Brodalumab Is Effective for Psoriasis Patients with Difficult-To-Treat Body Regions: Results from an Observational Clinical Study.

Introduction: Brodalumab, a human monoclonal antibody that selectively inhibits the interleukin (IL)-17 receptor subunit A, has been approved for the treatment of moderate-to-severe plaque psoriasis. The treatment benefit of brodalumab has been clearly demonstrated in multiple clinical studies. However, data on effectiveness for difficult-to-treat body regions, especially in everyday clinical practice, are still limited.

Impact of different classes of immune-modulating treatments on B cell-related and T cell-related immune response before and after COVID-19 booster vaccination in patients with immune-mediated diseases and primary immunodeficiency: a cohort study.

Objectives: To evaluate the potential of immunosuppressed patients to mount B-cell and T-cell responses to COVID-19 booster vaccination (third vaccination).

Methods: Patients with primary immunodeficiency (PID), immune-mediated inflammatory diseases (IMIDs) on CD20-depleting treatment with rituximab (RTX), or IMIDs treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biological disease-modifying antirheumatic drug (bDMARDs) were included and assessed before (baseline visit (BL)) and 2, 4 and 8 weeks after COVID-19 booster vaccination. Serum B-cell responses were assessed by antibody levels against SARS-CoV-2 spike protein (anti-spike IgG antibody (S-AB)) and a surrogate virus neutralisation test (sVNT).

Loss of the Immunomodulatory Transcription Factor BATF2 in Humans Is Associated with a Neurological Phenotype.

Epilepsy and mental retardation are known to be associated with pathogenic mutations in a broad range of genes that are expressed in the brain and have a role in neurodevelopment. Here, we report on a family with three affected individuals whose clinical symptoms closely resemble a neurodevelopmental disorder. Whole-exome sequencing identified a homozygous stop-gain mutation, p.

Large Phenotypic Variation of Individuals from a Family with a Novel Mutation Associated with Microcephaly, Epilepsy, and Behavioral and Cognitive Deficits.

Here, we report a consanguineous family harboring a novel homozygous frame-shift mutation in leading to a truncation of the ASPM protein after amino acid position 1830. The phenotype of the patients was associated with microcephaly, epilepsy, and behavioral and cognitive deficits. Despite the obvious genetic similarity, the affected patients show a considerable phenotypic heterogeneity regarding the degree of mental retardation, presence of epilepsy and MRI findings.

Cytosolic, but not matrix, calcium is essential for adjustment of mitochondrial pyruvate supply.

Mitochondrial oxidative phosphorylation (OXPHOS) and cellular workload are tightly balanced by the key cellular regulator, calcium (Ca). Current models assume that cytosolic Ca regulates workload and that mitochondrial Ca uptake precedes activation of matrix dehydrogenases, thereby matching OXPHOS substrate supply to ATP demand. Surprisingly, knockout (KO) of the mitochondrial Ca uniporter (MCU) in mice results in only minimal phenotypic changes and does not alter OXPHOS.