Targeting heterozygous dominant negative variant of using Gapmer ASO for the treatment of drug-resistant epilepsy.

A missense mutation c.1220C>G of gene was recently identified in an infant with epilepsy. encodes K1.

Secreted dengue virus NS1 from infection is predominantly dimeric and in complex with high-density lipoprotein.

Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab.

Molecular and Phenotypic Characterization of the -Related Disorder.

Background And Objectives: Heterozygous variants in RAR-related orphan receptor B () have recently been associated with susceptibility to idiopathic generalized epilepsy. However, few reports have been published so far describing pathogenic variants of this gene in patients with epilepsy and intellectual disability (ID). In this study, we aimed to delineate the epilepsy phenotype associated with pathogenic variants and to provide arguments in favor of the pathogenicity of variants.

Single-cell transcriptomics and surface epitope detection in human brain epileptic lesions identifies pro-inflammatory signaling.

Epileptogenic triggers are multifactorial and not well understood. Here we aimed to address the hypothesis that inappropriate pro-inflammatory mechanisms contribute to the pathogenesis of refractory epilepsy (non-responsiveness to antiepileptic drugs) in human patients. We used single-cell cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to reveal the immunotranscriptome of surgically resected epileptic lesion tissues.

Unique Severe HyperEkplexia-Like Apneic Events (SHELAE) Improved by High-Dose Piracetam.

Breath-holding spells are common non-epileptic events with onset between 6 months and 18 months of age that are usually triggered by minor painful events or strong emotions. Symptomatic treatments for breath-holding spells include iron supplementation, glycopyrrolate and piracetam. Hyperekplexia is a rare non-epileptic disorder characterized by generalized hypertonia and exaggerated startle.

Pro-inflammatory, IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy.

Drug refractory epilepsy (RE) is a chronic neurological disease with varied etiology that represents a group of patients whose seizures do not respond to anti-epileptic drugs. The immune system may have a role in seizure and epilepsy development, but the specific mechanisms of inflammation that lead to epileptogenesis and contribute to RE are unknown. Here, we used mass cytometry to comprehensively study the immune system of pediatric patients with RE and compared their immune profile and function with patients with age-matched autoimmune encephalitis (AIE) and healthy controls.

Filaria specific antibody response profiling in plasma from anti-retroviral naïve Loa loa microfilaraemic HIV-1 infected people.

Background: In West and Central Africa areas of endemic Loa loa infections overlap with regions of high prevalence of human immunodeficiency virus type 1 (HIV-1) infections. Because individuals in this region are exposed to filarial parasites from birth, most HIV-1 infected individuals invariably also have a history of filarial parasite infection. Since HIV-1 infection both depletes immune system and maintains it in perpetual inflammation, this can hamper Loa loa filarial parasite mediated immune modulation, leading to enhanced loaisis.

Dendritic cell targeted HIV-1 gag protein vaccine provides help to a recombinant Newcastle disease virus vectored vaccine including mobilization of protective CD8 T cells.

Introduction: Recombinant Newcastle Disease virus (rNDV) vectored vaccines are safe mucosal applicable vaccines with intrinsic immune-modulatory properties for the induction of efficient immunity. Like all viral vectored vaccines repeated inoculation via mucosal routes invariably results to immunity against viral vaccine vectors. To obviate immunity against viral vaccine vectors and improve the ability of rNDV vectored vaccines in inducing T cell immunity in murine air way we have directed dendritic cell targeted HIV-1 gag protein (DEC-Gag) vaccine; for the induction of helper CD4 T cells to a Recombinant Newcastle disease virus expressing codon optimized HIV-1 Gag P55 (rNDV-L-Gag) vaccine.

Clinical and molecular characterization of -related severe early-onset epilepsy.

Objective: To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset epilepsy.

Methods: We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified variants on local diagnostic multiple gene panel testing were also included.

Mutations in a Sibship with Multifocal Polymyoclonus.

Background: Advances in molecular genetic technologies have improved our understanding of genetic causes of rare neurological disorders with features of myoclonus.

Case Report: A family with two affected siblings, presenting with multifocal polymyoclonus and neurodevelopmental delay, was recruited for whole-exome sequencing following unyielding diagnostic neurometabolic investigations. Compound heterozygous mutations in , a gene previously associated with various epilepsy phenotypes and hearing loss, were identified in both siblings.

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings.

RARS2 mutations in a sibship with infantile spasms.

Pontocerebellar hypoplasia is a group of heterogeneous neurodevelopmental disorders characterized by reduced volume of the brainstem and cerebellum. We report two male siblings who presented with early infantile clonic seizures, and then developed infantile spasms associated with prominent isolated cerebellar hypoplasia/atrophy on magnetic resonance imaging (MRI). Using whole exome sequencing techniques, both were found to be compound heterozygotes for one previously reported and one novel mutation in the gene encoding mitochondrial arginyl-tRNA synthetase 2 (RARS2).

Delineation of the movement disorders associated with FOXG1 mutations.

Objective: The primary objective of this research was to characterize the movement disorders associated with FOXG1 mutations.

Methods: We identified patients with FOXG1 mutations who were referred to either a tertiary movement disorder clinic or tertiary epilepsy service and retrospectively reviewed medical records, clinical investigations, neuroimaging, and available video footage. We administered a telephone-based questionnaire regarding the functional impact of the movement disorders and perceived efficacy of treatment to the caregivers of one cohort of participants.

Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.

Background: We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay.

Methods: In 400 patients with these disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis.

Results: We identified causative mutations in 71/400 patients (18%).

GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy.

The gamma-aminobutyric acid type A receptor β3 gene (GABRB3) encodes the β3-subunit of the gamma-aminobutyric acid type A (GABAA ) receptor, which mediates inhibitory signalling within the central nervous system. Recently, GABRB3 mutations have been identified in a few patients with infantile spasms and Lennox-Gastaut syndrome. We report the clinical and electrographic features of a novel case of GABRB3-related early-onset epileptic encephalopathy.

Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum.

Homozygous deletions of chromosome 20p12.3, disrupting the promoter region and first three coding exons of the phospholipase C β1 gene (PLCB1), have previously been described in two reports of early infantile epileptic encephalopathy (EIEE). Both children were born to consanguineous parents, one presented with infantile spasms, the other with migrating partial seizures of infancy.

Mycobacterium tuberculosis is the causative agent of tuberculosis in the southern ecological zones of Cameroon, as shown by genetic analysis.

Background: Tuberculosis (TB) is a major cause of mortality and suffering worldwide, with over 95% of TB deaths occurring in low- and middle-income countries. In recent years, molecular typing methods have been widely used in epidemiological studies to aid the control of TB, but this usage has not been the case with many African countries, including Cameroon. The aims of the present investigation were to identify and evaluate the diversity of the Mycobacterium tuberculosis complex (MTBC) isolates circulating in two ecological zones of Cameroon, seven years after the last studies in the West Region, and after the re-organization of the National TB Control Program (NTBCP).

Effects of a written asthma action plan on caregivers' management of children with asthma: a cross-sectional questionnaire survey.

Background: Caregivers of children with asthma provided with a written asthma action plan (WAAP) are reported to be more confident in their ability to provide care for their child during an asthma exacerbation. However, little is known about how a WAAP impacts on their care processes that contributed to this increased confidence.

Aims: To determine the effects of a WAAP on caregivers' understanding of asthma symptoms, their use of asthma medications for their children, and acute care visits to consult their physicians.

[Visceral leishmaniasis, pemphigus and immunosuppressive treatment: case report from Morocco].

Atypical forms of visceral leishmaniasis associated with immunosuppressive treatment are difficult to diagnose and cause high mortality. The purpose of this report is to describe a case involving a 42-year-old patient living in a leishmaniasis-endemic area, who was undergoing immunosuppressive treatment using corticosteroids and methotrexate for pemphigus. Despite clinical and laboratory findings consistent with visceral leishmaniasis, detection of Leishmania bodies was a coincidental finding of cytological examination of bone marrow during workup for pancytopenia and associated clinical signs.

Factors influencing family physicians' drug prescribing behaviour in asthma management in primary care.

Introduction: Little is known about the decision pathway that family physicians (FP) take in considering drug therapy for their asthma patients. This study aimed to explore the factors that influence FPs' decisions in prescribing medications for their asthma patients.

Methods: A qualitative method using focus group discussions (FGD) was used to gather qualitative data based on a semi-structured topic guide from FPs of different training backgrounds and practices.

A qualitative study of factors influencing family physicians' prescription of the Written Asthma Action Plan in primary care in Singapore.

Introduction: The Written Asthma Action Plan (WAAP) educates patients on the early recognition and treatment of deteriorating asthma. It has been adopted in Singapore polyclinics and restructured hospitals in the past few years as recommended by the Singapore National Asthma Programme. Local asthma patients can choose to be treated by family physicians at public polyclinics or by private general practitioners (GPs).