Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction

Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia. During infection, V. parahaemolyticus primarily attaches to the small intestine, where it causes extensive tissue damage and compromises epithelial barrier integrity. We have previously described that Multivalent Adhesion Molecule (MAM) 7 contributes to initial attachment of V. parahaemolyticus to epithelial cells. Here we show that the bacterial adhesin, through multivalent interactions between surface-induced adhesin clusters and phosphatidic acid lipids in the host cell membrane, induces activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered activation of the ROCK/LIMK signaling axis is sufficient to redistribute tight junction proteins, leading to a loss of epithelial barrier function. Taken together, these findings show an unprecedented mechanism by which an adhesin acts as assembly platform for a host cellular signaling pathway, which ultimately facilitates breaching of the epithelial barrier by a bacterial pathogen. © 2014 Lim et al

The effectiveness and acceptability of multimedia information when recruiting children and young people to trials: the TRECA meta-analysis of SWATs

The information provided to potential trial participants plays a crucial role in their decision-making. Printed participant information sheets for trials have received recurrent criticism as being too long and technical, unappealing and hard to navigate. An alternative is to provide information through multimedia (text, animations, video, audio, diagrams and photos). However, there is limited evidence on the effects of multimedia participant information on research recruitment rates, particularly in children and young people. The study objectives were as follows: 1. to develop template multimedia information resources through participatory design, for use when recruiting children and young people to trials 2. to evaluate the multimedia information resources in a series of Studies Within A Trial, to test their effects on recruitment and retention rates, and participant decision-making, by comparing the provision of multimedia information resources instead of printed participant information sheets, and comparing the provision of multimedia information resources in addition to printed participant information sheets. Two-phase study: 1. multimedia information resources development including qualitative study; user testing study; readability metrics; enhanced patient and public involvement 2. multimedia information resources' evaluation comprising Studies Within A Trial undertaken within host trials recruiting children and young people. United Kingdom trials involving patients aged under 18. Development phase: = 120 (children and young people, parents, clinicians, trial personnel). Evaluation phase: = 1906 (children and young people being asked to take part in trials). Multimedia information resources (comprising text, audio, 'talking heads' video, trial-specific and trial-generic animations). Printed participant information sheets. Primary outcome: trial recruitment rate comparing multimedia information resource-only with printed participant information sheet-only provision. Secondary outcomes: trial recruitment rate comparing combined multimedia information resource and printed participant information sheet with printed participant information sheet-only provision; trial retention rate; quality of participant decision-making. Results for each trial were calculated and combined in a two-stage random-effects meta-analysis. Phase 1 generated two multimedia information resource templates: (1) for children aged 6-11 years; (2) for children aged 12-18 years and parents. In the Phase 2 Studies Within A Trial the multimedia information resources improved trial recruitment, when compared to printed information alone [odds ratio (OR) = 1.54; 95% confidence interval (CI) 1.05 to 2.28; = 0.03; = 0%]. When printed participant information sheet-only provision was compared to combined multimedia information resource and printed participant information sheet provision, there was no effect on trial recruitment (OR = 0.89; 95% CI 0.53 to 1.50; = 0%). There were no differences between multimedia information resource and printed participant information sheet on trial retention or participant decision-making quality. In a study within a hypothetical trial setting, multimedia information resource-only provision produced higher ratings of 'information was easy to understand' ( = 3.03; = 0.003) and 'I had confidence in decision-making' ( = 2.00; = 0.044) than printed participant information sheet-only provision. It was not possible to include data from three Studies Within A Trial in the meta-analysis due to limited sample size, and questionnaire return rates were low, which reduced the strength of the findings. Use of multimedia information increased the rate of recruitment to trials involving children and young people compared to standard patient information sheets. There should be further evaluation of the effects of multimedia information on recruitment to trials involving children and young people. It would be valuable to assess any impacts of multimedia information resources on communication between trial recruiters, children and young people, and parents. This trial is registered as TRECA ISRCTN 73136092 and Northern Ireland Hub for Trials Methodology Research SWAT Repository (SWAT 97). This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 14/21/21) and is published in full in ; Vol. 11, No. 24. See the NIHR Funding and Awards website for further award information

Abstracts from the NIHR INVOLVE Conference 2017

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Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Online Food Nutrition Labelling in the UK: How consistent are supermarkets in their presentation of nutrition labels online?

Objective: To evaluate consistency levels of nutrition labelling on supermarket websites. Design: This is a comparative, quantitative study examining page position, content and design of nutrition labels on own-brand and branded products. Online and in-store nutrition labels were examined, categorised and analysed to discern variety of label designs used and consistency between online and in-store labelling. Setting: Five large online food retailers in the UK. Subjects Nutrition labels displayed on 100 webpages were examined for twenty branded and own-brand products. Equivalent labels on in-store packaged products were also examined. Results: Eight different combinations of nutrition label designs were found. The online supermarket sites were found to use from three to six of these label combinations across the sample. The consistency level between online and in-store package labels ranged from 25 % to 90 %. In many cases the nutrition label required scrolling to view and in all cases items could be purchased without the label being visible from the search result listings. Conclusions: The main recommendation of the paper is that online nutrition labelling needs to be much more consistently presented than is currently practised, both within each website and between online and in-store experiences. Particular attention should be made to polychrome colour and the inclusion of summary graphics. Designers should also ensure visibility of the label and raise its vertical page position. The paper also proposes additional expansion of the use of nutrition information online, using nutrition values as database fields in search criteria and checkout aggregation reporting

Pencil and Pixel: Identifying the relationship between paper-based and computer-based preliminary graphic design processes

This study examines the strengths and weaknesses of using paper-based and computer-based design tools during graphic design ideation. It focuses on student designers' use of these tools, involving both synthesis of form and generation of graphic ideas. The study includes discussions regarding definitions of graphic design, the design process and creativity. It isolates the principles of vertical and lateral thinking as key elements in this process. Key characteristics of sketching and digital designing are examined by theme, referring to both existing empirical research and practitioner testimony. Key themes isolated for discussion include words versus pictures, ambiguity and reinterpretation and the use of ready-made or self-generated forms. It presents results of primary research regarding both design process and outcome. Experiment 1 featured a group of student designers who devised solutions to two graphic design tasks using paper or computer-based tools. Three strategies were examined in detail and it was concluded that paper-based working supports the use ----~~------ .'--------- --.. _-~ .'.-_._._--_._ .. _...._....__._._--_._----_._-----~----------_.__. - - - ... _-_... _-- ---- . -_._--- --------_._-_.. of words and reinterpretation more strongly than digital working. It also demonstrated how the use of ready-mades and use of preinventive forms occurs during digital working, impacting on both fluency of results and efficiency of process. In Experiment 2, students were asked to perform a simple synthesis exercise involving syntactic properties only. A taxonomy of synthesis strategies was developed and this revealed how a potent means of combining form was achieved most often using paper. It was concluded that the act of drawing, and careful logical engagement with form enables more potent results to be made. In terms of originality it was also suggested that paper enabled more unique (in the dataset) solutions to be made than the computer. The study concludes by discussing strategies used when using certain tools in relation to vertical or lateral thinking styles. Both styles are needed in ideation activity. We need to ensure that the educator finds both ways to integrate ideation and tool activity into the curriculum, encouraging the way students use the sketch, and altering the way students use digital tools for ideation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo