIgE level and blood eosinophil count (BEC) threshold combinations (<81 or ≥81 kU/L and <300 or ≥300 cells/µL).

Gender identity and activity limitations: A national study on transgender and non-binary Canadians.

Introduction: Activity limitations among transgender and non-binary individuals remain largely unexplored using population-based samples. This study examines the risk of activity limitations across different gender identities in Canada.

Method: Using data from the 2021 Canadian long-form Census, logistic regressions estimated the adjusted odds of reporting activity limitations (seeing, hearing, mobility/dexterity, mental, cognitive, and other) across gender identities.