An Elisa-Based Platform for Rapid Identification of Structure-Dependent Nucleic Acid-Protein Interactions Detects Novel DNA Triplex Interactors

Unusual nucleic acid structures play vital roles as intermediates in many cellular processes and, in the case of peptide nucleic acid (PNA)-mediated triplexes, are leveraged as tools for therapeutic gene editing. However, due to their transient nature, an understanding of the factors that interact with and process dynamic nucleic acid structures remains limited. Here, we developed snapELISA (structure-specific nucleic acid-binding protein ELISA), a rapid high-throughput platform to interrogate and compare up to 2688 parallel nucleic acid structure-protein interactions in vitro. We applied this system to both triplex-forming oligonucleotide-induced DNA triplexes and DNA-bound PNA heterotriplexes to describe the identification of previously known and novel interactors for both structures. For PNA heterotriplex recognition analyses, snapELISA identified factors implicated in nucleotide excision repair (XPA, XPC), single-strand annealing repair (RAD52), and recombination intermediate structure binding (TOP3A, BLM, MUS81). We went on to validate selected factor localization to genome-targeted PNA structures within clinically relevant loci in human cells. Surprisingly, these results demonstrated XRCC5 localization to PNA triplex-forming sites in the genome, suggesting the presence of a double-strand break intermediate. These results describe a powerful comparative approach for identifying structure-specific nucleic acid interactions and expand our understanding of the mechanisms of triplex structure recognition and repair

Scaling up community-based obesity prevention in Australia: Background and evaluation design of the Health Promoting Communities: Being Active Eating Well initiative

Background : There is only limited evidence available on how best to prevent childhood obesity and community-based interventions hold promise, as several successful interventions have now been published. The Victorian Government has recently funded six disadvantaged communities across Victoria, Australia for three years to promote healthy eating and physical activity for children, families, and adults in a community-based participatory manner. Five of these intervention communities are situated in Primary Care Partnerships and are the subject of this paper. The interventions will comprise a mixture of capacity-building, environmental, and whole-of-community approaches with targeted and population-level interventions. The specific intervention activities will be determined locally within each community through stakeholder and community consultation. Implementation of the interventions will occur through funded positions in primary care and local government. This paper describes the design of the evaluation of the five primary care partnership-based initiatives in the \u27Go for your life\u27 Health Promoting Communities: Being Active Eating Well (HPC:BAEW) initiative.Methods/Design : A mixed method and multi-level evaluation of the HPC:BAEW initiative will capture process, impact and outcome data and involve both local and state-wide evaluators. There will be a combined analysis across the five community intervention projects with outcomes compared to a comparison group using a cross-sectional, quasi-experimental design. The evaluation will capture process, weight status, socio-demographic, obesity-related behavioral and environmental data in intervention and comparison areas. This will be achieved using document analysis, paper-based questionnaires, interviews and direct measures of weight, height and waist circumference from participants (children, adolescents and adults).Discussion : This study will add significant evidence on how to prevent obesity at a population level in disadvantaged and ethnically diverse communities. The outcomes will have direct influence on policy and practice and guide the development and implementation of future obesity prevention efforts in Australia and internationally.<br /

Reducing unhealthy weight gain in children through community capacity−building: results of a quasi−experimental intervention program, Be Active Eat Well

Background:Be Active Eat Well (BAEW) was a multifaceted community capacity-building program promoting healthy eating and physical activity for children (aged 4&ndash;12 years) in the Australian town of Colac.Objective:To evaluate the effects of BAEW on reducing children\u27s unhealthy weight gain.Methods:BAEW had a quasi-experimental, longitudinal design with anthropometric and demographic data collected on Colac children in four preschools and six primary schools at baseline (2003, n=1001, response rate: 58%) and follow-up (2006, n=839, follow-up rate: 84%). The comparison sample was a stratified random selection of preschools (n=4) and primary schools (n=12) from the rest of the Barwon South Western region of Victoria, with baseline assessment in 2003&ndash;2004 (n=1183, response rate: 44%) and follow-up in 2006 (n=979, follow-up rate: 83%).Results:Colac children had significantly lower increases in body weight (mean: -0.92 kg, 95% CI: -1.74 to -0.11), waist (-3.14 cm, -5.07 to -1.22), waist/height (-0.02, -0.03 to -0.004), and body mass index z-score (-0.11, -0.21 to -0.01) than comparison children, adjusted for baseline variable, age, height, gender, duration between measurements and clustering by school. In Colac, the anthropometric changes were not related to four indicators of socioeconomic status (SES), whereas in the comparison group 19/20 such analyses showed significantly greater gains in anthropometry in children from lower SES families. Changes in underweight and attempted weight loss were no different between the groups.Conclusions:Building community capacity to promote healthy eating and physical activity appears to be a safe and effective way to reduce unhealthy weight gain in children without increasing health inequalities.<br /

Integrated Short-term Palliative Rehabilitation to improve quality of life and equitable care access in incurable cancer (INSPIRE): a multinational European research project

Background: Disability related to incurable cancer affects over a million Europeans each year and people with cancer rank loss of function among the most common unmet supportive care needs. Objectives: To test the clinical and cost-effectiveness of an integrated short-term palliative rehabilitation intervention, to optimise function and quality of life in people affected by incurable cancer. Design: This is a multinational, parallel group, randomised, controlled, assessor blind, superiority trial. Methods: The INSPIRE consortium brings together leaders in palliative care, oncology and rehabilitation from partner organisations across Europe, with complementary expertise in health service research, trials of complex interventions, mixed-method evaluations, statistics and economics. Partnership with leading European civil society organisations ensures citizen engagement and dissemination at the highest level. We will conduct a multinational randomised controlled trial across five European countries, recruiting participants to assess the effectiveness of palliative rehabilitation for people with incurable cancer on the primary outcome – quality of life – and secondary outcomes including disability, symptom burden and goal attainment. To support trial conduct and enhance analysis of trial data, we will also conduct: comparative analysis of current integration of rehabilitation across oncology and palliative care services; mixed-method evaluations of equity and inclusivity, processes and implementation for the intervention, at patient, health service and health system levels. Finally, we will conduct an evidence synthesis, incorporating INSPIRE findings, and a Delphi consensus to develop an international framework for palliative rehabilitation practice and policy, incorporating indicators, core interventions, outcomes and integration methods. Scientific contribution: If positive, the trial could produce a scalable and equitable intervention to improve function and quality of life in people with incurable cancer and reduce the burden of care for their families. It could also upskill the practitioners involved and motivate future research questions. The intervention could be adapted and integrated into different health systems using existing staff and services, with little or no additional cost

A pilot and feasibility study to assess children’s consumption in quick-service restaurants using plate waste methodology

Background: Children regularly consume foods from quick-service restaurants (QSR), but little is known about the foods that children order, the calories and nutrients consumed, the accuracy of stated calorie information, or the ability to assess food orders and consumption in QSRs. This study evaluated the feasibility of plate waste collection in QSRs and examined children’s orders and consumption of meals from the standard and children’s menus. Additional aims were to examine if the meals ordered met healthier standards for children’s menu items and determine the accuracy of the QSR-stated energy content of foods. Methods: Fifteen QSRs, two malls, and 116 eligible parents were approached to participate in the study in 2015. Among the families recruited, children’s meal orders and consumption were analyzed using plate waste methodology, and a subsample of foods was analyzed using bomb calorimetry in 2015. Results: Two individual QSRs and one mall food court with two QSRs agreed to participate, and n = 50 participants (parents with children between the ages of 5-10 years) were recruited. Children consumed on average 519 calories, 5.7 g saturated fat, 957 mg sodium, 3.7 g fiber, and 22.7 g sugar. Children ordered and consumed significantly fewer calories and less sodium and sugar with meals ordered exclusively from the children’s menu compared with the standard menu. Overall there were no significant differences between the measured and stated energy contents of the QSR foods. Conclusions: Conducting plate waste research in QSRs is feasible and there is concordance with stated calorie information. Consuming foods exclusively from the children’s menu may help limit overconsumption in QSRs. Electronic supplementary material The online version of this article (doi:10.1186/s12889-017-4171-5) contains supplementary material, which is available to authorized users

Process evaluation outcomes from a global child obesity prevention intervention

Background: While it is acknowledged that child obesity interventions should cover multiple ecological levels (downstream, midstream and upstream) to maximize their effectiveness, there is a lack of evaluation data to guide the development and implementation of such efforts. To commence addressing this knowledge gap, the present study provides process evaluation data relating to the experiences of groups implementing the EPODE approach to child obesity prevention in various locations around the world. The aim of this exploratory study was to investigate the barriers and facilitators to program implementation in program sites around the world to assist in developing strategies to enhance program outcomes. Methods: An online survey that included open-ended questions was distributed to the 25 EPODE programs in operation at the time of the survey (May 2012). The survey items asked respondents to comment on those aspects of program implementation that they found challenging and to suggest areas for future improvement. Eighteen programs representing 14 countries responded to the request to participate in the survey, yielding a 72% response rate. The responses were analyzed via the constant comparative method using NVivo qualitative data analysis software.Results: The main concerns of the various EPODE programs were their ability to secure ongoing funding and their access to evidence-based intervention methods and policy advice relating to relationships with third parties. These issues were in turn impacted by other factors, including (i) access to user-friendly information relating to the range of intervention strategies available and appropriate evaluation measures; (ii) assistance with building and maintaining stakeholder relationships; and (iii) assurance of the quality, independence, and transparency of policies and practices. Conclusions: The findings are facilitating the ongoing refinement of the EPODE approach. In particular, standardized and tailored information packages are being made available to advise program members of (i) the various evaluation methods and tools at their disposal and (ii) methods of acquiring private partner support. Overall, the study results relating to the types of issues encountered by program members are likely to be useful in guiding the future design and implementation of multi-level initiatives seeking to address other complex and intractable health-related problems

Development and testing of the BONES physical activity survey for young children

<p>Abstract</p> <p>Background</p> <p>Weight-bearing and high intensity physical activities are particularly beneficial for stimulating bone growth in children given that bone responds favorably to mechanical load. While it is important to assess the contribution and impact of weight-bearing physical activity on health outcomes, measurement tools that quantify and provide information on these activities separately from overall physical activity are limited. This study describes the development and evaluation of a pictorial physical activity survey (PAS) that measures children's participation and knowledge of high-intensity, weight-bearing ("bone smart") physical activity.</p> <p>Methods</p> <p>To test reliability, two identical sets of the PAS were administered on the same day to 41 children (mean age 7.1 ± 0.8 years; 63% female) and compared. To test validity, accelerometry data from 40 children (mean age 7.7 ± 0.8 years; 50% female) were compared to data provided by the PAS. Agreements between categorical and ordinal items were assessed with Kappa statistics; agreements between continuous indices were assessed with Spearman's correlation tests.</p> <p>Results</p> <p>The subjects produced reliable results in all 10 physical activity participation items (κ range: 0.36-0.73, all p < 0.05), but less reliable in answering if the physical activities were "bone smart" (κ range: -0.04-0.66). Physical activity indices, including metabolic equivalent time and weight-bearing factors, were significant in test-retest analyses (Spearman's <it>r </it>range: 0.57-0.74, all p < 0.001). Minutes of very vigorous activity from the accelerometer were associated with the self-reported weight-bearing activity, moderate-high, and high activity scores from the PAS (Spearman's <it>r </it>range: 0.47-0.48, all p < 0.01). However, accelerometer counts, counts per minute, and minutes of moderate-vigorous and vigorous activity were not associated with the PAS scores.</p> <p>Conclusions</p> <p>Together, the results of these studies suggest that the PAS has acceptable test-retest reliability, but limited validity for early elementary school children. This survey demonstrates a first step towards developing a questionnaire that measures high intensity, weight-bearing activity in schoolchildren.</p

Developing self-regulation for dietary temptations: intervention effects on physical, self-regulatory and psychological outcomes

We aimed to investigate whether a self-regulatory skills intervention can improve weight loss-related outcomes. Fifty-five participants (M BMI = 32.60 ± 4.86) were randomized into self-regulation training and advice groups and received two training workshops and weekly practice tasks. The self-regulation training group was trained to use six self-regulatory skills: Delayed gratification, thought control, goal setting, self-monitoring, mindfulness, and coping. The advice group received dietary and physical activity advice for weight loss. Physical, self-regulatory, and psychological measures were taken at baseline, end of intervention (week 8) and at follow-up (week 12). Using intention-to-treat analysis, weight, waist circumference, body fat and body mass index (BMI) were significantly reduced at follow-up for both groups. There were significant increases in all six self-regulatory skills and the psychological measures of self-efficacy, self-regulatory success, and physical self-worth for both groups. Results indicate that self-regulatory skills training might be as effective as dietary and physical activity advice in terms of weight loss and related outcomes

The development of a network for community-based obesity prevention: the CO-OPS Collaboration

Background: Community-based interventions are a promising approach and an important component of a comprehensive response to obesity. In this paper we describe the Collaboration of COmmunity-based Obesity Prevention Sites (CO-OPS Collaboration) in Australia as an example of a collaborative network to enhance the quality and quantity of obesity prevention action at the community level. The core aims of the CO-OPS Collaboration are to: identify and analyse the lessons learned from a range of community-based initiatives aimed at tackling obesity, and; to identify the elements that make community-based obesity prevention initiatives successful and share the knowledge gained with other communities.Methods: Key activities of the collaboration to date have included the development of a set of Best Practice Principles and knowledge translation and exchange activities to promote the application (or use) of evidence, evaluation and analysis in practice.Results: The establishment of the CO-OPS Collaboration is a significant step toward strengthening action in this area, by bringing together research, practice and policy expertise to promote best practice, high quality evaluation and knowledge translation and exchange. Future development of the network should include facilitation of furtherevidence generation and translation drawing from process, impact and outcome evaluation of existing communitybased interventions.Conclusions: The lessons presented in this paper may help other networks like CO-OPS as they emerge around the globe. It is important that networks integrate with each other and share the experience of creating these networks.<br /

Developing a Research Agenda for Cardiovascular Disease Prevention in High-Risk Rural Communities

The National Institutes of Health convened a workshop to engage researchers and practitioners in dialogue on research issues viewed as either unique or of particular relevance to rural areas, key content areas needed to inform policy and practice in rural settings, and ways rural contexts may influence study design, implementation, assessment of outcomes, and dissemination. Our purpose was to develop a research agenda to address the disproportionate burden of cardiovascular disease (CVD) and related risk factors among populations living in rural areas. Complementary presentations used theoretical and methodological principles to describe research and practice examples from rural settings. Participants created a comprehensive CVD research agenda that identified themes and challenges, and provided 21 recommendations to guide research, practice, and programs in rural areas