Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

The World Starts With Me: using intervention mapping for the systematic adaptation and transfer of school-based sexuality education from Uganda to Indonesia

Evidence-based health promotion programmes, including HIV/AIDS prevention and sexuality education programmes, are often transferred to other cultures, priority groups and implementation settings. Challenges in this process include the identification of retaining core elements that relate to the programme’s effectiveness while making changes that enhances acceptance in the new context and for the new priority group. This paper describes the use of a systematic approach to programme adaptation using a case study as an example. Intervention Mapping, a protocol for the development of evidence-based behaviour change interventions, was used to adapt the comprehensive school-based sexuality education programme ‘The World Starts With Me’. The programme was developed for a priority population in Uganda and adapted to a programme for Indonesian secondary school students. The approach helped to systematically address the complexity and challenges of programme adaptation and to find a balance between preservation of essential programme elements (i.e. logic models) that may be crucial to the programme’s effectiveness, including key objectives and theoretical behaviour change methods, and the adaptation of the programme to be acceptable to the new priority group and the programme implementers

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Receptor-Mediated Enhancement of Beta Adrenergic Drug Activity by Ascorbate In Vitro and In Vivo

RATIONALE: Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. OBJECTIVES: Extending this work to beta 2 adrenergic systems in vitro and in vivo. METHODS: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuterol with and without ascorbate was tested on horses with heaves and sheep with carbachol-induced bronchoconstriction. MEASUREMENTS: Binding constants for ascorbate binding to beta adrenergic receptor were derived from concentration-dependent spectral shifts. Dose- dependence curves were obtained for the relaxation of pre-contracted trachealis preparations due to beta agonists in the presence and absence of varied ascorbate. Tachyphylaxis and fade were also measured. Dose response curves were determined for the effect of albuterol plus-and-minus ascorbate on airway resistance in horses and sheep. MAIN RESULTS: Ascorbate binds to the beta 2 adrenergic receptor at physiological concentrations. The receptor recycles dehydroascorbate. Physiological and supra-physiological concentrations of ascorbate enhance submaximal epinephrine and isoproterenol relaxation of trachealis, producing a 3-10-fold increase in sensitivity, preventing tachyphylaxis, and reversing fade. In vivo, ascorbate improves albuterol's effect on heaves and produces a 10-fold enhancement of albuterol activity in "asthmatic" sheep. CONCLUSIONS: Ascorbate enhances beta-adrenergic activity via a novel receptor-mediated mechanism; increases potency and duration of beta adrenergic agonists effective in asthma and COPD; prevents tachyphylaxis; and reverses fade. These novel effects are probably caused by a novel mechanism involving phosphorylation of aminergic receptors and have clinical and drug-development applications

Head and Neck Lymphomas: Tip of the Iceberg?

ABSTRACT Background: Lymphomas comprise around 5% of all head and neck neoplasms and is the second most common extra nodal non hodgkin's lymphoma (NHL). However there is sporadic data on this entity from the subcontinent and hence we undertook this study. Methodology: This retrospective observational study was conducted at a tertiary care oncology center in India on diagnosed cases of NHL between January 2007 and December 2013. All patients were diagnosed based on histopathology and immunohistochemistry. Staging work up was done in all patients. Patients were considered as primary Head and Neck lymphomas if there was head and neck as the predominant site with or without regional lymph node involvement. Results: A total of 39 patients were studied. The age at presentation ranged from 29 to 78 years. The most common site of presentation was oral cavity (26%; n=10), followed by parotid and thyroid (18% each; n=7), eye (12%, n=5), maxilla (8%; n=3), paranasal sinuses (8%; n-=3) cheek (8%, n=3), and nasal cavity (2%, n=1). 41% (n=16) cases were in stage I, 43% (n=17) in stage II, 3% (n=1) in stage III, and 13% (n=5) were in stage IV. Most common histology was DLBCL (71%; n=28), followed by plasmablastic (10%; n=4), marginal zone (8%, n=3), mantle cell (3%; n=1), follicular lymphomas (5%; n=2), and NK/T cell lymphoma (3%; n=1). Most of the patients were of low risk (67%; n=26), followed by intermediate (23%; n=9), and high risk (10%; n=4). Patients were treated with anthracycline based chemotherapy +/-radiotherapy. In this study, stage I and stage II patients had a better prognosis and overall survival, median OS 28 months and 11 months, respectively. In stage III and IV, it was 7 and 3 months, respectively. According to site, the best median overall survival was seen with parotid (27 m), paranasal sinus (26m), and oral cavity (23 m), followed by thyroid (18 m) nasal cavity (17 m), maxilla (11 m), eye (8 m), and cheek (7 m)

Alternative mRNA Editing in Trypanosomes Is Extensive and May Contribute to Mitochondrial Protein Diversity

The editing of trypanosome mitochondrial mRNAs produces transcripts necessary for mitochondrial functions including electron transport and oxidative phosphorylation. Precursor-mRNAs are often extensively edited by specific uridine insertion or deletion that is directed by small guide RNAs (gRNAs). Recently, it has been shown that cytochrome c oxidase subunit III (COXIII) mRNAs can be alternatively edited to encode a novel mitochondrial membrane protein composed of a unique hydrophilic N-terminal sequence of unknown function and the C-terminal hydrophobic segment of COXIII. To extend the analysis of alternative editing in Trypanosoma brucei we have constructed libraries with over 1100 full-length mitochondrial cDNAs and the sequences of over 1200 gRNA genes. Using this data, we show that alternative editing of COXIII, ATPase subunit 6 (A6), and NADH dehydrogenase subunits 7, 8 and 9 (ND7, 8, 9) mRNAs can produce novel open reading frames (ORFs). Several gRNAs potentially responsible for the alternative editing of these mRNAs were also identified. These findings show that alternative editing of mitochondrial mRNAs is common in T. brucei and expands the diversity of mitochondrial proteins in these organisms

Systematic development of a self-regulation weight-management intervention for overweight adults

Background. This paper describes the systematic development of an intervention for the prevention of obesity among overweight adults. Its development was guided by the six steps of Intervention Mapping (IM), in which the establishment of program needs, objectives and methods is followed by development of the intervention and an implementation and evaluation plan. Methods. Weight gain prevention can be achieved by making small changes in dietary intake (DI) or physical activity (PA). The intervention objectives, derived from self-regulation theory, were to establish goal-oriented behaviour. They were translated into a computer-tailored Internet-delivered intervention consisting of four modules. The intervention includes strategies to target the main determinants of self-regulation, such as feedback and action planning. The first module is intended to ensure adults' commitment to preventing weight gain, choosing behaviour change and action initiation. The second and third modules are intended to evaluate behaviour change, and to adapt action and coping plans. The fourth module is intended to maintain self-regulation of body weight without use of the program. The intervention is being evaluated for its efficacy in an RCT, whose protocol is described in this paper. Primary outcomes are weight, waist circumference and skin-fold thickness. Other outcomes are DI, PA, cognitive mediators and self-regulation skills. Discussion. The IM protocol helped us integrating insights from various theories. The performance objectives and methods were guided by self-regulation theory but empirical evidence with regard to the effectiveness of theoretical methods was limited. Sometimes, feasibility issues made it necessary to deviate from the original, theory-based plans. With this paper, we provide transparency with regard to intervention development and evaluation. Trial registration. NTR1862

Trial baseline characteristics of a cluster randomised controlled trial of a school-located obesity prevention programme; the Healthy Lifestyles Programme (HeLP) trial

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background We have developed a healthy lifestyles programme (HeLP) for primary school aged children (9–10 years), currently being evaluated in a definitive cluster randomised controlled trial. This paper descriptively presents the baseline characteristics of trial children (BMI, waist circumference, % body fat, diet and physical activity) by gender, cluster level socio-economic status, school size and time of recruitment into the trial. Methods Schools were recruited from across the South West of England and allocated 1:1 to either intervention (HeLP) or control (usual practice) stratified by the proportion of children eligible for free school meals (FSM, 1 Year 5 class). The primary outcome is change in body mass index standard deviation score (BMI sds) at 24 months post-randomisation. Secondary outcomes are BMI sds at 18 months, waist circumference and percentage body fat sds at 18 and 24 months, proportion of children classified as underweight, overweight and obese at 18 and 24 months, physical activity (for a sub-sample) and food intake at 18 months. Results At baseline 11.4% and 13.6% of children were categorised as overweight or obese respectively. A higher percentage of girls than boys (25.3% vs 24.8%) and children from schools in FSM category 2 (28.2% vs 23.2%) were overweight or obese. Children were consuming a mean (range) of 4.15 (0–13) energy dense snacks (EDS) and 3.23 (0–9) healthy snacks (HS) per day with children from schools in FSM category 2 consuming more EDS and negative food markers and less HS and positive food markers. Children spent an average 53.6 min per day (11.9 to 124.8) in MVPA and thirteen hours (779.3 min) per day (11 h to 15 h) doing less than ‘light’ intensity activity. Less than 5% of children achieved the Departments of Health’s recommendation of 60 min of MVPA every day. Conclusion We have excellent completeness of baseline data for all measures and have achieved compliance to accelerometry not seen before in other large scale studies. Our anthropometric baseline data is representative of local and national data for children this age and reflects the gender and socio-economic variations expected of children this age in relation to physical activity and weight status.The definitive trial of HeLP is funded by the UK National Institute for Health Research (NIHR) Public Health Research Programme (10/3010/01) and a full report will be published on the NIHR website. Intervention materials and delivery was funded by the Peninsula College of Medicine and Dentistry. PenCLAHRC provided methodological support during the transition from the exploratory trial to the definitive evaluation