δ-containing GABA receptors on parvalbumin interneurons modulate neuronal excitability and network dynamics in the mouse medial prefrontal cortex.

In medial prefrontal cortex (mPFC), fast-spiking parvalbumin (PV) interneurons regulate excitability and microcircuit oscillatory activity important for cognition. Although PV interneurons inhibit pyramidal neurons, they themselves express δ subunits of GABA receptors important for slow inhibition. However, the specific contribution of δ-containing GABA receptors to the function of PV interneurons in mPFC is unclear.

Nitrous Oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect.

Nitrous oxide (NO) induces rapid and durable antidepressant effects. The cellular and circuit mechanisms mediating this process are not known. Here we find that a single dose of inhaled NO induces rapid and specific activation of layer V (L5) pyramidal neurons in the cingulate cortex of rodents exposed to chronic stress conditions.

Optical genome mapping: Unraveling complex variations and enabling precise diagnosis in dystrophinopathy.

Objective: Approximately 7% of individuals with dystrophinopathy remain undiagnosed at the genetic level using conventional genetic tests like multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS). We used the optical genome mapping (OGM) technology to detect and analyze uncommon mutations or structural variations (SVs) within the DMD gene, thus contributing to more precise clinical diagnoses.

Methods: We herein included eight patients with dystrophinopathy (six males and two females) in whom pathogenic variants of the DMD gene could not be accurately identified using MLPA and NGS.

Attention Transfer in Heterogeneous Networks Fusion for Drug Repositioning.

Computational drug repositioning which accelerates the process of drug development is able to reduce the cost in terms of time and money dramatically which brings promising and broad perspectives for the treatment of complex diseases. Heterogeneous networks fusion has been proposed to improve the performance of drug repositioning. Due to the difference and the specificity including the network structure and the biological function among different biological networks, it poses serious challenge on how to represent drug features and construct drug-disease associations in drug repositioning.

Association of LONP1 gene with epilepsy and the sub-regional effect.

The LONP1 gene encodes Lon protease, which is responsible for degrading damaged or misfolded proteins and binding mitochondrial DNA. Previously, LONP1 variants have been identified in patients with cerebral, ocular, dental, auricular, and skeletal anomalies (CODAS syndrome) and mitochondrial diseases. Seizures were occasionally observed.

Modeling late-onset Alzheimer's disease neuropathology via direct neuronal reprogramming.

Late-onset Alzheimer's disease (LOAD) is the most common form of Alzheimer's disease (AD). However, modeling sporadic LOAD that endogenously captures hallmark neuronal pathologies such as amyloid-β (Aβ) deposition, tau tangles, and neuronal loss remains an unmet need. We demonstrate that neurons generated by microRNA (miRNA)-based direct reprogramming of fibroblasts from individuals affected by autosomal dominant AD (ADAD) and LOAD in a three-dimensional environment effectively recapitulate key neuropathological features of AD.

Nusinersen effectiveness and safety in pediatric patients with 5q-spinal muscular atrophy: a multi-center disease registry in China.

Objective: To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients.

Methods: Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively.

δ-containing GABA receptors on parvalbumin interneurons modulate neuronal excitability and network dynamics in the mouse medial prefrontal cortex.

Unlabelled: In medial prefrontal cortex (mPFC), fast-spiking parvalbumin (PV) interneurons regulate excitability and microcircuit oscillatory activity important for cognition. Although PV interneurons inhibit pyramidal neurons, they themselves express δ subunits of GABAA receptors important for slow inhibition. However, the specific contribution of δ-containing GABAA receptors to the function of PV interneurons in mPFC is unclear.

A Post-Marketing Surveillance Study of Nusinersen for Spinal Muscular Atrophy in Routine Medical Practice in China: Interim Results.

Introduction: Spinal muscular atrophy (SMA) is a rare, autosomal recessive, neuromuscular disease that leads to progressive muscular weakness and atrophy. Nusinersen, an antisense oligonucleotide, was approved for SMA in China in February 2019. We report interim results from a post-marketing surveillance phase 4 study, PANDA (NCT04419233), that collects data on the safety, efficacy, and pharmacokinetics of nusinersen in children with SMA in routine clinical practice in China.

A role for δ subunit-containing GABA receptors on parvalbumin positive neurons in maintaining electrocortical signatures of sleep states.

Unlabelled: GABA receptors containing δ subunits have been shown to mediate tonic/slow inhibition in the CNS. These receptors are typically found extrasynaptically and are activated by relatively low levels of ambient GABA in the extracellular space. In the mouse neocortex, δ subunits are expressed on the surface of some pyramidal cells as well as on parvalbumin positive (PV+) interneurons.

Efficacy and safety of perampanel as the first add-on therapy for children with epilepsy: A real-world multicenter prospective observational study.

Objective: Perampanel (PER) is a new anti-seizure medication (ASM) with a novel mechanism of action. This study aimed to determine the efficacy and safety of PER when added to monotherapy in children and adolescents (age, 4-18 years) with epilepsy.

Method: A multicenter prospective observational study was performed on children and adolescents (age, 4-18 years) with epilepsy who did not respond to ASM monotherapy between July 2021 and October 2022.

TARSL: Triple-Attention Cross-Network Representation Learning to Predict Synthetic Lethality for Anti-Cancer Drug Discovery.

Cancer is a multifaceted disease that results from co-mutations of multi biological molecules. A promising strategy for cancer therapy involves in exploiting the phenomenon of Synthetic Lethality (SL) by targeting the SL partner of cancer gene. Since traditional methods for SL prediction suffer from high-cost, time-consuming and off-targets effects, computational approaches have been efficient complementary to these methods.

Endogenous recapitulation of Alzheimer's disease neuropathology through human 3D direct neuronal reprogramming.

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily affects elderly individuals, and is characterized by hallmark neuronal pathologies including extracellular amyloid-β (Aβ) plaque deposition, intracellular tau tangles, and neuronal death. However, recapitulating these age-associated neuronal pathologies in patient-derived neurons has remained a significant challenge, especially for late-onset AD (LOAD), the most common form of the disorder. Here, we applied the high efficiency microRNA-mediated direct neuronal reprogramming of fibroblasts from AD patients to generate cortical neurons in three-dimensional (3D) Matrigel and self-assembled neuronal spheroids.

Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

Purpose: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy.

Methods: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy.

Allopregnanolone Effects on Inhibition in Hippocampal Parvalbumin Interneurons.

Allopregnanolone (AlloP) is a neurosteroid that potentiates ionotropic GABAergic (GABA) inhibition and is approved for treating postpartum depression in women. Although the antidepressant mechanism of AlloP is largely unknown, it could involve selective action at GABA receptors containing the δ subunit. Despite previous evidence for selective effects of AlloP on α4/δ-containing receptors of hippocampal dentate granule cells (DGCs), other recent results failed to demonstrate selectivity at these receptors (Lu et al.

Long-term outcomes of infantile spasms in children treated with ketogenic diet therapy in combination with anti-seizure medications in a resource-limited region.

Objective: Despite numerous guidelines, the overall outcome of infantile spasms is poor, with only a small number of patients being able to attend school. The purpose of this study was to investigate long-term outcomes. Patients had poor access to the recommended first-line anti-seizure medications (ASMs), such as hormones (corticotropin or prednisolone/prednisone) and vigabatrin, and their alternative treatment was other ASMs and a ketogenic diet.

MAGCN: A Multiple Attention Graph Convolution Networks for Predicting Synthetic Lethality.

Synthetic lethality (SL) is a potential cancer therapeutic strategy and drug discovery. Computational approaches to identify synthetic lethality genes have become an effective complement to wet experiments which are time consuming and costly. Graph convolutional networks (GCN) has been utilized to such prediction task as be good at capturing the neighborhood dependency in a graph.

Rasch analysis of the 32-item motor function measure in ambulant patients with Duchenne muscular dystrophy.

Objective: This study analyzed the 32-item Motor Function Measure in a cohort of ambulatory patients with Duchenne muscular dystrophy using Rasch measurement methods.

Design: This is a psychometric study.

Setting: Rehabilitation centre of a large public children's hospital in Shenzhen, China.

Chronic pain, psychological distress, and quality of life in males with Duchenne muscular dystrophy.

Aim: To describe chronic pain in Duchenne muscular dystrophy (DMD) from children's/adolescents' perspectives, explore patient variables associated with self-reported pain, and examine the relationship between chronic pain, psychological functioning, and health-related quality of life (HRQoL).

Method: This observational study included a paediatric cohort (aged 8-18 years; median age 9 years 4 months) with DMD under multidisciplinary care (n = 45). Clinical data of the latest visit were extracted from the electronic health record and assessment of pain, psychological distress, and HRQoL were performed during the same visit.

Recessive Mutations Are Associated With Febrile Seizures and Epilepsy With Antecedent Febrile Seizures and the Genotype-Phenotype Correlation.

Objective: The encodes polycystin-1, a large transmembrane protein that plays important roles in cell proliferation, apoptosis, and cation transport. Previous studies have identified mutations in autosomal dominant polycystic kidney disease (ADPKD). However, the expression of in the brain is much higher than that in the kidney.

Is Associated With X-Linked Partial (Focal) Epilepsy With Antecedent Febrile Seizures.

Objective: mutations were associated with X-linked intellectual developmental disorder-109 and in males with autism spectrum disorder (ASD). The relationship between and epilepsy has not been defined.

Method: Trios-based whole-exome sequencing was performed in a cohort of 372 unrelated cases (families) with partial (focal) epilepsy without acquired causes.