Fever, hyperglycaemia and swallowing dysfunction management in acute stroke: A cluster randomised controlled trial of knowledge transfer

Background: Hyperglycaemia, fever, and swallowing dysfunction are poorly managed in the admission phase of acute stroke, and patient outcomes are compromised. Use of evidence-based guidelines could improve care but have not been effectively implemented. Our study aims to develop and trial an intervention based on multidisciplinary team-building to improve management of fever, hyperglycaemia, and swallowing dysfunction in patients following acute stroke. Methods and design: Metropolitan acute stroke units (ASUs) located in New South Wales, Australia will be stratified by service category (A or B) and, within strata, by baseline patient recruitment numbers (high or low) in this prospective, multicentre, single-blind, cluster randomised controlled trial (CRCT). ASUs then will be randomised independently to either intervention or control groups. ASUs allocated to the intervention group will receive: unit-based workshops to identify local barriers and enablers; a standardised core education program; evidence-based clinical treatment protocols; and ongoing engagement of local staff. Control group ASUs will receive only an abridged version of the National Clinical Guidelines for Acute Stroke Management. The following outcome measures will be collected at 90 days post-hospital admission: patient death, disability (modified Rankin Score); dependency (Barthel Index) and Health Status (SF-36). Additional measures include: performance of swallowing screening within 24 hours of admission; glycaemic control and temperature control. Discussion: This is a unique study of research transfer in acute stroke. Providing optimal inpatient care during the admission phase is essential if we are to combat the rising incidence of debilitating stroke. Our CRCT will also allow us to test interventions focussed on multidisciplinary ASU teams rather than individual disciplines, an imperative of modern hospital services

The autistic brain in the context of normal neurodevelopment

The etiology of autism spectrum disorders (ASD) is complex and largely unclear. Among various lines of inquiry, many have suggested convergence onto disruptions in both neural circuitry and immune regulation/glial cell function pathways. However, the interpretation of the relationship between these two putative mechanisms has largely focused on the role of exogenous factors and insults, such as maternal infection, in generating activating immune pathways that in turn result in neural network abnormalities. Yet, given recent insights in our understanding of human neurodevelopment, and in particular the critical role of glia and the immune system in normal brain development, it is important to consider these putative pathological processes in their appropriate normal neurodevelopmental context. In this review, we explore the hypothesis that the autistic brain cellular phenotype likely represents intrinsic abnormalities of glial/immune processes constitutively operant in normal brain development that result in the observed neural network dysfunction. We review recent studies demonstrating the intercalated role of neural circuit development, the immune system, and glial cells in the normal developing brain, an integrate them with studies demonstrating pathological alterations in these processes in autism. By discussing known abnormalities in the autistic brain in the context of normal brain development, we explore the hypothesis that the glial/immune component of ASD may instead be related to intrinsic exaggerated/abnormal constitutive neurodevelopmental processes such as network pruning. Moreover, this hypothesis may be relevant to other neurodevelopmental disorders that share genetic, pathologic, and clinical features with autism

IRDL Scholars\u27 Speaker Series summary discussion session

This session will offer an opportunity to discuss how the four 2022 presenters’ research and perspectives can make an impact in library and information science research. This session will encourage participation among attendees. The featured speakers of this event are from the 2022 IRDL Scholars’ Speaker Series Organizing Committee: Catherine Baird, Hilary Bussell, Michael Flierl, Rosalinda Linares, Catherine Meals, Leatha Miles-Edmonson, Sophie Rondeau, Dana Statton Thompson.https://digitalcommons.lmu.edu/irdl-speakerseries-2022/1004/thumbnail.jp

Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging

Werner syndrome (WS) patients exhibit premature aging predominantly in mesenchyme-derived tissues, but not in neural lineages, a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here, we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging, we differentiated iPSCs to mesenchymal stem cells (MSCs) and neural stem/progenitor cells (NPCs). We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs, but not in NPCs. We postulate this “aging” discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized NPCs to DNA damage. Our findings unveil a role for telomerase in the protection of accelerated aging in a specific lineage of stem cells

Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium