A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency.

Background: Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management.

Objectives: To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK.

Amyotrophic Lateral Sclerosis-Associated Persistent Organic Pollutant -Chlordane Causes GABA-Independent Toxicity to Motor Neurons, Providing Evidence toward an Environmental Component of Sporadic Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the death of upper and lower motor neurons. While causative genes have been identified, 90% of ALS cases are not inherited and are hypothesized to result from the accumulation of genetic and environmental risk factors. While no specific causative environmental toxin has been identified, previous work has indicated that the presence of the organochlorine pesticide chlordane in the blood is highly correlated with ALS incidence.

Impact of COVID-19-associated anxiety on the adherence to intravitreal injection in patients with macular diseases a year after the initial outbreak.

Background: As the primary burden of treating COVID-19 patients began to ease in the United Kingdom, ophthalmology clinic volume within the National Health Service has since recovered. Alarmingly, the rate of non-attendance remains higher than the pre-pandemic level.

Purpose: The purpose was to assess how the perceived risk of contracting coronavirus disease 2019 (COVID-19) influences the willingness of individuals with sight-threatening macular conditions to attend intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection appointments during the second wave of the pandemic.

Silencing the G-protein coupled receptor 3-salt inducible kinase 2 pathway promotes human β cell proliferation.

Loss of pancreatic β cells is the hallmark of type 1 diabetes, for which provision of insulin is the standard of care. While regenerative and stem cell therapies hold the promise of generating single-source or host-matched tissue to obviate immune-mediated complications, these will still require surgical intervention and immunosuppression. Here we report the development of a high-throughput RNAi screening approach to identify upstream pathways that regulate adult human β cell quiescence and demonstrate in a screen of the GPCRome that silencing G-protein coupled receptor 3 (GPR3) leads to human pancreatic β cell proliferation.

Current and emerging treatments for albinism.

Albinism is a group of rare inherited disorders arising from impairment of melanin biosynthesis. The reduction of melanin synthesis leads to hypopigmentation of the skin and eyes. A wide range of ophthalmic manifestations arise from albinism, including reduction of visual acuity, nystagmus, strabismus, iris translucency, foveal hypoplasia, fundus hypopigmentation, and abnormal decussation of retinal ganglion cell axons at the optic chiasm.

Coding and noncoding gene expression biomarkers in mood disorders and schizophrenia.

Mood disorders and schizophrenia are common and complex disorders with consistent evidence of genetic and environmental influences on predisposition. It is generally believed that the consequences of disease, gene expression, and allelic heterogeneity may be partly the explanation for the variability observed in treatment response. Correspondingly, while effective treatments are available for some patients, approximately half of the patients fail to respond to current neuropsychiatric treatments.

Mitochondrial mutations and polymorphisms in psychiatric disorders.

Mitochondrial deficiencies with unknown causes have been observed in schizophrenia (SZ) and bipolar disorder (BD) in imaging and postmortem studies. Polymorphisms and somatic mutations in mitochondrial DNA (mtDNA) were investigated as potential causes with next generation sequencing of mtDNA (mtDNA-Seq) and genotyping arrays in subjects with SZ, BD, major depressive disorder (MDD), and controls. The common deletion of 4,977 bp in mtDNA was compared between SZ and controls in 11 different vulnerable brain regions and in blood samples, and in dorsolateral prefrontal cortex (DLPFC) of BD, SZ, and controls.

Lack of association to a NRG1 missense polymorphism in schizophrenia or bipolar disorder in a Costa Rican population.

A missense polymorphism in the NRG1 gene, Val>Leu in exon 11, was reported to increase the risk of schizophrenia in selected families from the Central Valley region of Costa Rica (CVCR). The present study investigated the relationship between three NRG1 genetic variants, rs6994992, rs3924999, and Val>Leu missense polymorphism in exon 11, in cases and selected controls from an isolated population from the CVCR. Isolated populations can have less genetic heterogeneity and increase power to detect risk variants in candidate genes.

Exon expression in lymphoblastoid cell lines from subjects with schizophrenia before and after glucose deprivation.

Background: The purpose of this study was to examine the effects of glucose reduction stress on lymphoblastic cell line (LCL) gene expression in subjects with schizophrenia compared to non-psychotic relatives.

Methods: LCLs were grown under two glucose conditions to measure the effects of glucose reduction stress on exon expression in subjects with schizophrenia compared to unaffected family member controls. A second aim of this project was to identify cis-regulated transcripts associated with diagnosis.

Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder.

Background: Mitochondria provide most of the energy for brain cells by the process of oxidative phosphorylation. Mitochondrial abnormalities and deficiencies in oxidative phosphorylation have been reported in individuals with schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) in transcriptomic, proteomic, and metabolomic studies. Several mutations in mitochondrial DNA (mtDNA) sequence have been reported in SZ and BD patients.