Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).

Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.

Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.

Reduced antioxidant high-density lipoprotein function in heart failure with preserved ejection fraction.

Background: Heart failure (HF) is a heterogeneous clinical syndrome affecting a growing global population. Due to the high incidence of cardiovascular risk factors, a large proportion of the Western population is at risk for heart failure. Oxidative stress and inflammation play a crucial role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF).

Content Validity 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 validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA.

The Relationship between Noise Pollution and Depression and Implications for Healthy Aging: A Spatial Analysis Using Routinely Collected Primary Care Data.

Environmental noise is a significant public health concern, ranking among the top environmental risks to citizens' health and quality of life. Despite extensive research on atmospheric pollution's impact on mental health, spatial studies on noise pollution effects are lacking. This study fills this gap by exploring the association between noise pollution and depression in England, with a focus on localised patterns based on area deprivation.

Trypanosomosis and Transhumance: Contributions to Contemporary Conflicts Between Farmers and Herdsmen Along the Tsetse Fly Belts: Mathematical Modeling and Systematic Field Analysis Approach.

Conflicts within the tsetse fly belt revealed a strong correlation between the dynamics of bovine trypanosomosis and the insurgency involving farmers and herders in Nigeria and parts of West Africa. This study examined the history, causes and influence of farmers-herdsmen conflicts on banditry, terrorism and food security as it relates to the epidemiology of African animal trypanosomosis (AAT). A combination of literature database searches, semi-structured questionnaires, and mathematical modeling was employed.

Soma and neurite density abnormalities of paramagnetic rim lesions and core-sign lesions in multiple sclerosis.

Background: In multiple sclerosis (MS), susceptibility-weighted imaging (SWI) may reveal white matter lesions (WML) with a paramagnetic rim ("paramagnetic rim lesions" [PRLs]) or diffuse hypointensity ("core-sign lesions"), reflecting different stages of WML evolution.

Objective: Using the soma and neurite density imaging (SANDI) model on diffusion-weighted magnetic resonance imaging (MRI), we characterized microstructural abnormalities of MS PRLs and core-sign lesions and their clinical relevance.

Methods: Forty MS patients and 20 healthy controls (HC) underwent a 3 T brain MRI.

Predictors of drooling severity in people with Parkinson's disease.

Background: Drooling, defined as the unintentional loss of saliva from the anterior oral cavity, remains poorly understood in terms of the underlying clinical factors in people with Parkinson's disease (PwP). This study aims to clarify these factors by analyzing predictors and secondarily the correlates with the severity of drooling in PwP.

Methods: We conducted a cross-sectional study involving 42 PwP with drooling and 59 without drooling.

[Chronic back pain-pharmacological and nonpharmacological treatment approaches].

Chronic back pain is a global health problem with significant impacts on physical and mental health, work ability, and quality of life. Back pain has an increased risk of becoming chronic, especially in patients with other chronic conditions. Treatment primarily focuses on nonpharmacological approaches.

Investigating the Constraints and Mitigation Strategies for the Adoption of Sustainable Land Management Practices in Erosion-prone Areas of Southeast Nigeria.

The adoption of sustainable land management practices (SLMPs) is crucial to improve soil health, and farm yield, and potentially limit the degradation of agricultural and ecological systems. However, farmers still encounter diverse challenges when trying to implement SLMPs. Research on the potential mitigation strategies to address the complex challenges to the adoption of SLMPs in the developing countries context is limited.

An audit on the assessment and management of osteoporosis in a Parkinson's and related diseases clinic in Australia.

Background: Patients with Parkinson's disease (PD) and atypical parkinsonian syndromes are at increased risk of falls and should be actively screened and treated for osteoporosis. In 2024, the Royal Australian College of General Practitioners (RACGP) revised their practice guidelines for diagnosing and managing osteoporosis in postmenopausal women and men aged over 50 years.

Objective: We conducted the first Australian study to audit these guidelines in patients with PD and atypical parkinsonian syndromes.

Cerebral vasculitis related to neurosarcoidosis: a case series and systematic literature review.

Cerebral vasculitis is a rare but severe manifestation of neurosarcoidosis (NS) that has received little attention. The aim of the present study was to characterize clinical and diagnostic features as well as potential treatment strategies of cerebral vasculitis related to NS. We assessed 29 patients with cerebral vasculitis related to NS (15 female, mean age at time of diagnosis 45 years, SD = 11.

Development of a novel laboratory approach for evaluating the adhesion strength of biofilms to human dentine.

Introduction: Biofilms may show varying adherence strengths to dentine. This study quantified the shear force required for the detachment of multispecies biofilm from the dentine using fluid dynamic gauging (FDG) and computation fluid dynamics (CFD). To date this force has not been quantified.

Mesoscale modelling of fibrin clots: the interplay between rheology and microstructure at the gel point.

This study presents a numerical model for incipient fibrin-clot formation that captures characteristic rheological and microstructural features of the clot at the gel point. Using a mesoscale-clustering framework, we evaluate the effect of gel concentration or gel volume fraction and branching on the fractal dimension, the gel time, and the viscoelastic properties of the clots. We show that variations in the gel concentration of our model can reproduce the effect of thrombin in the formation of fibrin clots.

Neutral and ionic Co(II) metal-organic frameworks with 2-methylimidazole and trimesate: design and evaluation for molecule encapsulation and slow release.

Two Co(II) mixed-ligand metal-organic frameworks (MOFs) based on 2-methylimidazole and trimesate were synthesised at room temperature. The structure and properties of the two MOFs, named material Deutsches Elektronen Synchrotron-1 and -2 (mDESY-1 and mDESY-2), were verified by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), SQUID magnetic susceptibility and N adsorption. The structural analysis indicates that mDESY-1 is a 3D ionic framework with 2-methyl-1-imidazol-3-ium counterions residing in its pores, while mDESY-2 is a 2D neutral framework isostructural to ITH-1, with water as a co-crystallising solvent.

Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.

Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.

Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.

NR1D1 Inhibition Enhances Autophagy and Mitophagy in Alzheimer's Disease Models.

Alzheimer's disease (AD) is marked by extracellular beta-amyloid (Aβ) plaques and intracellular Tau tangles, leading to progressive cognitive decline and neuronal dysfunction. Impaired autophagy, a process by which a cell breaks down and destroys damaged or abnormal proteins and other substances, contributes to AD progression. This study investigated Nuclear Receptor Subfamily 1 Group D Member 1 (NR1D1) as a potential therapeutic target for modulating autophagy.

Multivariable MR Can Mitigate Bias in Two-Sample MR Using Covariable-Adjusted Summary Associations.

Genome-wide association studies (GWAS) are hypothesis-free studies that estimate the association between polymorphisms across the genome with a trait of interest. To increase power and to estimate the direct effects of these single-nucleotide polymorphisms (SNPs) on a trait GWAS are often conditioned on a covariate (such as body mass index or smoking status). This adjustment can introduce bias in the estimated effect of the SNP on the trait.

Transferability of Single- and Cross-Tissue Transcriptome Imputation Models Across Ancestry Groups.

Transcriptome-wide association studies (TWAS) investigate the links between genetically regulated gene expression and complex traits. TWAS involves imputing gene expression using expression quantitative trait loci (eQTL) as predictors and testing the association between the imputed expression and the trait. The effectiveness of TWAS depends on the accuracy of these imputation models, which require genotype and gene expression data from the same samples.

Lower Risk of New-Onset Atrial Fibrillation in Conduction System Pacing Compared With Right Ventricular Pacing.

Background: Conduction system pacing (CSP) has been reported to improve clinical outcomes in comparison of right ventricular pacing (RVP). However, the performance between CSP and RVP on the risk of new-onset atrial fibrillation (AF) remains elusive.

Methods: Four online databases were systematically searched up to July 1, 2024.

Clinical Trial: Study to Investigate the Efficacy and Safety of the Alpha-2-Delta Ligand PD-217,014 in Patients With Irritable Bowel Syndrome.

Introduction: Despite the emergence of drugs to treat irritable bowel syndrome (IBS), improving abdominal pain can still be challenging. αδ ligands, such as gabapentin and pregabalin, are sometimes used off-label to tackle this problem. However, evidence for efficacy is limited, and no large-scale studies have been published.

Factor VIII Antibodies Demonstrate Type I or Type II Kinetics in Acquired Haemophilia A.

Background: Acquired haemophilia A (AHA) is an acquired bleeding disorder resulting from autoantibodies against Factor VIII (FVIII). Previous studies have reported differences in FVIII inhibitor kinetics (type I or type II) in AHA compared to severe haemophilia A.

Aim: To characterise inhibitor kinetics in AHA and evaluate the proportions displaying type I, II or indeterminate kinetics.

Challenges in determining the global burden of non-malignant central nervous system tumors: an analysis of international incidence and mortality data sources.

Background: Non-malignant tumors of the CNS contribute substantially to the morbidity and mortality from CNS tumors. It is critical to understand the epidemiology of non-malignant CNS tumors separately from CNS malignancies to inform resource allocation and policy since treatment and prognosis can differ. High quality international data on non-malignant CNS tumor burden are needed to accomplish this goal.