Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation

Airway inflammation and remodelling are important pathophysiologic features in asthma and other respiratory conditions. An intact epithelial cell layer is crucial to maintain lung homoeostasis, and this depends on intercellular adhesion, whilst damaged respiratory epithelium is the primary instigator of airway inflammation. The Coxsackievirus Adenovirus Receptor (CAR) is highly expressed in the epithelium where it modulates cell-cell adhesion stability and facilitates immune cell transepithelial migration. However, the contribution of CAR to lung inflammation remains unclear. Here we investigate the mechanistic contribution of CAR in mediating responses to the common aeroallergen, House Dust Mite (HDM). We demonstrate that administration of HDM in mice lacking CAR in the respiratory epithelium leads to loss of peri-bronchial inflammatory cell infiltration, fewer goblet-cells and decreased pro-inflammatory cytokine release. In vitro analysis in human lung epithelial cells confirms that loss of CAR leads to reduced HDM-dependent inflammatory cytokine release and neutrophil migration. Epithelial CAR depletion also promoted smooth muscle cell proliferation mediated by GSK3β and TGF-β, basal matrix production and airway hyperresponsiveness. Our data demonstrate that CAR coordinates lung inflammation through a dual function in leucocyte recruitment and tissue remodelling and may represent an important target for future therapeutic development in inflammatory lung diseases

Creative methods: problematics for inquiry and pedagogy in health and social care

This article provides an overview of initial discussions emerging from the Creative Methods Network, an informal organisation concerned with the use of the creative arts in research, teaching and practice in health and social care. Key issues are presented and contextualised with regard to the current conditions in which health and social care research and education is practised. Our own discussions have come to question the seeming dominance of governance within professional education programmes in which there is a primary focus on developing technical skill and capacity. Such governance often extends itself to the measurement of the implementation of these technical skills and this is set against concerns about the absence of creativity and the humanities in the educational programmes of caring for human beings. Consequently, the article reflects a view that the use of the creative arts and humanities in the education of the human caring professions is being eroded away in favour of technical-rational reasoning. It is argued that this then presents an important problem manifested in an emphasis on established and quantifiable knowledge transfer which inhibits other forms of knowledge generation. For the purposes of this discussion we have viewed this problem through the lenses offered by Foucault and Bourdieu

Lived experiences of the diagnostic assessment process for Fetal Alcohol Spectrum Disorder: A systematic review of qualitative evidence

First published: 02 May 2023Early assessment and diagnosis of FASD are crucial in providing therapeutic interventions that aim to enhance meaningful participation and quality of life for individuals and their families, while reducing psychosocial difficulties that may arise during adolescence and adulthood. Individuals with lived experience of FASD have expertise based on their own lives and family needs. Their insights into the assessment and diagnostic process are valuable for improving service delivery and informing the provision of meaningful, person- and family-centered care. To date, reviews have focused broadly on the experiences of living with FASD. The aim of this systematic review is to synthesize qualitative evidence on the lived experiences of the diagnostic assessment process for FASD. Six electronic databases, including PubMed, the Cochrane Library, CINAH, EMBASE, PsycINFO, and Web of Science Core Collection were searched from inception until February 2021, and updated in December 2022. A manual search of reference lists of included studies identified additional studies for inclusion. The quality of included studies was assessed using the Critical Appraisal Skills Program Checklist for Qualitative Studies. Data from included studies were synthesized using a thematic analysis approach. GRADE-CERQual was used to assess confidence in the review findings. Ten studies met the selection criteria for inclusion in the review. Thematic analysis identified 10 first-level themes relating to four over-arching topics: (1) pre-assessment concerns and challenges, (2) the diagnostic assessment process, (3) receipt of the diagnosis, and (4) post-assessment adaptations and needs. GRADECERQual confidence ratings for each of the review themes were moderate to high. The findings from this review have implications for referral pathways, client-centered assessment processes, and post-diagnostic recommendations and support.Nicole Hayes, Kerryn Bagley, Nicole Hewlett, Elizabeth J. Elliott, Carmela F. Pestell, Matthew J. Gullo, Zachary Munn, Philippa Middleton, Prue Walker, Haydn Till, Dianne C. Shanley, Sophia L. Young, Nirosha Boaden, Delyse Hutchinson, Natalie R. Kippin, Amy Finlay- Jones, Rowena Friend, Doug Shelton, Alison Crichton, Natasha Rei

SM-1 (FORMERLY APPR-1) RESEARCH AND DEVELOPMENT PROGRAM INTERIM REPORT ON CORE MEASUREMENTS. Task No. VII

Physics experinments were performed on the SM-1 (formerly APPR-1) core to evaluate temperature and pressure coefficients, transient xenon, neutron source requirements, safety margin, and core reactivity as a function of core life. The temperature coefficient was measured as --3.5 plus or minus 0.13 cents/ deg F at 443 deg F several times throughout life and no change with life time is thus far indicated. The hot to cold reactivity change (440 to 70 deg F) was 6.70 dollars. The pressure coefficient was 1.05 plus or minus 0.05 cents per 100 psi at 115 deg F. Reactivity value for equilibrium xenon was found to be 3.32 dollars and peak xenon reactivity was 4.64 dollars. The 15 curie Po Be source and the beryllium photoneutron source have proved adequate for safe stantup. The safety margin 80% rod insertion'' was found to depend strongly upon the rod configuration. The core reactivity has decreased approximately 5.8 dollars up to 9.1 Mwyr leaving an estimated 5.6 dollars to be used. The core life is expected to be 15 Mwyr. All measurements indicated satisfactory performance of the (SM-1) core. (auth

Mon1a protein acts in trafficking through the secretory apparatus

10.1074/jbc.M112.354043Journal of Biological Chemistry2873025577-25588JBCH