Generation of a human induced pluripotent stem cell line (CRICKi021-A) from a patient with Ullrich congenital muscular dystrophy carrying a pathogenic mutation in the COL6A1 gene.

Ullrich congenital muscular dystrophy (UCMD) represents the most severe subtype of collagen VI-related dystrophies (COL6-RDs), a spectrum of rare extracellular matrix disorders affecting skeletal muscle and connective tissue. Here, we generated an induced pluripotent stem cell (iPSC) line (CRICKi021-A) from a UCMD patient with de novo dominant-negative mutation in COL6A1 gene by reprogramming dermal fibroblasts using a non-integrating mRNA-based protocol. The resulting human iPSCs displayed normal morphology, expressed pluripotency-associated markers and differentiated into the three germ layers.

Generation of TWO iPSC lines (CRICKi009-A; CRICKi010-A) from patients with type 1 von Hippel-Lindau (VHL) and histopathologically confirmed renal cell carcinoma (RCC).

VHL disease is an inherited and autosomal dominant disorder affecting 1 in 36,0000 individuals worldwide. It is caused by von Hippel-Lindau (VHL) gene mutations and can affect both genders and all ethnic backgrounds (Nordstrom-O'Brien et al., 2009; Maher, 2004).

Rapid Access Diagnostics for Asthma (RADicA): protocol for a prospective cohort study to determine the optimum series of investigations to diagnose asthma using conventional and novel tests.

Introduction: The diagnosis of asthma is often based on characteristic patterns of symptoms in the absence of an alternative explanation, resulting in over and under diagnosis. Therefore, diagnostic guidelines usually recommend including confirmation of variable airflow obstruction. Some recommend using a sequence of objective tests; however the tests used, the specific cut-off values and the specified order are yet to be validated.

Exploring the Factors That Impact Recruitment and Retention of Pediatricians in Irish Community Hospitals Through the Attitudes of Trainees and Physicians-in-Practice.

Background: Difficulty attracting physicians to work in rural and remote areas is a worldwide problem. Specific to pediatrics, barriers to recruitment include burdensome on-call rosters, a lack of career opportunities for partners and professional isolation.

Methods: To examine attitudes to working in a community hospital in Ireland, a mixed-methods sequential analysis approach was undertaken.

Asthma diagnosis: a comparison of established diagnostic guidelines in adults with respiratory symptoms.

Background: Considerable variability exists between asthma diagnostic guidelines. We tested the performance characteristics of the European Respiratory Society (ERS), the National Institute for Health and Care Excellence (NICE) and the Global Initiative for Asthma (GINA) guidelines for the diagnosis of asthma in adults.

Methods: In this prospective observational study (ISRCTN-11676160, May 2019-June 2022), participants referred from primary care with clinician-suspected asthma underwent comprehensive investigation including: spirometry, bronchodilator reversibility, fractional exhaled nitric oxide, peak expiratory flow variability, bronchial challenge testing with methacholine and mannitol, and responsiveness to inhaled corticosteroid therapy.

Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity.

Gasdermin-mediated inflammatory cell death (pyroptosis) can activate protective immunity in immunologically cold tumors. Here, we performed a high-throughput screen for compounds that could activate gasdermin D (GSDMD), which is expressed widely in tumors. We identified 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB) as a direct and selective GSDMD agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD.

Use of Interactive Food Labels to Increase Confidence in Preparing Produce among College Students.

College students may have limited access to produce and may lack confidence in preparing it, but cooking videos can show how to make healthy dishes. The Cognitive Theory of Multimedia Learning suggests that learning is enhanced when visual and auditory information is presented considering cognitive load (e.g.

The impact of time of day on the diagnostic performance of tests for asthma.

https://bit.ly/4b79e5J.

Patient Reported Barriers for Participation in Supervised Exercise Therapy for Symptomatic Peripheral Artery Disease.

Background: Supervised exercise therapy (SET) provides clinical benefit for patients suffering from intermittent claudication due to peripheral artery disease (PAD). However, enrollment in programs when offered remains low. We sought to identify patient-reported barriers to enrollment in SET as part of a prospective quality improvement program.

An orthosteric/allosteric bivalent peptide agonist comprising covalently linked protease-activated receptor-derived peptides mimics in vitro and in vivo activities of activated protein C.

Background: Activated protein C (APC) has anticoagulant and cytoprotective cell-signaling activities, which often require protease-activated receptor (PAR) 1 and PAR3 and PAR cleavages at noncanonical sites (R46-N47 and R41-G42, respectively). Some PAR1-derived (P1) peptides and PAR3-derived (P3) peptides, eg, P1-47-66 and P3-42-65, mimic APC's cell signaling. In anti-inflammatory assays, these 2 peptides at low concentrations synergistically attenuate cellular inflammation.

ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D.

Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores after cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT). Here we report that GSDMD Cys191 is S-palmitoylated and that palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS).

What Effect Do Goal Setting Interventions Have on Physical Activity and Psychological Outcomes in Insufficiently Active Adults? A Systematic Review and Meta-Analysis.

Background: Goal setting is commonly used for promoting physical activity (PA) among insufficiently active individuals. Previous reviews have analyzed the effects of goal setting on PA, but the purpose of this systematic review was to examine the concurrent effects of goal setting on PA and psychological outcomes in insufficiently active individuals to support interventions aiming to produce sustained PA behavior change.

Methods: In this review (PROSPERO: CRD42021243970), we identified 13 studies with 1208 insufficiently active adults that reported the effects of goal-setting interventions (range 3-24 wk) on both PA and psychological outcomes (eg, self-efficacy, motivation, and affect).

Determining factors of physical activity and sedentary behaviour in university students during the COVID-19 pandemic: A longitudinal study.

Introduction: Historically, university students demonstrate poor movement behaviours that could negatively impact current and future health. Recent literature has focused on identifying determinants of physical activity (PA) and sedentary behaviour (SB) in this population to inform the development of intervention strategies. However, the COVID-19 pandemic substantially restricted movement behaviours in this population, meaning findings of previous research may no longer be applicable within the current societal context.

Investigation into the use of novel pretreatments in the fermentation of Alaria esculenta by Lactiplantibacillus plantarum and kombucha SCOBY.

High pressure processing (HPP), ultrasound probe (USP) and ultrasound bath (USB) were applied to Alaria esculenta as a fermentation pre-treatment. Seaweed was then fermented by Lactiplantibacillus plantarum (LAB) or symbiotic culture of bacteria and yeast (SCOBY). Physiochemical properties of fermented seaweed were measured.

Motivational profiles and their relation to wellbeing, burnout, and drop-out intentions in university football players in the UK: A mixed methods approach.

In this multi-study paper, we adopted a mixed methods approach to examine the motivational profiles of sub-elite student footballers participating in UK university sport, in relation to their wellbeing, burnout, and drop-out intentions. In Study 1 we used a cross-sectional survey design to collect quantitative measures of motivational regulations, wellbeing, burnout, and drop-out intentions in 260 (n = 129 female) and (n = 131 male) sub-elite university footballers from UK universities (Mage = 20.7 y, SD = 1.

Pharmacodynamics, safety, tolerability and pharmacokinetics of a single oral dose of an engineered phenylalanine ammonia-lyase in patients with phenylketonuria.

The cornerstone treatment of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) is a lifelong low-protein diet with phenylalanine (Phe) free L-amino acid supplements. However, the PKU diet has significant shortcomings, and there is a clinically unmet need for new therapeutics to improve patient outcomes. CDX-6114 is a modified phenylalanine ammonia-lyase (PAL) enzyme obtained by a mutation in the PAL sequence.

Orthogonal Enzyme-Substrate Design Strategy for Discovery of Human Protein Palmitoyltransferase Substrates.

Protein palmitoylation, with more than 5000 substrates, is the most prevalent form of protein lipidation. Palmitoylated proteins participate in almost all areas of cellular physiology and have been linked to several human diseases. Twenty-three zDHHC enzymes catalyze protein palmitoylation with extensive overlap among the substrates of each zDHHC member.

Cross-talk between B cells, microglia and macrophages, and implications to central nervous system compartmentalized inflammation and progressive multiple sclerosis.

Background: B cells can be enriched within meningeal immune-cell aggregates of multiple sclerosis (MS) patients, adjacent to subpial cortical demyelinating lesions now recognized as important contributors to progressive disease. This subpial demyelination is notable for a 'surface-in' gradient of neuronal loss and microglial activation, potentially reflecting the effects of soluble factors secreted into the CSF. We previously demonstrated that MS B-cell secreted products are toxic to oligodendrocytes and neurons.

MerTK is a mediator of alpha-synuclein fibril uptake by human microglia.

Mer tyrosine kinase (MerTK) is a receptor tyrosine kinase that mediates non-inflammatory, homeostatic phagocytosis of diverse types of cellular debris. Highly expressed on the surface of microglial cells, MerTK is of importance in brain development, homeostasis, plasticity and disease. Yet, involvement of this receptor in the clearance of protein aggregates that accumulate with ageing and in neurodegenerative diseases has yet to be defined.