Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

Background: Although chloroquine, hydroxychloroquine, and quinine are used for a range of medical conditions, recent research suggested a potential role in treating COVID-19. The resultant increase in prescribing was accompanied by an increase in adverse events, including severe toxicity and death. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup sought to determine the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs.

Genetic Analysis of in an Early-Onset Parkinson's Disease Cohort.

Pathogenic variants in the gene encoding RAB39B, resulting in the loss of protein function, lead to the development of X-linked early-onset parkinsonism. The gene is located within a chromosomal region that is susceptible to genomic rearrangement, and while an increased dosage of was previously associated with cognitive impairment, the potential role of dosage alterations in Parkinson's disease (PD) remains to be determined. This study aimed to investigate the contribution of the genetic variation in RAB39B to the development of early-onset PD.

Distribution of Parkinson's disease associated RAB39B in mouse brain tissue.

Pathogenic variants in the gene encoding the small GTPase Ras analogue in Brain 39b (RAB39B) are associated with early-onset parkinsonism. In this study we investigated the expression and localization of RAB39B (RNA and protein) in mouse brain tissue to gain a better understanding of its normal physiological function(s) and role in disease.We developed novel resources, including monoclonal antibodies directed against RAB39B and mice with Rab39b knockout, and performed real-time PCR and western blot analysis on whole brain lysates.

Digital Health Solutions for Indigenous Mental Well-Being.

Purpose Of Review: This review summarizes digital health solutions being used for Indigenous mental well-being, with emphasis on available evidence and examples reported in the literature. We also describe our own local experience with a rural telemental health service for Indigenous youth and discuss the unique opportunities and challenges.

Recent Findings: Digital health solutions can be grouped into three main categories: (1) remote access to specialists, (2) building and supporting local capacity, and (3) patient-directed interventions.

Familial early onset Parkinson's disease caused by a homozygous frameshift variant in PARK7: Clinical features and literature update.

Background: Bi-allelic mutations in PARK7 are a rare cause of autosomal recessive early onset Parkinson's disease (EO-PD). To date, 30 individuals harbouring 20 unique causative variants have been described. Understanding of the spectrum of clinical features and natural history of PARK7 mediated EO-PD remain limited.

Generation of RAB39B knockout isogenic human embryonic stem cell lines to model RAB39B-mediated Parkinson's disease.

Mutations in RAB39B are a known cause of X-linked early onset Parkinson's disease. Isogenic human embryonic stem cell lines carrying two independent deletions of RAB39B were generated using CRISPR/Cas9 genome editing tool. The deletions were confirmed by PCR and direct sequence analysis in two edited stem cell lines.

The emerging role of Rab GTPases in the pathogenesis of Parkinson's disease.

The identification of pathogenic mutations in Ras analog in brain 39B (RAB39B) and Ras analog in brain 32 (RAB32) that cause Parkinson's disease (PD) has highlighted the emerging role of protein trafficking in disease pathogenesis. Ras analog in brain (Rab) Guanosine triphosphatase (GTPase) function as master regulators of membrane trafficking, including vesicle formation, movement along cytoskeletal networks, and membrane fusion. Recent studies have linked Rab GTPases with α-synuclein, Leucine-rich repeat kinase 2, and Vacuolar protein sorting 35, 3 key proteins in PD pathogenesis.

ALPK3-deficient cardiomyocytes generated from patient-derived induced pluripotent stem cells and mutant human embryonic stem cells display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy.

Aims: We identified a novel homozygous truncating mutation in the gene encoding alpha kinase 3 (ALPK3) in a family presenting with paediatric cardiomyopathy. A recent study identified biallelic truncating mutations of ALPK3 in three unrelated families; therefore, there is strong genetic evidence that ALPK3 mutation causes cardiomyopathy. This study aimed to clarify the mutation mechanism and investigate the molecular and cellular pathogenesis underlying ALPK3-mediated cardiomyopathy.

Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology.

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.

Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.

Background: Mutations in genes encoding components of the Brahma-associated factor (BAF) chromatin remodeling complex have recently been shown to contribute to multiple syndromes characterised by developmental delay and intellectual disability. ARID1B mutations have been identified as the predominant cause of Coffin-Siris syndrome and have also been shown to be a frequent cause of nonsyndromic intellectual disability. Here, we investigate the molecular basis of a patient with an overlapping but distinctive phenotype of intellectual disability, plantar fat pads and facial dysmorphism.

Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome.

Borrone Dermato-Cardio-Skeletal (BDCS) syndrome is a severe progressive autosomal recessive disorder characterized by coarse facies, thick skin, acne conglobata, dysmorphic facies, vertebral abnormalities and mitral valve prolapse. We identified a consanguineous kindred with a child clinically diagnosed with BDCS. Linkage analysis of this family (BDCS1) identified five regions homozygous by descent with a maximum LOD score of 1.

Prison inmates' views of whether reporting rape is the same as snitching: an exploratory study and research agenda.

Although the prevalence of sexual assault in U.S. prisons is debated, it is known that the consequences for victims can be quite severe.

ironXS: high-school screening for hereditary haemochromatosis is acceptable and feasible.

As the results of the Human Genome Project are realised, screening for genetic mutations that predispose to preventable disease is becoming increasingly possible. How and where such screening should best be offered are critical, unanswered questions. This study aimed to assess the acceptability and feasibility of genetic screening for preventable disease, using the model of hereditary haemochromatosis, in high-school students.

Deletion of the Parkin co-regulated gene causes defects in ependymal ciliary motility and hydrocephalus in the quakingviable mutant mouse.

The quakingviable mouse (qkv) is a spontaneous recessive mouse mutant with a deletion of approximately 1.1 Mb in the proximal region of chromosome 17. The deletion affects the expression of three genes; quaking (Qk), Parkin-coregulated gene (Pacrg) and parkin (Park2).

Expression and localization of the Parkin co-regulated gene in mouse CNS suggests a role in ependymal cilia function.

Parkin Co-Regulated Gene (PACRG) is a gene that shares a bi-directional promoter with the Parkinson's disease associated gene parkin. The functional role of PACRG is not well understood, although the gene has been associated with parkinsonian syndromes and more recently with eukaryotic cilia and flagella. We investigated the expression of Pacrg in the mouse brain by in situ hybridization and observed robust expression of Pacrg in the cells associated with the lateral, third and fourth ventricle, in addition to the aqueduct of Sylvius and choroid plexus.

Molecular analysis of the PArkin co-regulated gene and association with male infertility.

Objective: To investigate the potential role of PArkin co-regulated gene (PACRG) in human male infertility.

Design: Case-control study.

Setting: Academic reproductive biology department.

Regional and cellular localisation of Parkin co-regulated gene in developing and adult mouse brain.

Parkin Co-Regulated Gene (PACRG) is a novel gene that is oriented in a head-to-head array with parkin, and expression of the two genes is regulated by a shared bi-directional promoter. Mutations in parkin are the most common cause of early-onset autosomal recessive Parkinson's disease, however the function of PACRG and potential role in the pathogenesis of Parkinson's disease are unclear. We generated polyclonal anti-PACRG antisera and performed immunohistochemical analysis of the regional and temporal distribution of Pacrg in the mouse brain.

IL-12p40 and IL-18 in crescentic glomerulonephritis: IL-12p40 is the key Th1-defining cytokine chain, whereas IL-18 promotes local inflammation and leukocyte recruitment.

Experimental crescentic glomerulonephritis (GN) is characterized by T helper 1 (Th1) directed nephritogenic immune responses and cell-mediated glomerular injury. IL-12p40, the common cytokine chain for both IL-12 and IL-23, is important in the generation and potentially the maintenance of Th1 responses, whereas IL-18 is a co-factor for Th1 responses that may have systemic and local proinflammatory effects. For testing the hypothesis that both endogenous IL-12p40 and endogenous IL-18 play pathogenetic roles in crescentic GN, accelerated anti-glomerular basement membrane GN was induced in mice genetically deficient in IL-12p40 (IL-12p40-/-), IL-18 (IL-18-/-), or both IL-12p40 and IL-18 (IL-12p40-/-IL-18-/-).

Experimental autoimmune Goodpasture's disease: a pathogenetic role for both effector cells and antibody in injury.

Background: Goodpasture's disease [antiglomerular basement membrane (GBM) glomerulonephritis] is a classic autoimmune disease and the only organ-specific autoimmune renal disease in which the antigen is well described. The importance of antibodies against the non-collagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] is well established. However, observational human studies and studies in experimental systems also imply a role for cell-mediated effector injury.

Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: a protective role for IFN-gamma.

IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers.