The Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis cohort population structure and disease etiology.

Background: Previous genetic and epidemiological studies have examined subpopulations from the Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (CCPGSMS) patient cohort, but an encompassing analysis of the study population has not yet been carried out.

Objective: This study examines patterns of multiple sclerosis (MS) prevalence in 13,663 cohort members, including 4,821 patients with MS or suspected MS and 8,842 family members.

Methods: We grouped participants into epidemiologic subgroups based on age of MS onset, clinical stage at diagnosis, symptom type at disease onset, sex, proband status, disability as measured by the EDSS, and ancestry based on reported ethnicity.

HLA-B gene methylation and expression in Behçet's syndrome: a potential role of epigenetics in the pathogenesis.

Objectives: The HLA-B51 locus has the strongest association with Behçet's syndrome (BS). The presence of a CpG island in the HLA-B gene led us to examine the role of epigenetic regulation in BS.

Methods: HLA-B51 genotyping was performed via sequence-specific PCR in 15 index familial BS cases, 17 affected relatives, 26 unaffected relatives, 46 sporadic BS cases, and 41 healthy controls.

A Case of Coexistent Spinocerebellar Ataxia Type 2 and Primary Progressive Multiple Sclerosis-Coincidental or Associated?

Spinocerebellar ataxia type 2 (SCA2) is a dominantly inherited ataxia primarily characterised by progressive cerebellar syndrome, which is developed due to the expansion of the CAG trinucleotide repeat within the first exon of the ATXN2 gene. We report a rare case of a 41-year-old woman with coexistent genetically verified SCA2 and primary progressive multiple sclerosis (MS). Considering our case and a few others reported in the literature, as well as a possible genetic association between ATXN2 and MS susceptibility, we suggest that the coexistence of SCA and MS may not be coincidental, especially in patients with a progressive MS course.

Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement.

Prospective outcome analysis of multiple sclerosis cases reveals candidate prognostic cerebrospinal fluid markers.

Background: Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging.

Objective: We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.

Comparison of multiple sclerosis patients with or without rebound activity after fingolimod cessation: Five-year clinical outcomes.

Background: Patients with multiple sclerosis (MS) who discontinue fingolimod might present with rebound activity. The reasons for the development of rebound have been identified, but there are limited data on the long-term clinical outcomes of these patients. This study aimed to compare the long-term outcomes of patients with MS with and without rebound activity after fingolimod discontinuation.

Detection of a rare variant in PSTPIP1 through three generations in a family with an initial diagnosis of FMF/MKD-overlapping phenotype.

Objective: The presence of FMF cases without MEFV (MEFV innate immunity regulator, pyrin) pathogenic variants led us to search for other genes' involvement in the disease development. Here, we describe the presence of genetic heterogeneity in a three-generation family with an FMF/mevalonate kinase deficiency (MKD)-overlapping phenotype without MEFV/MVK (mevalonate kinase) pathogenic variants.

Method: Targeted sequencing revealed a rare, fully penetrant variant in PSTPIP1 (p.

Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation.

Many multiple sclerosis (MS)-associated common risk variants as well as candidate low-frequency and rare variants have been identified; however, approximately half of MS heritability remains unexplained. We studied seven multiplex MS families, six of which with parental consanguinity, to identify genetic factors that increase MS risk. Candidate genomic regions were identified through linkage analysis and homozygosity mapping, and fully penetrant, rare, and low-frequency variants were detected by exome sequencing.

MYO1H is a novel candidate gene for autosomal dominant pure hereditary spastic paraplegia.

In this study, we aimed to determine the genetic basis of a Turkish family related to hereditary spastic paraplegia (HSP) by exome sequencing. HSP is a progressive neurodegenerative disorder and displays genetic and clinical heterogeneity. The major symptoms are muscle weakness and spasticity, especially in the lower extremities.

Increasing ICU capacity to accommodate higher demand during the COVID-19 pandemic.

Objectives: To describe the short term ability of Australian intensive care units (ICUs) to increase capacity in response to heightened demand caused by the COVID-19 pandemic.

Design: Survey of ICU directors or delegated senior clinicians (disseminated 30 August 2021), supplemented by Australian and New Zealand Intensive Care Society (ANZICS) registry data.

Setting: All 194 public and private Australian ICUs.

Investigation of multiple sclerosis-related pathways through the integration of genomic and proteomic data.

Background: Multiple sclerosis (MS) has a complex pathophysiology, variable clinical presentation, and unpredictable prognosis; understanding the underlying mechanisms requires combinatorial approaches that warrant the integration of diverse molecular omics data.

Methods: Here, we combined genomic and proteomic data of the same individuals among a Turkish MS patient group to search for biologically important networks. We previously identified differentially-expressed proteins by cerebrospinal fluid proteome analysis of 179 MS patients and 42 non-MS controls.

ICU shift related effects on sleep, fatigue and alertness levels.

Background: Shift work may lead to suboptimal sleep resulting in impaired alertness, and lowered performance levels, all of which can lead to medical errors.

Aims: To examine fatigue, sleepiness and behavioural alertness prospectively in a tertiary level Australian intensive care unit (ICU).

Methods: All full-time doctors providing 24-h resident cover on a 12-h day and 12-h night shift roster were invited to participate in this study.

Correction to: Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study.

The second affiliation of the corresponding author Eda Tahir Turanlı was incorrectly published as İstanbul Medeniyet University instead of Istanbul Technical University.

Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study.

Systemic autoinflammatory diseases (sAIDs) are a heterogeneous group of disorders, having monogenic inherited forms with overlapping clinical manifestations. More than half of patients do not carry any pathogenic variant in formerly associated disease genes. Here, we report a cross-sectional study on targeted Next-Generation Sequencing (NGS) screening in patients with suspected sAIDs to determine the diagnostic utility of genetic screening.

Role of genetics in pediatric rheumatology.

Pediatric rheumatology includes autoinflammatory monogenic diseases, autoinflammatory multifactorial diseases with complex inheritance, and diseases with uncertain clinical diagnosis or undefined conditions, even though they show signs of autoinflammation. Most of these diseases are systemic; it is important to diagnose patients promptly and definitively and to select proper treatment options based on the diagnoses. Clinical observation and acute-phase responses are usually sufficient for diagnosis; however, genetic analyses can provide supportive data for definite diagnosis and treatment, especially for rare monogenic diseases.

Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models.

The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models.

Neurotoxicity with persistent unilateral ophthalmoplegia from envenoming by a wild inland taipan (Oxyuranus microlepidotus, Elapidae) in remote outback South Australia.

Introduction: A case of life threatening envenoming by a wild specimen of the inland taipan, Oxyuranus microlepidotus, is described. There have been 11 previously well-documented envenomings by O. microlepidotus, but only 2 were inflicted by wild snakes.

Effectiveness of Shared Medical Appointments Versus Traditional Clinic Visits for Adolescents With Type 1 Diabetes.

Shared medical appointments began in the United States in 1996 to advance quality of care and enhance patients' ability to self-manage. Group visits gather patients with the same diagnosis for individual examinations followed by group education sessions taught by the provider. This leads to the opportunity to learn from the experiences of others.

45,X/47,XXX Mosaicism and Short Stature.

We describe the case of a ten-year-old girl with short stature and 45,X/47,XXX genotype. She also suffered from vesicoureteric reflux and kidney dysfunction prior to having surgery on her ureters. Otherwise, she does not have any of the characteristics of Turner nor Triple X syndrome.

Postinjection Muscle Fibrosis from Lupron.

We describe the case of a 6.5-year-old girl with central precocious puberty (CPP), which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP.

Utility of atrial temporary pacing as an acute treatment for bradyarrhythmias and tachyarrhythmias in the intensive care setting with preservation of atrioventricular synchrony.

Temporary pacing is often used as an acute treatment of bradyarrhythmias and suppression of tachyarrhythmias. In patients with cardiogenic shock, loss of atrioventricular synchrony may worsen cardiovascular haemodynamics. We present a series where temporary right atrial pacing was used as an acute treatment for both bradyarrhythmias and tachyarrhythmias.