Evaluating the effectiveness of a schools-based programme to promote exercise self-efficacy in children and young people with risk factors for obesity: Steps to active kids (STAK)

<p>Abstract</p> <p>Background</p> <p>Low levels of physical activity in children have been linked to an increased risk of obesity, but many children lack confidence in relation to exercise (exercise self-efficacy). Factors which can impact on confidence include a chronic health condition such as asthma, poor motor skills and being overweight. Increasing levels of physical activity have obvious benefits for children with asthma and children who are overweight, but few activity interventions with children specifically target children with low exercise self-efficacy (ESE). This study aims to evaluate the efficacy and feasibility of a schools-based activity programme suitable for children with risk factors for adult obesity, including asthma, overweight and low exercise self-efficacy.</p> <p>Methods/Design</p> <p>A clustered (at the level of school) RCT will be used to compare a targeted, 10 week, stepped activity programme (activity diary, dance DVD, circuit-training and motivational interviewing) designed to promote ESE. We will recruit 20 primary schools to participate in the intervention and 9-11 year old children will be screened for low levels of ESE, asthma and overweight. In order to provide sufficient power to detect a difference in primary outcomes (Body Mass Index-BMI & ESE at 12 month follow-up) between children in the intervention schools and control schools, the target sample size is 396. Assessments of BMI, ESE, waist circumference, peak flow, activity levels and emotional and behavioural difficulties will be made at baseline, 4 months and 12 month follow-up.</p> <p>Discussion</p> <p>We aim to increase ESE and levels of physical activity in children with risk factors for adult obesity. The outcomes of this study will inform policy makers about the feasibility, acceptability and effectiveness of delivering targeted health interventions within a school setting.</p> <p>Trial Registration</p> <p>ISRCTN Register no. <a href="http://www.controlled-trials.com/ISRCTN12650001">ISRCTN12650001</a></p

Preclinical mouse models for BRCA1-associated breast cancer

A substantial part of all hereditary breast cancer cases is caused by BRCA1 germline mutations. In this review, we will discuss the insights into BRCA1 functions that we obtained from mouse models with conventional and conditional mutations in Brca1. The most advanced models closely resemble human BRCA1-related breast cancer and may therefore be useful for addressing clinically relevant questions

The Princess Marina Hospital accident and emergency triage scale provides highly reliable triage acuity ratings

Geneeskunde en GesondheidswetenskappeNoodgeneeskundePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Visualization and quantification of APP intracellular domain-mediated nuclear signaling by bimolecular fluorescence complementation

BACKGROUND: The amyloid precursor protein (APP) intracellular domain (AICD) is released from full-length APP upon sequential cleavage by either α- or β-secretase followed by γ-secretase. Together with the adaptor protein Fe65 and the histone acetyltransferase Tip60, AICD forms nuclear multiprotein complexes (AFT complexes) that function in transcriptional regulation. OBJECTIVE: To develop a medium-throughput machine-based assay for visualization and quantification of AFT complex formation in cultured cells. METHODS: We used cotransfection of bimolecular fluorescence complementation (BiFC) fusion constructs of APP and Tip60 for analysis of subcellular localization by confocal microscopy and quantification by flow cytometry (FC). RESULTS: Our novel BiFC-constructs show a nuclear localization of AFT complexes that is identical to conventional fluorescence-tagged constructs. Production of the BiFC signal is dependent on the adaptor protein Fe65 resulting in fluorescence complementation only after Fe65-mediated nuclear translocation of AICD and interaction with Tip60. We applied the AFT-BiFC system to show that the Swedish APP familial Alzheimer's disease mutation increases AFT complex formation, consistent with the notion that AICD mediated nuclear signaling mainly occurs following APP processing through the amyloidogenic β-secretase pathway. Next, we studied the impact of posttranslational modifications of AICD on AFT complex formation. Mutation of tyrosine 682 in the YENPTY motif of AICD to phenylalanine prevents phosphorylation resulting in increased nuclear AFT-BiFC signals. This is consistent with the negative impact of tyrosine phosphorylation on Fe65 binding to AICD. Finally, we studied the effect of oxidative stress. Our data shows that oxidative stress, at a level that also causes cell death, leads to a reduction in AFT-BiFC signals. CONCLUSION: We established a new method for visualization and FC quantification of the interaction between AICD, Fe65 and Tip60 in the nucleus based on BiFC. It enables flow cytometric analysis of AICD nuclear signaling and is characterized by scalability and low background fluorescence

Intravenous Fluid Bolus Rates Associated with Outcomes in Pediatric Sepsis: A Multi-Center Analysis

Paul C Mullan,1 Christopher M Pruitt,2 Kelly A Levasseur,3 Charles G Macias,4 Raina Paul,5 Holly Depinet,6 Anh Thy H Nguyen,7 Elliot Melendez8 1Department of Pediatrics, Division of Emergency Medicine, Eastern Virginia Medical School, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA; 2Department of Pediatrics, Division of Pediatric Emergency Medicine, Medical University of South Carolina, Charleston, SC, USA; 3Pediatric Emergency Medicine, Beaumont Children’s Hospital, Royal Oak, MI, USA; 4Division of Pediatric Emergency Medicine, University Hospitals Rainbow Babies and Children’s, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 5Department of Emergency Medicine, Advocate Children’s Hospital, Park Ridge, IL, USA; 6Division of Emergency Medicine, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH, USA; 7Johns Hopkins All Children’s Institute for Clinical and Translational Research, St. Petersburg, FL, USA; 8Division of Pediatric Critical Care, Connecticut Children’s Medical Center, University of Connecticut, Hartford, CT, USACorrespondence: Paul C Mullan, Email [email protected]: Pediatric sepsis guidelines recommend rapid intravenous fluid (IVF) bolus administration rates (BAR). Recent sepsis studies suggest that rapid BAR may be associated with increased morbidity. We aimed to describe the association between emergency department (ED) IVF BAR and clinical outcomes in pediatric sepsis.Patients and Methods: Secondary post-hoc analysis of retrospective cohort data from 19 hospitals in the Pediatric Septic Shock Collaborative (PSSC) database. Patients with presumed septic shock were defined by severe sepsis/septic shock diagnostic codes, receipt of septic shock therapies, or floor-to-ICU transfers within 12 hours from ED admission for septic shock. Patients (2 months– 21 years) with complete data on weight, antibiotic receipt, bolus timing, and bolus volumes were included. The primary outcome was 30-day mortality. Associations between BAR and mortality and secondary (intubation or non-invasive positive pressure ventilation = NIPPV) outcomes were assessed using unadjusted and adjusted logistic regression.Results: The PSSC database included 6731 patients; 3969 met inclusion and received a median ED volume of 40.2 mL/kg. Seventy-six (1.9%) patients died, 151 (3.8%) were intubated, and 235 (5.9%) had NIPPV administered. The median BAR was 25.7 mL/kg/hr. For each 20 mL/kg/hr increase in BAR, the adjusted odds ratio (aOR) for 30-day mortality [aOR = 1.11 (95% CI 1.01, 1.23)], intubation [aOR = 1.25 (95% CI 1.09, 1.44)], and NIPPV [aOR = 1.20 (95% CI 1.05, 1.38)] significantly increased.Conclusion: Faster ED IVF bolus administration rates in this pediatric sepsis database were associated with higher adjusted odds of death, intubation and NIPPV. Controlled trials are needed to determine if these associations are replicable.Keywords: emergency department, mortality, intubation, collaborativ