Identification and characterisation of enteroaggregative Escherichia coli subtypes associated with human disease

Enteroaggregative E. coli (EAEC) are a major cause of diarrhoea worldwide. Due to their heterogeneity and carriage in healthy individuals, identification of diagnostic virulence markers for pathogenic strains has been difficult. In this study, we have determined phenotypic and genotypic differences between EAEC strains of sequence types (STs) epidemiologically associated with asymptomatic carriage (ST31) and diarrhoeal disease (ST40). ST40 strains demonstrated significantly enhanced intestinal adherence, biofilm formation, and pro-inflammatory interleukin-8 secretion compared with ST31 isolates. This was independent of whether strains were derived from diarrhoea patients or healthy controls. Whole genome sequencing revealed differences in putative virulence genes encoding aggregative adherence fimbriae, E. coli common pilus, flagellin and EAEC heat-stable enterotoxin 1. Our results indicate that ST40 strains have a higher intrinsic potential of human pathogenesis due to a specific combination of virulence-related factors which promote host cell colonization and inflammation. These findings may contribute to the development of genotypic and/or phenotypic markers for EAEC strains of high virulence

Development of a novel human intestinal model to elucidate the effect of anaerobic commensals on Escherichia coli infection

The gut microbiota plays a crucial role in protecting against enteric infection. However, the underlying mechanisms are largely unknown due to a lack of suitable experimental models. Whilst most gut commensals are anaerobic, intestinal epithelial cells require oxygen for survival. In addition, most intestinal cell lines do not produce mucus which provides a habitat for the microbiota. Here, we have developed a microaerobic, mucus-producing vertical diffusion chamber (VDC) model and determined the influence of Limosilactobacillus reuteri and Ruminococcus gnavus on enteropathogenic E. coli (EPEC) infection. Optimization of the culture medium enabled bacterial growth in the presence of mucus-producing T84/LS174T cells. While L. reuteri diminished EPEC growth and adhesion to T84/LS174T and mucus-deficient T84 epithelia, R. gnavus only demonstrated a protective effect in the presence of LS174T cells. Reduced EPEC adherence was not associated with altered type III secretion pore formation. In addition, co-culture with L. reuteri and R. gnavus dampened EPEC-induced interleukin-8 secretion. The microaerobic mucin-producing VDC system will facilitate investigations into the mechanisms underpinning colonization resistance and aid the development of microbiota-based anti-infection strategies

Evaluating the feasibility of implementing a Telesleep pilot program using two-tiered external facilitation

Background: Obstructive sleep apnea (OSA) can negatively impact patients' health status and outcomes. Positive airway pressure (PAP) reverses airway obstruction and may reduce the risk of adverse outcomes. Remote monitoring of PAP (as opposed to in-person visits) may improve access to sleep medicine services. This study aimed to evaluate the feasibility of implementing a clinical program that delivers treatment for OSA through PAP remote monitoring using external facilitation as an implementation strategy. Methods: Participants included patients with OSA at a Veteran Affairs Medical Center (VAMC). PAP adherence and clinical disease severity on treatment (measured by the apnea hypopnea index [AHI]) were the preliminary effectiveness outcomes across two delivery models: usual care (in-person) and Telehealth nurse-delivered remote monitoring. We also assessed visit duration and travel distance. A prospective, mixed-methods evaluation examined the two-tiered external facilitation implementation strategy. Results: The pilot project included N = 52 usual care patients and N = 38 Telehealth nurse-delivered remote monitoring patients. PAP adherence and disease severity were similar across the delivery modalities. However, remote monitoring visits were 50% shorter than in-person visits and saved a mean of 72 miles of travel (median = 45.6, SD = 59.0, mode = 17.8, range 5.4-220). A total of 62 interviews were conducted during implementation with a purposive sample of 12 clinical staff involved in program implementation. Weekly external facilitation delivered to both front-line staff and supervisory physicians was necessary to ensure patient enrollment and treatment. Synchronized, "two-tiered" facilitation at the executive and coordinator levels proved crucial to developing the clinical and administrative infrastructure to support a PAP remote monitoring program and to overcome implementation barriers. Conclusions: Remote PAP monitoring had similar efficacy to in-person PAP services in this Veteran population. Although external facilitation is a widely-recognized implementation strategy in quality improvement projects, less is known about how multiple facilitators work together to help implement complex programs. Two-tiered facilitation offers a model well-suited to programs where innovations span disciplines, disrupt professional hierarchies (such as those between service chiefs, clinicians, and technicians) and bring together providers who do not know each other, yet must collaborate to improve access to care

Activated gliosis, accumulation of amyloid β, and hyperphosphorylation of tau in aging canines with and without cognitive decline

Canine cognitive dysfunction (CCD) syndrome is a well-recognized naturally occurring disease in aged dogs, with a remarkably similar disease course, both in its clinical presentation and neuropathological changes, as humans with Alzheimer’s disease (AD). Similar to human AD patients this naturally occurring disease is found in the aging canine population however, there is little understanding of how the canine brain ages pathologically. It is well known that in neurodegenerative diseases, there is an increase in inflamed glial cells as well as an accumulation of hyperphosphorylation of tau (P-tau) and amyloid beta (Aβ1-42). These pathologies increase neurotoxic signaling and eventual neuronal loss. We assessed these brain pathologies in aged canines and found an increase in the number of glial cells, both astrocytes and microglia, and the activation of astrocytes indicative of neuroinflammation. A rise in the aggregated protein Aβ1-42 and hyperphosphorylated tau, at Threonine 181 and 217, in the cortical brain regions of aging canines. We then asked if any of these aged canines had CCD utilizing the only current diagnostic, owner questionnaires, verifying positive or severe CCD had pathologies of gliosis and accumulation of Aβ1-42 like their aged, matched controls. However uniquely the CCD dogs had P-tau at T217. Therefore, this phosphorylation site of tau at threonine 217 may be a predictor for CCD

Vocational education and training for African development: a literature review

© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. The SDGs mark the clearest global acceptance yet that the previous approach to development was unsustainable. In VET, UNESCO has responded by developing a clear account of how a transformed VET must be part of a transformative approach to development. It argues that credible, comprehensive skills systems can be built that can support individuals, communities, and organisations to generate and maintain enhanced and just livelihood opportunities. However, the major current theoretical approaches to VET are not up to this challenge. In the context of Africa, we seek to address this problem through a presentation of literatures that contribute to the theorisation of this new vision. They agree that the world is not made up of atomised individuals guided by a “hidden hand”. Rather, reality is heavily structured within political economies that have emerged out of contestations and compromises in specific historical and geographical spaces. Thus, labour markets and education and training systems have arisen, characterised by inequalities and exclusions. These specific forms profoundly influence individuals’ and communities’ views about the value of different forms of learning and working. However, they do not fully define what individuals dream, think and do. Rather, a transformed and transformative VET for Africa is possible

Transitioning Vocational Education and Training in Africa

EPDF and EPUB available Open Access under CC-BY-NC-ND licence. This book takes an expansive view of vocational education and training. Drawing on case studies across rural and urban settings in Uganda and South Africa, the book offers a new way of seeing this through an exploration of the multiple ways in which people learn to have better livelihoods. Crucially, it explores learning that takes place informally online, within farmers’ groups and in public and private education institutions

The structural basis of bacterial manganese import

肺炎球菌が細胞内にマンガンイオンを取り込むしくみ --膜輸送体PsaBCの立体構造の解明--. 京都大学プレスリリース. 2021-09-15.Metal ions are essential for all forms of life. In prokaryotes, ATP-binding cassette (ABC) permeases serve as the primary import pathway for many micronutrients including the first-row transition metal manganese. However, the structural features of ionic metal transporting ABC permeases have remained undefined. Here, we present the crystal structure of the manganese transporter PsaBC from Streptococcus pneumoniae in an open-inward conformation. The type II transporter has a tightly closed transmembrane channel due to “extracellular gating” residues that prevent water permeation or ion reflux. Below these residues, the channel contains a hitherto unreported metal coordination site, which is essential for manganese translocation. Mutagenesis of the extracellular gate perturbs manganese uptake, while coordination site mutagenesis abolishes import. These structural features are highly conserved in metal-specific ABC transporters and are represented throughout the kingdoms of life. Collectively, our results define the structure of PsaBC and reveal the features required for divalent cation transport