Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve

Detection and drivers of exposure and effects of pharmaceuticals in higher vertebrates

Pharmaceuticals are highly bioactive compounds now known to be widespread environmental contaminants. However, research regarding exposure and possible effects in non-target higher vertebrate wildlife remains scarce. The fate and behaviour of most pharmaceuticals entering our environment via numerous pathways remain poorly characterized, and hence our conception and understanding of the risks posed to wild animals is equally constrained. The recent decimation of Asian vulture populations owing to a pharmaceutical (diclofenac) offers a notable example, because the exposure route (livestock carcasses) and the acute toxicity observed were completely unexpected. This case not only highlights the need for further research, but also the wider requirement for more considered and comprehensive ‘ecopharmacovigilance’. We discuss known and potential high risk sources and pathways in terrestrial and freshwater ecosystems where pharmaceutical exposure in higher vertebrate wildlife, principally birds and mammals, may occur. We examine whether approaches taken within existing surveillance schemes (that commonly target established classes of persistent or bioaccumulative contaminants) and the risk assessment approaches currently used for pesticides are relevant to pharmaceuticals, and we highlight where new approaches may be required to assess pharmaceutical-related risk

AMP!: A Cross-site Analysis of the Effects of a Theater-based Intervention on Adolescent Awareness, Attitudes, and Knowledge about HIV

AMP! (Arts-based, Multiple component, Peer-education) is an HIV intervention developed for high school adolescents. AMP! uses interactive theater-based scenarios developed by trained college undergraduates to deliver messages addressing HIV/STI prevention strategies, healthy relationships, and stigma reduction towards people living with HIV/AIDS. We used a pre-test/post-test, control group study design to simultaneously assess intervention effect on ninth grade students in an urban county in California (N = 159) and a suburban county in North Carolina (N = 317). In each location, the control group received standard health education curricula delivered by teachers; the intervention group received AMP! in addition to standard health education curricula. Structural equation modeling was used to determine intervention effects. The post-test sample was 46% male, 90% self-identified as heterosexual, 32% reported receiving free or reduced lunch, and 49% White. Structural models indicated that participation in AMP! predicted higher scores on HIV knowledge (p = .05), HIV awareness (p = .01), and HIV attitudes (p = .05) at the post-test. Latent means comparison analyses revealed post-test scores were significantly higher than pre-test scores on HIV knowledge (p = .001), HIV awareness (p = .001), and HIV attitudes (p = .001). Further analyses indicated that scores rose for both groups, but the post-test scores of intervention participants were significantly higher than controls (HIV knowledge (p = .01), HIV awareness (p = .01), and HIV attitudes (p = .05)). Thus, AMP!’s theater-based approach shows promise for addressing multiple adolescent risk factors and attitudes concerning HIV in school settings

Which providers can bridge the health literacy gap in lifestyle risk factor modification education : a systematic review and narrative synthesis

Background: People with low health literacy may not have the capacity to self-manage their health and prevent the development of chronic disease through lifestyle risk factor modification. The aim of this narrative synthesis is to determine the effectiveness of primary healthcare providers in developing health literacy of patients to make SNAPW (smoking, nutrition, alcohol, physical activity and weight) lifestyle changes. Methods. Studies were identified by searching Medline, Embase, Cochrane Library, CINAHL, Joanna Briggs Institute, Psychinfo, Web of Science, Scopus, APAIS, Australian Medical Index, Community of Science and Google Scholar from 1 January 1985 to 30 April 2009. Health literacy and related concepts are poorly indexed in the databases so a list of text words were developed and tested for use. Hand searches were also conducted of four key journals. Studies published in English and included males and females aged 18 years and over with at least one SNAPW risk factor for the development of a chronic disease. The interventions had to be implemented within primary health care, with an aim to influence the health literacy of patients to make SNAPW lifestyle changes. The studies had to report an outcome measure associated with health literacy (knowledge, skills, attitudes, self efficacy, stages of change, motivation and patient activation) and SNAPW risk factor.The definition of health literacy in terms of functional, communicative and critical health literacy provided the guiding framework for the review. Results: 52 papers were included that described interventions to address health literacy and lifestyle risk factor modification provided by different health professionals. Most of the studies (71%, 37/52) demonstrated an improvement in health literacy, in particular interventions of a moderate to high intensity.Non medical health care providers were effective in improving health literacy. However this was confounded by intensity of intervention. Provider barriers impacted on their relationship with patients. Conclusion: Capacity to provide interventions of sufficient intensity is an important condition for effective health literacy support for lifestyle change. This has implications for workforce development and the organisation of primary health care

Which providers can bridge the health literacy gap in lifestyle risk factor modification education : a systematic review and narrative synthesis

Background: People with low health literacy may not have the capacity to self-manage their health and prevent the development of chronic disease through lifestyle risk factor modification. The aim of this narrative synthesis is to determine the effectiveness of primary healthcare providers in developing health literacy of patients to make SNAPW (smoking, nutrition, alcohol, physical activity and weight) lifestyle changes. Methods. Studies were identified by searching Medline, Embase, Cochrane Library, CINAHL, Joanna Briggs Institute, Psychinfo, Web of Science, Scopus, APAIS, Australian Medical Index, Community of Science and Google Scholar from 1 January 1985 to 30 April 2009. Health literacy and related concepts are poorly indexed in the databases so a list of text words were developed and tested for use. Hand searches were also conducted of four key journals. Studies published in English and included males and females aged 18 years and over with at least one SNAPW risk factor for the development of a chronic disease. The interventions had to be implemented within primary health care, with an aim to influence the health literacy of patients to make SNAPW lifestyle changes. The studies had to report an outcome measure associated with health literacy (knowledge, skills, attitudes, self efficacy, stages of change, motivation and patient activation) and SNAPW risk factor.The definition of health literacy in terms of functional, communicative and critical health literacy provided the guiding framework for the review. Results: 52 papers were included that described interventions to address health literacy and lifestyle risk factor modification provided by different health professionals. Most of the studies (71%, 37/52) demonstrated an improvement in health literacy, in particular interventions of a moderate to high intensity.Non medical health care providers were effective in improving health literacy. However this was confounded by intensity of intervention. Provider barriers impacted on their relationship with patients. Conclusion: Capacity to provide interventions of sufficient intensity is an important condition for effective health literacy support for lifestyle change. This has implications for workforce development and the organisation of primary health care

Implementing a 48 h EWTD-compliant rota for junior doctors in the UK does not compromise patients’ safety : assessor-blind pilot comparison

Background: There are currently no field data about the effect of implementing European Working Time Directive (EWTD)-compliant rotas in a medical setting. Surveys of doctors’ subjective opinions on shift work have not provided reliable objective data with which to evaluate its efficacy. Aim: We therefore studied the effects on patient's safety and doctors’ work-sleep patterns of implementing an EWTD-compliant 48 h work week in a single-blind intervention study carried out over a 12-week period at the University Hospitals Coventry & Warwickshire NHS Trust. We hypothesized that medical error rates would be reduced following the new rota. Methods: Nineteen junior doctors, nine studied while working an intervention schedule of <48 h per week and 10 studied while working traditional weeks of <56 h scheduled hours in medical wards. Work hours and sleep duration were recorded daily. Rate of medical errors (per 1000 patient-days), identified using an established active surveillance methodology, were compared for the Intervention and Traditional wards. Two senior physicians blinded to rota independently rated all suspected errors. Results: Average scheduled work hours were significantly lower on the intervention schedule [43.2 (SD 7.7) (range 26.0–60.0) vs. 52.4 (11.2) (30.0–77.0) h/week; P < 0.001], and there was a non-significant trend for increased total sleep time per day [7.26 (0.36) vs. 6.75 (0.40) h; P = 0.095]. During a total of 4782 patient-days involving 481 admissions, 32.7% fewer total medical errors occurred during the intervention than during the traditional rota (27.6 vs. 41.0 per 1000 patient-days, P = 0.006), including 82.6% fewer intercepted potential adverse events (1.2 vs. 6.9 per 1000 patient-days, P = 0.002) and 31.4% fewer non-intercepted potential adverse events (16.6 vs. 24.2 per 1000 patient-days, P = 0.067). Doctors reported worse educational opportunities on the intervention rota. Conclusions: Whilst concerns remain regarding reduced educational opportunities, our study supports the hypothesis that a 48 h work week coupled with targeted efforts to improve sleep hygiene improves patient safety

Global Reprogramming of Host SUMOylation during Influenza Virus Infection

Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here,we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome re-modeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection