Prenatal SMN-dependent defects in translation uncover reversible primary cilia phenotypes in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated SMA patients, indicative of alterations in brain development.

Effect of knee joint position on soleus muscle function during isokinetic plantarflexion.

Purpose: Contribution of the gastrocnemii muscles to ankle moment is influenced by the knee joint position because they span the knee and the ankle joint as well. However, limited information is available on the effect of knee joint position on soleus activation under dynamic plantarflexion, hence the aim of this study was to investigate if soleus have a compensatory strategy in fascicle behavior or EMG activity during knee flexed plantarflexion in order to reduce the magnitude of the decrement in ankle moment.

Equipment And Methods: Isokinetic dynamometry with EMG and ultrasound measurements was used to estimate medial gastrocnemius and soleus behavior during knee flexed and extended plantarflexions using three angular velocities.

Neural correlates of Bayesian social belief updating in the medial prefrontal cortex.

Social learning, a hallmark of human behavior, entails integrating other's actions or ideas with one's own. While it can accelerate the learning process by circumventing slow and costly individual trial-and-error learning, its effectiveness depends on knowing when and whose information to use. In this study, we explored how individuals use social information based on their own and others' levels of uncertainty.

Cortical response to transient and long-term visual field loss.

In the visual cortices, receptive fields (RFs) are arranged in a gradient from small sizes in the center of the visual field to the largest sizes at the periphery. Using functional magnetic resonance imaging (fMRI) mapping of population RFs, we investigated RF adaptation in V1, V2, and V3 in patients after long-term photoreceptor degeneration affecting the central (Stargardt disease [STGD]) and peripheral (Retinitis Pigmentosa [RP]) regions of the retina. In controls, we temporarily limited the visual field to the central 10° to model peripheral loss.

Lymphotoxin beta receptor mice display altered B- and T-cell subpopulations in the bone marrow and peritoneal cavity after infection.

Lymphotoxin β receptor (LTβR/TNFRSF3) signaling plays a crucial role in immune defense. Notably, LTβR-deficient (LTβR) mice exhibit severe defects in innate and adaptive immunity against various pathogens and succumb to infection. Here, we investigated the bone marrow (BM) and peritoneal cavity (PerC) compartments of LTβR mice during infection, demonstrating perturbed B-cell and T-cell subpopulations in the absence of LTβR signaling.

Targeting the Epigenetic Remodeler GCN5 Prevents Vascular Oxidative Stress and Endothelial Dysfunction in Obesity: Insights in Patients with Cardiometabolic Disease.

Introduction: Epigenetic changes are important modulators of gene expression. The histone acetyltransferase gene non-derepressible 5 (Gcn5) is emerging as a pivotal epigenetic player in metabolism and cancer, yet its role in obesity and cardiovascular disease remains elusive.

Aims: To investigate Gcn5 role in obesity-related endothelial dysfunction.

Machine learning for myocarditis diagnosis using cardiovascular magnetic resonance: a systematic review, diagnostic test accuracy meta-analysis, and comparison with human physicians.

Myocarditis is an inflammation of heart tissue. Cardiovascular magnetic resonance imaging (CMR) has emerged as an important non-invasive imaging tool for diagnosing myocarditis, however, interpretation remains a challenge for novice physicians. Advancements in machine learning (ML) models have further improved diagnostic accuracy, demonstrating good performance.

Experiences and challenges of implementing clinical medication reviews in daily practice: a mixed-methods study.

Introduction: Organisational problems still prevent widespread implementation of clinical medication reviews. The Opti-Med2 method was developed to facilitate the process of performing clinical medication reviews. The method includes patient involvement by means of a questionnaire and expert teams of community pharmacists and general practitioners (GPs) to perform pharmacotherapeutic analyses, providing the patients' own GP with pharmacotherapeutic advice.

Target controlled infusion in the intensive care unit: a scoping review.

Target-controlled infusion (TCI) systems, originally developed for intravenous drug administration of anesthetic drugs, enable precise drug delivery based on pharmacokinetic-pharmacodynamic (PKPD) models. While widely used in the operating room, their application in the intensive care unit (ICU) remains limited despite the complexity of drug dosing in critically ill patients. This scoping review evaluates existing evidence on the use of TCI systems in ICU settings, focusing on sedation, analgesia, and antibiotic administration.

Hair analysis for monitoring adherence to inhaled respiratory medications: possibilities and limitations.

Purpose: Non-adherence to inhaled medication poses a significant clinical and economic burden on patients with respiratory diseases. This narrative review provides an overview of key aspects of hair analysis, in general and specific for inhaled medications, and explores the potential of hair analysis as a novel tool to monitor adherence to inhaled medications.

Methods: PubMed searches were conducted to explore four aspects: (1) mechanisms of (inhaled) drug's systemic absorption and deposition in hair; (2) quantification of drugs in hair; (3) factors impacting (inhaled) drug hair concentrations; and (4) clinical studies assessing inhaled medication adherence through hair analysis.

Influence of ultrafiltration conditions on the unbound fraction of phenytoin and valproic acid.

Purpose: This study was designed to analyse the influence of temperature, pH and storage time on unbound fractions of PHT and VPA.

Methods: The influence of ultrafiltration (UF) temperature on measured unbound fractions of PHT and VPA in spiked samples was evaluated in a single laboratory experiment and in data from a national external quality control (EQC) database. The influence of pH adjustment with phosphate buffered saline (PBS) on measured unbound fractions of PHT and VPA was investigated in patient samples.

Validation of angiography-based FFR in non-culprit vessels of patients presenting with STEMI.

Background: Fractional flow reserve (FFR) for non-culprit lesions (NCLs) in patients with ST-elevation myocardial infarction (STEMI) can be influenced by temporary changes in microvascular resistance. Angiography-derived vessel fractional flow reserve (vFFR) has been tested as a less-invasive alternative.

Aims: The FAST STEMI II study aimed to assess the diagnostic performance of acute-setting vFFR vs.

Time below range alone is insufficient to identify severe hypoglycaemia risk in type 1 diabetes-the critical role of hypoglycaemia awareness: results from the SFDT1 study.

Aims/hypothesis: Severe hypoglycaemia events (SHE) remain frequent in people with type 1 diabetes despite advanced diabetes technologies. We examined whether time below range (TBR) 3.9 mmol/l (70 mg/dl; TBR70) or 3.

Identifying rehabilitation needs as part of secondary prevention in individuals with Atrial Fibrillation - a Delphi consensus study.

Aim: This study aimed to establish general consensus on a systematic needs assessment model to determine eligibility for cardiac rehabilitation (CR) as part of secondary prevention in individuals with atrial fibrillation (AF). Specific objectives included identifying relevant needs assessment criteria and establishing consensus on referral criteria.

Methods: A Delphi study was conducted following the ACCORD guidelines (ACcurate COnsensus Reporting Document) with participation of an international, multi-disciplinary expert panel including physicians, nurses and other healthcare professionals, across primary and secondary care as well as academic research.

Lacrimal gland ultrasonography shows superior reliability of OMERACT colour Doppler scoring compared to B-mode, in patients with clinically suspected Sjögren's disease.

Objective: To investigate the reliability of lacrimal gland ultrasound (LGUS) in patients with clinically suspected Sjögren's disease (SjD).

Method: Of 41 consecutive patients with clinically suspected SjD, 28 were diagnosed with SjD and 13 were classified as non-SjD. Forty patients were scored for bilateral lacrimal gland (LG) B-mode evaluation; LGs were 'not visible' in one case.

Novel prosthetic medial meniscus restores contact pressures to native values in a meniscectomized canine stifle.

Objective: The aim of this study was to ascertain whether a prosthetic meniscus adapts pressures to native tibial contact pressures in a canine stifle joint after total medial meniscectomy.

Study Design: Ex vivo biomechanical experimental study.

Sample Population: Seven cadaveric hindlimbs of seven large-breed dogs.

Clinical Impact of Continuation Versus Cessation of Antiviral Therapy in Chronic Hepatitis B: A Modelling Study With Implications for Hepatitis B Cure.

Discontinuing antivirals in chronic hepatitis B virus (HBV) 'e' antigen negative infection can enhance HBV surface antigen (HBsAg) loss but risks complications. We modelled the clinical impact of discontinuing antivirals in chronic HBV. We developed a Markov state model with Monte Carlo simulation of chronic HBV to compare continuation of antiviral therapy with 3 strategies of cessation and reinitiation for: (1) virologic relapse, (2) clinical relapse, or (3) hepatitis flare.

Lactococcal mobile genetic elements harbour a diverse phage defensome rich in restriction-modification systems.

The genomes of 43 distinct lactococcal strains were reconstructed by a combination of long- and short-read sequencing, resolving the plasmid complement and methylome of these strains. The genomes comprised 43 chromosomes of approximately 2.5 Mb each and 269 plasmids ranging from 2 to 211 kb (at an average occurrence of 6 per strain).

Eye tracking for the classification of visual function in individuals with vision impairment: A validation in Para athletes.

Eye tracking has the potential to be used as a meaningful measure of the consequences of vision impairment (VI), yet a comprehensive test battery is lacking. In this study, we sought to evaluate the feasibility and validity of a test battery of eye movements as a tool to measure visual performance in individuals with VI. A test battery including fixation stability, smooth pursuit, saccades, free viewing, and visual search was administered to 46 athletes with VI and 10 control participants.

First evaluation of a novel pulsatile LVAD: Feasibility and haemodynamic impact in acute heart failure.

Aims: Non-pharmacological therapies for acute decompensated heart failure (HF) and cardiogenic shock have evolved considerably in recent decades. Short-term mechanical circulatory support (MCS) devices can be used as circulatory backup. While nearly all available devices use continuous flow, evidence indicates that pulsatile flow can be more effective.

The Prevalence of Scapholunate Signal Abnormalities on Magnetic Resonance Imaging.

Background: Although trauma is a major cause of symptomatic scapholunate interosseous ligament (SLIL) pathology, many patients do not recall a specific injury or repetitive trauma. We report on: (1) the prevalence of SLIL signal changes in patients who underwent wrist magnetic resonance imaging (MRI) for various indications; and (2) the prevalence of SLIL signal changes on MRI in patients without prior wrist trauma.

Methods: This is a retrospective study evaluating 1021 patients who underwent wrist MRI or magnetic resonance arthrogram.