Shiga toxin production and translocation during microaerobic human colonic infection with Shiga toxin-producing E. coli O157:H7 and O104:H4

Haemolytic uraemic syndrome caused by Shiga toxin-producing E. coli (STEC) is dependent on release of Shiga toxins (Stxs) during intestinal infection and subsequent absorption into the bloodstream. An understanding of Stx-related events in the human gut is limited due to lack of suitable experimental models. In this study, we have used a vertical diffusion chamber system with polarized human colon carcinoma cells to simulate the microaerobic (MA) environment in the human intestine and investigate its influence on Stx release and translocation during STEC O157:H7 and O104:H4 infection. Stx2 was the major toxin type released during infection. Whereas microaerobiosis significantly reduced bacterial growth as well as Stx production and release into the medium, Stx translocation across the epithelial monolayer was enhanced under MA versus aerobic conditions. Increased Stx transport was dependent on STEC infection and occurred via a transcellular pathway other than macropinocytosis. While MA conditions had a similar general effect on Stx release and absorption during infection with STEC O157:H7 and O104:H4, both serotypes showed considerable differences in colonization, Stx production, and Stx translocation which suggest alternative virulence strategies. Taken together, our study suggests that the MA environment in the human colon may modulate Stx-related events and enhance Stx absorption during STEC infection

The role of comparative city policy data in assessing progress toward the urban SDG targets

As part of the UN Sustainable Development Goals, all countries have agreed to“make cities and human set-tlements inclusive, safe, resilient and sustainable”. We argue that there is a critical need for large-scale com-parative city policy data that, when linked with outcome data, could be used to identify where policies areworking and where they could be improved. In an assessment of the landscape of existing city policy data, basedon a comprehensive scoping review, wefind that existing databases are insufficient for the purposes of com-parative analysis. We then describe what an“ideal”city policy database would look like, where it could behoused, and how it could be developed. Such a database could be a key tool for achieving SDG 11, the urbanSustainable Development Go

Shiga toxin 2 translocation across intestinal epithelium is linked to virulence of Shiga toxin-producing Escherichia coli in humans

Shiga toxin-producing Escherichia coli (STEC) are characterized by the release of potent Shiga toxins (Stx), which are associated with severe intestinal and renal disease. Although all STEC strains produce Stx, only a few serotypes cause infection in humans. To determine which virulence traits in vitro are linked to human disease in vivo, 13 Stx2a-producing STEC strains of seropathotype (SPT) A or B (associated with severe human intestinal disease and outbreaks) and 6 strains of SPT D or E (rarely or not linked to human disease) were evaluated in a microaerobic human colonic epithelial infection model. All SPT strains demonstrated similar growth, colonization of polarized T84 colon carcinoma cells and Stx release into the medium. In contrast, Stx translocation across the T84 cell monolayer was significantly lower in SPT group DE compared to SPT group AB strains. Further experiments showed that Stx penetration occurred via a transcellular pathway and was independent of bacterial type III secretion and attaching and effacing lesion formation. These results suggest that the extent of Stx transcytosis across the gut epithelium may represent an important indicator of STEC pathogenicity for humans

Primary care treatment of insomnia: study protocol for a pragmatic, multicentre, randomised controlled trial comparing nurse-delivered sleep restriction therapy to sleep hygiene (the HABIT trial).

Introduction Insomnia is a prevalent sleep disorder that negatively affects quality of life. Multicomponent cognitive-behavioural therapy (CBT) is the recommended treatment but access remains limited, particularly in primary care. Sleep restriction therapy (SRT) is one of the principal active components of CBT and could be delivered by generalist staff in primary care. The aim of this randomised controlled trial is to establish whether nurse-delivered SRT for insomnia disorder is clinically and cost-effective compared with sleep hygiene advice. Methods and analysis In the HABIT (Health-professional Administered Brief Insomnia Therapy) trial, 588 participants meeting criteria for insomnia disorder will be recruited from primary care in England and randomised (1:1) to either nurse-delivered SRT (plus sleep hygiene booklet) or sleep hygiene booklet on its own. SRT will be delivered over 4 weekly sessions; total therapy time is approximately 1 hour. Outcomes will be collected at baseline, 3, 6 and 12 months post-randomisation. The primary outcome is self-reported insomnia severity using the Insomnia Severity Index at 6 months. Secondary outcomes include health-related and sleep-related quality of life, depressive symptoms, use of prescribed sleep medication, diary and actigraphy-recorded sleep parameters, and work productivity. Analyses will be intention-to-treat. Moderation and mediation analyses will be conducted and a cost-utility analysis and process evaluation will be performed. Ethics and dissemination Ethical approval was granted by the Yorkshire and the Humber - Bradford Leeds Research Ethics Committee (reference: 18/YH/0153). We will publish our primary findings in high-impact, peer-reviewed journals. There will be further outputs in relation to process evaluation and secondary analyses focussed on moderation and mediation. Trial results could make the case for the introduction of nurse-delivered sleep therapy in primary care, increasing access to evidence-based treatment for people with insomnia disorder

Supporting people with type 2 diabetes diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D pilot): results of a feasibility randomised trial

Background:The purpose of this 6-month intervention pilot feasibility randomised trial was to test sending brief messages using mobile phones to promote self-management through taking medication as prescribed to people with type 2 diabetes. This was to inform the design and conduct of a future large-scale United Kingdom based clinical trial and establish feasibility of recruitment, the technology used, follow up, and data collection. Methods: A multicentre individually randomised, controlled parallel group trial in primary care, recruiting adults (≥35 years) with type 2 diabetes in England. Consenting participants were randomly allocated to receive short message system text-messages up to four times a week, or usual care, for a period of six months; messages contained behavioural change techniques targeting medication use. The primary outcome was the rate of recruitment to randomisation of participants to the trial with a planned rate of 22 participants randomised per month. The study also aimed to establish feasibility of follow up at 6-months, with an aim of retaining more than 80% of participants. Data, including patient reported measures, were collected at baseline and the end of the 6-month follow-up period, and a notes review was completed at 24 months. Results: The trial took place between 26 November 2018 and 30 September 2019. In total 209 participants were randomly allocated to intervention (n=103) or usual care (n=106). The maximum rate of monthly recruitment to the trial was 60-80 participants per month. In total, 12,734 messages were sent to participants. Of these messages, 47 were identified as having failed to be sent by the service provider. Participants sent 2,864 messages to the automated messaging system. Baseline data from medical records were available for >90% of participants with the exception of cholesterol (78.9%). At six months, a further HbA1c measurement was reported for 67% of participants. In total medical record data were available at six-months for 207 (99.0%) of participants and completed self-report data were available for 177 (84.7%) of participants. Conclusion: The feasibility of a large-scale randomised evaluation of brief message intervention for people with type 2 diabetes appears to be high using this efficient design. Failure rate of sending messages is low, rapid recruitment was achieved among people with type 2 diabetes, clinical data is available on participants from routine medical records and self-report of economic measures was acceptable

Nurse-delivered sleep restriction therapy in primary care for adults with insomnia disorder: a mixed-methods process evaluation

Background Sleep restriction therapy (SRT) is a behavioural therapy for insomnia. Aim To conduct a process evaluation of a randomised controlled trial comparing SRT delivered by primary care nurses plus a sleep hygiene booklet with the sleep hygiene booklet only for adults with insomnia disorder. Design and setting A mixed-methods process evaluation in a general practice setting. Method Semi-structured interviews were conducted in a purposive sample of patients receiving SRT, the practice nurses who delivered the therapy, and also GPs or practice managers at the participating practices. Qualitative data were explored using framework analysis, and integrated with nurse comments and quantitative data, including baseline Insomnia Severity Index score and serial sleep efficiency outcomes to investigate the relationships between these. Results In total, 16 patients, 13 nurses, six practice managers, and one GP were interviewed. Patients had no previous experience of behavioural therapy, needed flexible appointment times, and preferred face-to-face consultations; nurses felt prepared to deliver SRT, accommodating patient concerns, tailoring therapy, and negotiating sleep timings despite treatment complexity and delays between training and intervention delivery. How the intervention produced change was explored, including patient and nurse interactions and patient responses to SRT. Difficulties maintaining SRT, negative attitudes towards treatment, and low self-efficacy were highlighted. Contextual factors, including freeing GP time, time constraints, and conflicting priorities for nurses, with suggestions for alternative delivery options, were raised. Participants who found SRT a positive process showed improvements in sleep efficiency, whereas those who struggled did not. Conclusion SRT was successfully delivered by practice nurses and was generally well received by patients, despite some difficulties delivering and applying the intervention in practice

The Grizzly, April 14, 1998

The Poetry of an Outlaw • Ursinus Grad Makes it Big • Opinion: Change Ursinus, Change Yourself • Letter to the Editor • Coontz Lectures at Ursinus • Ursinus Gets Involved with Habitat for Humanity • Not Too Late to Sign-Up for Spring Service Day • The Class of \u2799 Hosts Third Annual Wingbowl • And the Winner of Mr. Ursinus 1998 Is... • The End of Lollapalooza? • Diversity Week at Ursinus • UC Women\u27s Lacrosse Team Battles for Second Place in Conference • UC Softball Sweeps Washington • Ursinus Golf Suffers 1st Defeat in Three Years • Women\u27s Tennis Team Heads in Positive Direction • UC Baseball Remains Tied for Second • Track Runs Strong Against Tough Competitionhttps://digitalcommons.ursinus.edu/grizzlynews/1419/thumbnail.jp

What outcomes are important to patients with mild cognitive impairment or Alzheimer's disease, their caregivers, and health-care professionals? A systematic review

Introduction: Clinical trials involving patients with Alzheimer’s disease (AD) continue to try to identify disease-modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. Methods: A systematic review sought research that elicited information from people with AD, their caregivers, and health-care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Results: Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Discussion: Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.</br

Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D pilot): results of a feasibility randomised trial

Background The purpose of this 6-month intervention pilot feasibility randomised trial was to test sending brief messages using mobile phones to promote self-management through taking medication as prescribed to people with type 2 diabetes. This was to inform the design and conduct of a future large-scale United Kingdom-based clinical trial and establish the feasibility of recruitment, the technology used, follow-up, and data collection. Methods A multicentre individually randomised, controlled parallel group trial in primary care, recruiting adults (≥ 35 years) with type 2 diabetes in England. Consenting participants were randomly allocated to receive short message system text messages up to four times a week, or usual care, for a period of 6 months; messages contained behavioural change techniques targeting medication use. The primary outcome was the rate of recruitment to randomisation of participants to the trial with a planned rate of 22 participants randomised per month. The study also aimed to establish the feasibility of follow-up at 6 months, with an aim of retaining more than 80% of participants. Data, including patient-reported measures, were collected at baseline and the end of the 6-month follow-up period, and a notes review was completed at 24 months. Results The trial took place between 26 November 2018 and 30 September 2019. In total 209 participants were randomly allocated to intervention (n = 103) or usual care (n = 106). The maximum rate of monthly recruitment to the trial was 60–80 participants per month. In total, 12,734 messages were sent to participants. Of these messages, 47 were identified as having failed to be sent by the service provider. Participants sent 2,864 messages to the automated messaging system. Baseline data from medical records were available for > 90% of participants with the exception of cholesterol (78.9%). At 6 months, a further HbA1c measurement was reported for 67% of participants. In total medical record data were available at 6 months for 207 (99.0%) of participants and completed self-report data were available for 177 (84.7%) of participants. Conclusion The feasibility of a large-scale randomised evaluation of brief message intervention for people with type 2 diabetes appears to be high using this efficient design. Failure rate of sending messages is low, rapid recruitment was achieved among people with type 2 diabetes, clinical data is available on participants from routine medical records and self-report of economic measures was acceptable. Trial registration ISCTRN ISRCTN13404264. Registered on 10 October 2018