Altered cytoskeleton dynamics in patient-derived iPSC-based model of PCDH19 clustering epilepsy.

Protocadherin 19 (PCDH19) is an adhesion molecule involved in cell-cell interaction whose mutations cause a drug-resistant form of epilepsy, named PCDH19-Clustering Epilepsy (PCDH19-CE, MIM 300088). The mechanism by which altered PCDH19 function drive pathogenesis is not yet fully understood. Our previous work showed that PCDH19 dysfunction is associated with altered orientation of the mitotic spindle and accelerated neurogenesis, suggesting a contribution of altered cytoskeleton organization in PCDH19-CE pathogenesis in the control of cell division and differentiation.

Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

Montreal cognitive assessment as a cognitive outcome measure in progressive supranuclear palsy.

Background: The Montreal Cognitive assessment (MoCA) is a well-validated global cognitive screening instrument. Its validity in progressive supranuclear palsy (PSP) has not been assessed.

Objectives: To evaluate the MoCA as an outcome measure in PSP clinical trials.

Psychotropic medication usage in sporadic versus genetic behavioral-variant frontotemporal dementia.

Introduction: Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD.

Methods: We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study.

Profiles of the maternal occupational exposome during pregnancy and associations with intrauterine growth: Analysis of the French Longitudinal Study of Children - ELFE study.

Background: Numerous agents in the workplace are suspected of impairing fetal growth. To date, no epidemiological studies have specifically described the occupational exposome during pregnancy.

Objective: The objectives were to determine maternal occupational exposome profiles and study their associations with intrauterine growth characteristics measured by small for gestational age (SGA), birthweight (BW), and head circumference (HC).

Molecular and clinical Insights into KMT2E-Related O'Donnell-Luria-Rodan syndrome in a novel patient cohort.

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant neurodevelopmental disorder mainly characterized by global development delay/intellectual disability, white matter abnormalities, and behavioral manifestations. It is caused by pathogenic variants in the KMT2E gene. Here we report seven new patients with loss-of-function KMT2E variants, six harboring frameshift/nonsense changes, and one with a 7q22.

Impact of gender on the willingness to participate in clinical trials and undergo related procedures in individuals from an Alzheimer's prevention research cohort.

Background: Although there is growing evidence of the association between gender and early diagnosis of preclinical Alzheimer's disease, little attention has been given to the enrolment ratio of men and women in clinical trials and data reporting.

Methods: This study aims to analyze gender differences in sociodemographic factors associated with the willingness to participate in clinical trials and undergo specific procedures in the context of an Alzheimer's disease prevention research cohort. 2544 cognitively unimpaired participants from the ALFA parent cohort (age 45-75 years) of the Barcelonaβeta Brain Research Center were contacted through a structured phone call to determine their willingness to participate in Alzheimer's disease clinical trials and undergo trial-related procedures (magnetic resonance imaging, lumbar puncture, positron emission tomography, and cognitive assessment).

Prevalence and risk factors of maternal dissatisfaction after vaginal delivery: A multicenter prospective study.

Objective: To evaluate the prevalence and risk factors of maternal dissatisfaction 2 days after a singleton vaginal delivery at or near term.

Methods: We conducted a planned ancillary cohort study of the TRanexamic Acid for Preventing Postpartum Hemorrhage After Vaginal Delivery (TRAAP) randomized controlled trial. Maternal dissatisfaction, related to the birth and to the subsequent hospital stay, was assessed 2 days postpartum by two self-administered questions: "Are you satisfied with the care you received during your child's birth?" and "Are you satisfied with the care you have received during your hospital stay?".

Analysis of Concussions with Persisting Symptoms Caused by Motor Vehicle Crashes in 136 Vehicle Occupants Shows that Females Are Vulnerable Road Users.

At the Canadian Concussion Centre, we treated 136 patients from 2000 to 2020 who sustained concussion plus persisting concussion symptoms (C+PCS) as motor vehicle occupants involved in motor vehicle crashes (MVCs). This center specializes in the treatment of patients with C+PCS. The objective of the present study was to identify strategies for preventing concussion among vehicle occupants involved in MVC.

Skipping of Exon 20 in EP300: A Novel Variant Linked to Rubinstein-Taybi Syndrome With Atypical and Severe Clinical Manifestations.

Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder linked to haploinsufficiency of CREBBP (RSTS1) and EP300 (RSTS2) genes. Characteristic features often include distinctive facial traits, broad thumbs and toes, short stature, and various degrees of intellectual disability. The clinical presentation of RSTS is notably variable, making it challenging to establish a clear genotype-phenotype correlation, except for specific variants which cause the allelic Menke-Hennekam syndrome.

Autoinflammatory patients with Golgi-trapped CDC42 exhibit intracellular trafficking defects leading to STING hyperactivation and ER stress.

Most autoinflammatory diseases are caused by mutations in innate immunity genes. Previously, four variants in the RHO GTPase CDC42 were discovered in patients affected by syndromes generally characterized by neonatal-onset of cytopenia and auto-inflammation, including hemophagocytic lymphohistiocytosis and rash in the most severe form (NOCARH syndrome). However, the mechanisms responsible for these phenotypes remain largely elusive.

Association of Initial Side of Brain Atrophy With Clinical Features and Disease Progression in Patients With Frontotemporal Dementia.

Background And Objectives: Pathogenic variants in the gene cause frontotemporal dementia (FTD-) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD- depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease.

Improvement of fatigue, depression, and processing speed two weeks post Natalizumab infusion in Multiple Sclerosis: No difference between standard and extended interval dosing schedules.

Background: Fatigue, depression and slow processing speed are debilitating symptoms in people with Relapsing-Remitting Multiple Sclerosis (RRMS) that significantly impacts on the quality of life. Natalizumab, a disease-modifying treatment, improves clinical symptoms but questions remain about the comparative efficacy between its standard interval dosing (SID) and extended interval dosing (EID) schedules.

Objective: To examine the impact of short term natalizumab dosing schedules-SID versus EID-on the so called "invisible symptoms", specifically focusing on symptom exacerbation during the 'wearing-off' phase before infusion and the subsequent relief post-infusion.

Best practices for germline variant and DNA methylation analysis of second- and third-generation sequencing data.

This comprehensive review provides insights and suggested strategies for the analysis of germline variants using second- and third-generation sequencing technologies (SGS and TGS). It addresses the critical stages of data processing, starting from alignment and preprocessing to quality control, variant calling, and the removal of artifacts. The document emphasized the importance of meticulous data handling, highlighting advanced methodologies for annotating variants and identifying structural variations and methylated DNA sites.

Brain malformations and seizures by impaired chaperonin function of TRiC.

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures.

Informant characteristics influence Clinical Dementia Rating Sum of Boxes scores-based staging of Alzheimer's disease.

The Clinical Dementia Rating Sum of Boxes (CDR-SB) is a staging scale for Alzheimer's disease (AD) and is commonly used as an outcome in clinical trials. It relies on information provided by the patient and an informant. The CDR-SB should reflect only the patient's disease severity.

Frontoparietal network integrity supports cognitive function in pre-symptomatic frontotemporal dementia: Multimodal analysis of brain function, structure, and perfusion.

Introduction: Genetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion, and functional patterns in the pre-symptomatic stage could inform accurate staging and potential mechanisms.

Methods: We included 207 pre-symptomatic genetic mutation carriers and 188 relatives without mutations.

Changes in the proteomics and metabolomics profiles of Cormus Domestica (L.) fruits during the ripening process.

Background: Cormus domestica (L.) is a monophyletic wild fruit tree belonging to the Rosaceae family, with well-documented use in the Mediterranean region. Traditionally, these fruits are harvested and stored for at least 2 weeks before consumption.

Fluorescent Labeling Can Significantly Perturb Measured Binding Affinity and Selectivity of Peptide-Protein Interactions.

Peptide-based drugs are powerful inhibitors of therapeutically relevant protein-protein interactions. Their affinity and selectivity for target proteins are commonly assessed using fluorescence-based assays such as anisotropy/polarization or quantitative microarrays. This study reveals that labeling can perturb peptide/protein binding by more than 1 order of magnitude.