Cenobamate as add-on treatment for SCN8A developmental and epileptic encephalopathy.

Objectives: Developmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. High doses of sodium channel blockers are typically used to treat SCN8A-DEE caused by gain-of-function (GoF) variants. However, seizures are often drug resistant, and only a few patients achieve seizure freedom.

[Preparing for patient work founded on evidence in medical school - a questionnaire study on final-year medical students].

Several of the requirements for obtaining a medical degree according to the Swedish Higher Education Ordinance illustrate the scientific basis of the profession, and systematic reviews as well as health technology assessments (HTA) constitute cornerstones in evidence-based medicine. In this study, medical students' experience of scientific education related to the profession was explored, and their knowledge achieved was sampled by five multiple-choice questions (MCQ). A total of 433 out of 641 students attending the final semester in six medical schools in Sweden participated (response rate: 68%).

Earth's most needed uncultivated aquatic prokaryotes.

Aquatic ecosystems house a significant fraction of Earth's biosphere, yet most prokaryotes inhabiting these environments remain uncultivated. While recently developed genome-resolved metagenomics and single-cell genomics techniques have underscored the immense genetic breadth and metabolic potential residing in uncultivated Bacteria and Archaea, cultivation of these microorganisms is required to study their physiology via genetic systems, confirm predicted biochemical pathways, exploit biotechnological potential, and accurately appraise nutrient turnover. Over the past two decades, the limitations of culture-independent investigations highlighted the importance of cultivation in bridging this vast knowledge gap.

Understanding paralogous epilepsy-associated GABA receptor variants: Clinical implications, mechanisms, and potential pitfalls.

Recent discoveries have revealed that genetic variants in γ-aminobutyric acid type A (GABA) receptor subunits can lead to both gain-of-function (GOF) and loss-of-function (LOF) receptors. GABA receptors, however, have a pseudosymmetrical pentameric assembly, and curiously diverse functional outcomes have been reported for certain homologous variants in paralogous genes (paralogous variants). To investigate this, we assembled a cohort of 11 individuals harboring paralogous M1 proline missense variants in , , and Seven mutations (α1, α1, β2, β3, β3, γ2, and γ2) in α1β2/3γ2 receptors were analyzed using electrophysiological examinations and molecular dynamics simulations.

Quantitative EEG biomarkers for STXBP1-related disorders.

Objective: EEG patterns and quantitative EEG (qEEG) features have been poorly explored in monogenic epilepsies. Herein, we investigate regional differences in EEG frequency composition in patients with STXBP1 developmental and epileptic encephalopathy (STXBP1-DEE).

Methods: We conducted a retrospective study collecting electroclinical data of patients with STXBP1-DEE and two control groups of patients with DEEs of different etiologies and typically developing individuals matched for age and sex.