Adenovirus E4orf4 Induces HPV-16 Late L1 mRNA Production

The adenovirus E4orf4 protein regulates the switch from early to late gene expression during the adenoviral replication cycle. Here we report that overexpression of adenovirus E4orf4 induces human papillomavirus type 16 (HPV-16) late gene expression from subgenomic expression plasmids. E4orf4 specifically overcomes the negative effects of two splicing silencers at the two late HPV-16 splice sites SD3632 and SA5639. This results in the production of HPV-16 spliced L1 mRNAs. We show that the interaction of E4orf4 with protein phosphatase 2A (PP2A) is necessary for induction of HPV-16 late gene expression. Also an E4orf4 mutant that fails to bind the cellular splicing factor ASF/SF2 fails to induce L1 mRNA production. Collectively, these results suggest that dephosphorylation of SR proteins by E4orf4 activates HPV-16 late gene expression. Indeed, a mutant ASF/SF2 protein in which the RS-domain had been deleted could itself induce HPV-16 late gene expression, whereas wild type ASF/SF2 could not

Project Energize: Intervention development and 10 years of progress in preventing childhood obesity Public Health

Prevention of childhood obesity is a global priority. The school setting offers access to large numbers of children and the ability to provide supportive environments for quality physical activity and nutrition. This article describes Project Energize, a through-school physical activity and nutrition programme that celebrated its 10-year anniversary in 2015 so that it might serve as a model for similar practices, initiatives and policies elsewhere. The programme was envisaged and financed by the Waikato District Health Board of New Zealand in 2004 and delivered by Sport Waikato to 124 primary schools as a randomised controlled trial from 2005 to 2006. The programme has since expanded to include all 242 primary schools in the Waikato region and 70 schools in other regions, including 53,000 children. Ongoing evaluation and development of Project Energize has shown it to be sustainable (ongoing for \u3e10 years), both effective (lower obesity, higher physical fitness) and cost effective (one health related cost quality adjusted life year between $18,000 and$30,000) and efficient ($45/child/year) as a childhood \u27health\u27 programme. The programme\u27s unique community-based approach is inclusive of all children, serving a population that is 42 % Ma¯ori, the indigenous people of New Zealand. While the original nine healthy eating and seven quality physical activity goals have not changed, the delivery and assessment processes has been refined and the health service adapted over the 10 years of the programme existence, as well as adapted over time to other settings including early childhood education and schools in Cork in Ireland. Evaluation and research associated with the programme delivery and outcomes are ongoing. The dissemination of findings to politicians and collaboration with other service providers are both regarded as priorities

Final Report for The Lydia Osteoporosis Project

Sharing Research and Education Focused on Moving and Handling and Older People with Osteoporosis in Acute Settingssch_nurAge UK www.ageuk.org.uk accessed 30th June 2016 Biggs J and Tang C 2011 Teaching for Quality Learning at University (Society for Research into Higher Education) SRHE and Open University Press Imprint, Maidenhead, UK. Blaikie, N. 2009 Designing Social Research. Polity Press, Cambridge, UK. Colon-Emeric, CS., Lyles, KW., House, P., Levine, DA., Schenck, AP., et al. 2007 Randomised trial to improve fracture prevention in nursing home residents American Journal of Medicine 120 (10) 886 -892 Coulter Smith M A, O'May F, Tropea S, Berg J 2016 Framing moving and handling as a complex intervention in the acute care of older adults with osteoporosis: A qualitative study. Journal of Clinical Nursing. Accepted for publication 19th April 2016. Wiley Open Access. Unique ID: 5511802- 1606658. Cox, H., Puffer, S., Morton, V. et al. 2008 Educating nursing home staff on fracture prevention: a cluster randomised trial Age and Ageing 37 167-172 Foss, NB., Pal, H., Kehlet, H. 2005 In hospital hip fractures: prevalence, risk factors, and outcome. Research Letter. Age Ageing 34, (6) 642-645. Doi:10.1093/ ageing/alfi198 Giangregorio, L., Fisher, P., Papaioannou, A., Adachi, JD. 2007 Osteoporosis knowledge and information needs in healthcare professionals caring for patients with fragility fractures Orthopaedic Nursing 26 (1) 27 - 35 Haentjens P, Magaziner J, Col_n-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B, Boonen S 2010 Meta-analysis: Excess Mortality After Hip Fracture Among Older Women and Men. Ann. Intern. Med. 152, (6), 380-390. doi: 10.7326/0003-4819-152-6-201003160- 00008. Harvey, G., & Kitson, A. 2015 Implementing Evidence Based Practice in Healthcare. A Facilitation Guide. Routledge, London. Hignett, S. 2003 Systematic review of patient handling activities starting in lying, sitting and standing positions. Journal Advanced Nursing 41 (6) 545-552 Hignett, S., Crumpton, E., Ruszola S. et al. 2004 Evidence-Based Patient Handling. Tasks, Equipment and Interventions Routledge, London Hippisley-Cox, J., Coupland, C. 2012 Derivation and validation of updated QFracture algorithm to predict risk of osteoporotic fracture in primary care in the United Kingdom: prospective open cohort study. BMJ. 344, e3427. doi: 10.1136/bmj.e3427. International Osteoporosis Foundation (IOF) 2015 http://www.iofbonehealth.org/factsstatistics Accessed 21st December 2015 International Osteoporosis Foundation 2010 The Breaking Spine http://www.iofbonehealth.org/ publications/the-breaking-spine.html Accessed 2nd March 2011 Jonassen, D., & Land, S. 2012 Theoretical Foundations of Learning Environments 2nd edition Oxon, Routledge Joop, PW., van den Bergh., Tineke ACM van Geel., Willem, FL., et al. 2010 Assessment of Individual Fracture Risk: FRAX and Beyond Current Osteoporosis Reports 8 131-137 Kanis, JA., McCloskey, EV., Johansson, H., Cooper, C., Rizzoli , R., Reginster, JY. 2013 European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 24, 23-57 doi 10.1007/ s00198-012-2074-y Kanis, JA. , Johnell, O., Oden, A. et al. 2008 European guidance for the diagnosis and management of osteoporosis in postmenopausal women Osteoporosis International 19 399-428 Kanis, JA. 2007 on behalf of World Health Organization Scientific Group. Assessment of osteoporosis at the primary health care level. Technical report. UK: World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield; 2007. Available from https://www.shef.ac.uk/ FRAX/pdfs/WHO_Technical_Report.pdf Accessed 6th December 2015 Kanis, JA, Borgstrom, F., De Laet, C., et al. 2005 Assessment of fracture risk Osteoporosis International 16 581-589 Kneafsey, R., Clifford, C., Greenfield, S. 2013 What is the nursing team involvement in maintaining and promoting the mobility of older adults in hospital? A grounded theory study International Journal of Nursing Studies 50 1617-1629 http://dx.doi.org/10.1016/j. ijnurstu.2013.04.007 Kneafsey, R., & Haigh, C. 2009 Moving and handling rehabilitation patients: A survey of nurses' views International Journal of Therapy & Rehabilitation 16 (8) 431- 440 McCormack, B. 2015 Action research in complex interventions Chpt. 31. In Richards D A., & Rahm Hallberg I. Eds. 2015 Complex Interventions In Health. An Overview of Research Methods. Routledge, London McLellan, AR., Reid, DM., Forbes, K., et al. 2004 Effectiveness of Strategies for the Secondary Prevention of Osteoporotic Fractures in Scotland Executive Summary CEPS: 99/03 NHS Quality Improvement Scotland Mezirow, J. 2009 An overview on transformative learning. In: Illeris, K. ed. Contemporary Theories of Learning. Oxon: Routledge. p. 90 Moon, JA. 2004 A Handbook of Reflective and Experiential Learning. Theory and Practice London, New York: Routledge Moorchilot, R., Masud, T. 2010 The role of fracture prediction in managing osteoporosis Geriatric Medicine 40 (12) 671-2, 674-5 Mortiboys, A. 2012. Teaching with Emotional Intelligence: A Step-by-step Guide for Higher and Further Education Professionals. Oxon: Routledge National Osteoporosis Society (NOS) 2015 http://www.nos.org.uk accessed 29th June 2016 National Osteoporosis Guidelines Group (NOGG 2000) http://www.shef.ac.uk/NOGG/ accessed 2nd November 2010 NICE 2008 Osteoporosis: Assessment of fracture risk and the prevention of osteoporotic fractures in individuals at high risk National collaborating centre for nursing and supportive care Osteoporosis Evidence Review NICE accessed March 2011 NICE 2004 Technologies for the prevention and treatment of osteoporosis and prevention of osteoporotic fractures in postmenopausal women http://www.nice.org.uk/guidance/index. jsp?action=article&r=true&o=32980 accessed March 2011 QMU 2011 QMU Research Code of Practice. Queen Margaret University, Edinburgh Reason, P., Bradbury, H. 2006 Eds. Handbook of Action Research. Sage. London Rizzoli, R., Branco, J., Brandi, M.L., Boonen, S., Bruyre, O., Cacoub, P., Cooper, C., Diez-Perez, A., Duder, J., Fielding, R.A., Harvey, N.C., Hiligsmann, M., Kanis, J.A., Petermans, J., Ringe, J.D., Tsouderos. Y., Weinman, J., Reginster, J.Y. 2014. Management of osteoporosis in the oldest old. Osteoporosis Int. 25 (11), 2507-2529. SIGN 2015 Scottish Intercollegiate Guideline Network Management of Osteoporosis. SIGN 142. Management of osteoporosis and the prevention of fragility fractures. A national clinical guideline RCP, Edinburgh Smith, J. (Ed) 2005 The Guide to the Handling of People. 5thEdition. Backcare in collaboration with RCN & National Back Exchange, Teddington Taylor, J., Hill, H., Kay, K. 2016 NS835. An integrated practice approach to mobility care for older people. Nursing Standard. 30 (29) 51-59 Tashakkori, A., & Teddlie, C. 1998 Mixed Methodology. Combining Qualitative and Quantitative Approaches. Applied Social Research Methods Series. Volume 46. Sage Publications, London Teddlie, C., & Tashakkori, A. 2009 Foundations of Mixed Methods Research. Integrating Quantitative and Qualitative Approaches in the Social and Behavioral Sciences. Sage, London. Van Merrinboer, J.J.G., & Kirschner P. A. 2013 Ten Steps to Complex Learning. A Systematic Approach to Four-component Instructional Design. 2nd ed. Routledge, London. Vered, I., Werner, P., Shemy, G., Stone, O. 2008 Nurses' knowledge and perceptions about osteoporosis: a questionnaire survey. International Journal of Nursing Studies 45 (6) 847 - 854 WHO 2008 FRAX tool http://www.shef.ac.uk/ FRAX/ accessed 30th June 2016pub4419pu

Le FORUM, Vol. 37 No. 1

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Le FORUM, Vol. 36 No. 3

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Predictors of segmental myocardial functional recovery in patients after an acute ST-elevation myocardial infarction

Objective: We hypothesized that Displacement Encoding with Stimulated Echoes (DENSE) and feature-tracking derived circumferential strain would provide incremental prognostic value over the extent of infarction for recovery of segmental myocardial function. Methods: Two hundred and sixty-one patients (mean age 59 years, 73% male) underwent MRI 2 days post-ST elevation myocardial infarction (STEMI) and 241 (92%) underwent repeat imaging 6 months later. The MRI protocol included cine, 2D-cine DENSE, T2 mapping and late enhancement. Wall motion scoring was assessed by 2-blinded observers and adjudicated by a third. (WMS: 1=normal, 2=hypokinetic, 3=akinetic, 4=dyskinetic). WMS improvement was defined as a decrease in WMS ≥ 1, and normalization where WMS = 1 on follow-up. Segmental circumferential strain was derived utilizing DENSE and feature-tracking. A generalized linear mixed model with random effect of subject was constructed and used to account for repeated sampling when investigating predictors of segmental myocardial improvement or normalization Results: At baseline and follow-up, 1416 segments had evaluable data for all parameters. Circumferential strain by DENSE (p < 0.001) and feature-tracking (p < 0.001), extent of oedema (p < 0.001), infarct size (p < 0.001), and microvascular obstruction (p < 0.001) were associates of both improvement and normalization of WMS. Circumferential strain provided incremental predictive value even after accounting for infarct size, extent of oedema and microvascular obstruction, for segmental improvement (DENSE: odds ratio, 95% confidence intervals: 1.08 per −1% peak strain, 1.05–1.12, p < 0.001, feature-tracking: odds ratio, 95% confidence intervals: 1.05 per −1% peak strain, 1.03–1.07, p < 0.001) and segmental normalization (DENSE: 1.08 per −1% peak strain, 1.04–1.12, p < 0.001, feature-tracking: 1.06 per −1% peak strain, 1.04–1.08, p < 0.001). Conclusions: Circumferential strain provides incremental prognostic value over segmental infarct size in patients post STEMI for predicting segmental improvement or normalization by wall-motion scoring

1-year outcomes of angina management guided by invasive coronary function testing (CorMicA)

Objectives: The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery disease. Background: Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease. Methods: A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure–facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life [EQ-5D]) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up. Results: Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p < 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units [18%]; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803). Conclusions: Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina [CorMicA]; NCT03193294