Coagulation and coagulation signalling in fibrosis

AbstractFollowing tissue injury, a complex and coordinated wound healing response comprising coagulation, inflammation, fibroproliferation and tissue remodelling has evolved to nullify the impact of the original insult and reinstate the normal physiological function of the affected organ. Tissue fibrosis is thought to result from a dysregulated wound healing response as a result of continual local injury or impaired control mechanisms. Although the initial insult is highly variable for different organs, in most cases, uncontrolled or sustained activation of mesenchymal cells into highly synthetic myofibroblasts leads to the excessive deposition of extracellular matrix proteins and eventually loss of tissue function. Coagulation was originally thought to be an acute and transient response to tissue injury, responsible primarily for promoting haemostasis by initiating the formation of fibrin plugs to enmesh activated platelets within the walls of damaged blood vessels. However, the last 20years has seen a major re-evaluation of the role of the coagulation cascade following tissue injury and there is now mounting evidence that coagulation plays a critical role in orchestrating subsequent inflammatory and fibroproliferative responses during normal wound healing, as well as in a range of pathological contexts across all major organ systems. This review summarises our current understanding of the role of coagulation and coagulation initiated signalling in the response to tissue injury, as well as the contribution of uncontrolled coagulation to fibrosis of the lung, liver, kidney and heart. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease

Models in dissemination and implementation research: useful tools in public health services and systems research

Dissemination and implementation (D&I) science seeks to understand how to systematically facilitate utilization of evidence. Theories and frameworks (hereafter called models) augment D&I research by enhancing efforts to spread evidence-based interventions (EBIs). D&I models are relevant for public health services and systems research, which also explores the uses of evidence. This report: 1) develops an inventory of models; 2) synthesizes this information; and 3) provides guidance on how to select a model. The research team used snowball sampling to collect models. This article uses three author-defined variables: construct flexibility, focus on dissemination and/or implementation activities, and socio-ecological framework level to categorize models. Models that addressed policy are noted. Public health researchers and practitioners can use this inventory to identify models to guide D&I research and/or efforts

Dissemination and implementation science training needs: Insights from practitioners and researchers

INTRODUCTION: Dissemination and implementation research training has great potential to improve the impact and reach of health-related research; however, research training needs from the end user perspective are unknown. This paper identifies and prioritizes dissemination and implementation research training needs. METHODS: A diverse sample of researchers, practitioners, and policymakers was invited to participate in Concept Mapping in 2014–2015. Phase 1 (Brainstorming) gathered participants' responses to the prompt: To improve the impact of research evidence in practice and policy settings, a skill in which researchers need more training is… The resulting statement list was edited and included subsequent phases. Phase 2 (Sorting) asked participants to sort each statement into conceptual piles. In Phase 3 (Rating), participants rated the difficulty and importance of incorporating each statement into a training curriculum. A multidisciplinary team synthesized and interpreted the results in 2015–2016. RESULTS: During Brainstorming, 60 researchers and 60 practitioners/policymakers contributed 274 unique statements. Twenty-nine researchers and 16 practitioners completed sorting and rating. Nine concept clusters were identified: Communicating Research Findings, Improve Practice Partnerships, Make Research More Relevant, Strengthen Communication Skills, Develop Research Methods and Measures, Consider and Enhance Fit, Build Capacity for Research, and Understand Multilevel Context. Though researchers and practitioners had high agreement about importance (r =0.93) and difficulty (r =0.80), ratings differed for several clusters (e.g., Build Capacity for Research). CONCLUSIONS: Including researcher and practitioner perspectives in competency development for dissemination and implementation research identifies skills and capacities needed to conduct and communicate contextualized, meaningful, and relevant research

Parent–child interactions during pediatric venipuncture: Investigating the role of parent traits, beliefs, and behaviors in relation to child outcomes

Background: The social context is critical to children’s pain, and parents frequently form a major aspect of this context. We addressed several gaps in our understanding of parent–child interactions during painful procedures and identified intrapersonal contributions to parental affective responses and behaviors. We used the pain empathy model framework to examine parent–child interactions during venipuncture to determine predictors of parent distraction and reassurance. Aims: We examined relations among parent and child behaviors along with parent fear and child pain and fear. We empirically tested the contribution of top-down influences in predicting the use of two common parent utterances, reassurance and distraction during venipuncture, including parent beliefs about these behaviors. Methods: Venipunctures of 100 5- to 10-year-old children were filmed, and parent–child interactions were coded using the full 35 item Child Adult Medical Procedure Interaction Scale. Two codes were of particular interest: reassurance and distraction. Self-report measures included child fear and pain, parent fear, trait anxiety, empathy, pain catastrophizing, and beliefs about reassurance and distraction. Results: Findings supported original Child–Adult Medical Procedure Interaction Scale codes linking parent “distress-promoting” behaviors with poorer child outcomes and parent “coping-promoting” behaviors with improved child outcomes. Parent traits accounted for a small portion of the variance in parent reassurance and distraction. Conclusions: Findings are consistent with research on coping and distress promoting behaviors. Using a novel framework of the pain empathy model, we found that parent traits largely did not predict their procedural behaviors, which were more strongly related to child distress behaviors during the needle and parent beliefs about the behaviors

Causal claims about correlations reduced in press releases following academic study of health news

Background: Exaggerations in health news were previously found to strongly associate with similar exaggerations in press releases. Moreover such exaggerations did not appear to attract more news. Here we assess whether press release practice changed after these reported findings; simply drawing attention to the issue may be insufficient for practical change, given the challenges of media environments. Methods: We assessed whether rates of causal over-statement in press releases based on correlational data were lower following a seminal paper on the topic, compared to an equivalent baseline period in the preceding year. Results: We found that over-statements in press releases reduced from 28% (95% confidence interval = 16% to 45%) in 2014 to 13% (95% confidence interval = 6% to 25%) in 2015. A corresponding numerical reduction in exaggerations in news was not significant. The association between over-statements in news and press releases remained strong. Conclusions: Press release over-statements were less frequent following publication of Sumner et al. (2014), indicating that press release practice is malleable. However, this is correlational evidence and the reduction may be due to other factors

Mechanistic overlap between chronic lung injury and cancer:ERS Lung Science Conference 2017 report

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Do restrained eaters show increased BMI, food craving and disinhibited eating? A comparison of the Restraint Scale and the Restrained Eating scale of the Dutch Eating Behaviour Questionnaire

Despite being used interchangeably, different measures of restrained eating have been associated with different dietary behaviours. These differences have impeded replicability across the restraint literature and have made it difficult for researchers to interpret results and use the most appropriate measure for their research. Across a total sample of 1731 participants, this study compared the Restraint Scale (RS), and its subscales, to the Dutch Eating Behaviour Questionnaire (DEBQ) across several traits related to overeating. The aim was to explore potential differences between these two questionnaires so that we could help to identify the most suitable measure as a prescreening tool for eating-related interventions. Results revealed that although the two measures are highly correlated with one another (rs = 0.73–0.79), the RS was more strongly associated with external (rs = −0.07 to 0.11 versus −0.18 to −0.01) and disinhibited eating (rs = 0.46 versus 0.31), food craving (rs = 0.12–0.27 versus 0.02–0.13 and 0.22 versus −0.06) and body mass index (rs = 0.25–0.34 versus −0.13 to 0.15). The results suggest that, compared to the DEBQ, the RS is a more appropriate measure for identifying individuals who struggle the most to control their food intake

TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells

The major high-affinity thrombin receptor, proteinase activated receptor-1 (PAR-1) is expressed at low levels by the normal epithelium but is upregulated in many types of cancer, including lung cancer. The thrombin-PAR-1 signalling axis contributes to the activation of latent TGFβ in response to tissue injury via an avβ6 integrin-mediated mechanism. TGFβ is a pleiotropic cytokine that acts as a tumour suppressor in normal and dysplastic cells but switches into a tumour promoter in advanced tumours. In this study we demonstrate that TGFβ is a positive regulator of PAR-1 expression in A549 lung adenocarcinoma cells, which in turn increases the sensitivity of these cells to thrombin signalling. We further demonstrate that this effect is Smad3-, ERK1/2-and Sp1-dependent. We also show that TGFβ-mediated PAR-1 upregulation is accompanied by increased expression of integrin av and β6 subunits. Finally, TGFβ pre-stimulation promotes increased migratory potential of A549 to thrombin. These data have important implications for our understanding of the interplay between coagulation and TGFβ signalling responses in lung cancer