Understanding the potential and challenges of adenoma treatment as a prevention opportunity: Insights from the BeWEL formative study

Objectives. To explore prevention opportunities presented by colorectal adenoma diagnosis and inform engagement strategies for the BeWEL study (body weight and physical activity lifestyle intervention for colorectal cancer screening participants who have undergone adenoma removal). Methods. Qualitative study comprising 4 purposively sampled focus groups conducted in urban and rural areas in Tayside, Scotland, with different deprivation levels. Participants were men and women (n=17) aged 50-74 with BMI>25 kg/m2 with removal of adenoma detected by colorectal cancer screening. Results. Adenoma diagnosis presents both opportunities and challenges for prevention. Some patients perceived adenoma as minor and not sufficiently motivating to act as a ‘teachable moment’. Patients had low awareness of the relationship between adenoma and lifestyle factors, and received little information on prevention during screening and treatment. Consequently they interpreted post-treatment ‘all clear’ messages as validation of existing lifestyles, and did not see the relevance of prevention advice. Receptiveness increased when the association between lifestyle, adenoma recurrence and other illness was explained. Conclusion. The study illustrates the value of exploratory research into patient understanding to improve communications and health services. Without unduly worrying patients, professionals should explain how to reduce risk of adenoma, cancer and other diseases, particularly through diet, physical activity and weight reduction

Evaluation of the impact of a school gardening intervention on children's fruit and vegetable intake: a randomised controlled trial.

Background: Current academic literature suggests that school gardening programmes can provide an interactive environment with the potential to change children’s fruit and vegetable intake. This is the first cluster randomised controlled trial (RCT) designed to evaluate whether a school gardening programme can have an effect on children’s fruit and vegetable intake. Methods: The trial included children from 23 schools; these schools were randomised into two groups, one to receive the Royal Horticultural Society (RHS)-led intervention and the other to receive the less involved Teacher-led intervention. A 24-hour food diary (CADET) was used to collect baseline and follow-up dietary intake 18 months apart. Questionnaires were also administered to evaluate the intervention implementation. Results: A total of 641 children completed the trial with a mean age of 8.1 years (95% CI: 8.0, 8.4). The unadjusted results from multilevel regression analysis revealed that for combined daily fruit and vegetable intake the Teacher-led group had a higher daily mean change of 8 g (95% CI: −19, 36) compared to the RHS-led group -32 g (95% CI: −60, −3). However, after adjusting for possible confounders this difference was not significant (intervention effect: −40 g, 95% CI: −88, 1; p = 0.06). The adjusted analysis of process measures identified that if schools improved their gardening score by 3 levels (a measure of school gardening involvement - the scale has 6 levels from 0 ‘no garden’ to 5 ‘community involvement’), irrespective of group allocation, children had, on average, a daily increase of 81 g of fruit and vegetable intake (95% CI: 0, 163; p = 0.05) compared to schools that had no change in gardening score. Conclusions: This study is the first cluster randomised controlled trial designed to evaluate a school gardening intervention. The results have found very little evidence to support the claims that school gardening alone can improve children’s daily fruit and vegetable intake. However, when a gardening intervention is implemented at a high level within the school it may improve children’s daily fruit and vegetable intake by a portion. Improving children’s fruit and vegetable intake remains a challenging task

‘Do i care?’ young adults' recalled experiences of early adolescent overweight and obesity: a qualitative study

<p>Objective: Individual behaviour change to reduce obesity requires awareness of, and concern about, weight. This paper therefore describes how young adults, known to have been overweight or obese during early adolescence, recalled early adolescent weight-related awareness and concerns. Associations between recalled concerns and weight-, health- and peer-related survey responses collected during adolescence are also examined.</p> <p>Design: Qualitative semi-structured interviews with young adults; data compared with responses to self-report questionnaires obtained in adolescence.</p> <p>Participants: A total of 35 participants, purposively sub-sampled at age 24 from a longitudinal study of a school year cohort, previously surveyed at ages 11, 13 and 15. Physical measures during previous surveys allowed identification of participants with a body mass index (BMI) indicative of overweight or obesity (based on British 1990 growth reference) during early adolescence. Overall, 26 had been obese, of whom 11 had BMI99.6th centile, whereas 9 had been overweight (BMI=95th–97.9th centile).</p> <p>Measures: Qualitative interview responses describing teenage life, with prompts for school-, social- and health-related concerns. Early adolescent self-report questionnaire data on weight-worries, self-esteem, friends and victimisation (closed questions).</p> <p>Results: Most, but not all recalled having been aware of their overweight. None referred to themselves as having been obese. None recalled weight-related health worries. Recollection of early adolescent obesity varied from major concerns impacting on much of an individual's life to almost no concern, with little relation to actual severity of overweight. Recalled concerns were not clearly patterned by gender, but young adult males recalling concerns had previously reported more worries about weight, lower self-esteem, fewer friends and more victimisation in early adolescence; no such pattern was seen among females. Conclusion: The popular image of the unhappy overweight teenager was not borne out. Many obese adolescents, although well aware of their overweight recalled neither major dissatisfaction nor concern. Weight-reduction behaviours are unlikely in such circumstances.</p&gt

The generalized cusp in ABJ(M) N = 6 Super Chern-Simons theories

We construct a generalized cusped Wilson loop operator in N = 6 super Chern-Simons-matter theories which is locally invariant under half of the supercharges. It depends on two parameters and interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines, representing a natural generalization of the quark-antiquark potential in ABJ(M) theories. For particular choices of the parameters we obtain 1/6 BPS configurations that, mapped on S^2 by a conformal transformation, realize a three-dimensional analogue of the wedge DGRT Wilson loop of N = 4. The cusp couples, in addition to the gauge and scalar fields of the theory, also to the fermions in the bifundamental representation of the U(N)xU(M) gauge group and its expectation value is expressed as the holonomy of a suitable superconnection. We discuss the definition of these observables in terms of traces and the role of the boundary conditions of fermions along the loop. We perform a complete two-loop analysis, obtaining an explicit result for the generalized cusp at the second non-trivial order, from which we read off the interaction potential between heavy 1/2 BPS particles in the ABJ(M) model. Our results open the possibility to explore in the three-dimensional case the connection between localization properties and integrability, recently advocated in D = 4.Comment: 53 pages, 10 figures, added references, this is the version appeared on JHE

Comparison of metal-dependent catalysis by HIV-1 and ASV integrase proteins using a new and rapid, moderate throughput assay for joining activity in solution

<p>Abstract</p> <p>Background</p> <p>HIV-1 integrase (IN) is an attractive target for the development of drugs to treat AIDS, and inhibitors of this viral enzyme are already in the clinic. Nevertheless, there is a continuing need to devise new approaches to block the activity of this viral protein because of the emergence of resistant strains. To facilitate the biochemical analysis of wild-type IN and its derivatives, and to measure the potency of prospective inhibitory compounds, a rapid, moderate throughput solution assay was developed for IN-catalyzed joining of viral and target DNAs, based on the detection of a fluorescent tag.</p> <p>Results</p> <p>A detailed, step-by-step description of the new joining assay is provided. The reactions are run in solution, the products captured on streptavidin beads, and activity is measured by release of a fluorescent tag. The procedure can be scaled up for the analysis of numerous samples, and is substantially more rapid and sensitive than the standard radioactive gel methods. The new assay is validated and its utility demonstrated via a detailed comparison of the Mg⁺⁺- and Mn⁺⁺-dependent activities of the IN proteins from human immunodeficiency virus type 1 (HIV-1) and the avian sarcoma virus (ASV). The results confirm that ASV IN is considerably more active than HIV-1 IN, but with both enzymes the initial rates of joining, and the product yields, are higher in the presence of Mn⁺⁺than Mg⁺⁺. Although the pH optima for these two enzymes are similar with Mn⁺⁺, they differ significantly in the presence of Mg⁺⁺, which is likely due to differences in the molecular environment of the binding region of this physiologically relevant divalent cation. This interpretation is strengthened by the observation that a compound that can inhibit HIV-1 IN in the presence of either metal cofactors is only effective against ASV in the presence of Mn⁺⁺.</p> <p>Conclusion</p> <p>A simplified, assay for measuring the joining activity of retroviral IN in solution is described, which offers several advantages over previous methods and the standard radioactive gel analyses. Based on comparisons of signal to background ratios, the assay is 10–30 times more sensitive than gel analysis, allows more rapid and accurate biochemical analyses of IN catalytic activity, and moderate throughput screening of inhibitory compounds. The assay is validated, and its utility demonstrated in a comparison of the metal-dependent activities of HIV-1 and ASV IN proteins.</p

Designing an intervention to help people with colorectal adenomas reduce their intake of red and processed meat and increase their levels of physical activity: a qualitative study

Background: most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients' preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial.Methods: patients aged 60-74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared.Results: two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population.Conclusion: this study has demonstrated the difficulties involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to individuals, the lack of knowledge about the aetiology of colon cancer and the lack of motivation to change behaviour are critical factors

Problems recruiting and retaining postnatal women to a pilot randomised controlled trial of a web-delivered weight loss intervention ISRCTN48086713 ISRCTN

Abstract Objective This paper highlights recruitment and retention problems identified during a pilot randomised controlled trial and process evaluation. The pilot trial aimed to evaluate the feasibility and acceptability of a web-delivered weight loss intervention for postnatal women and associated trial protocol. Results General practice database searches revealed low rates of eligible postnatal women per practice. 16 (10%) of the 168 identified women were recruited and randomised, seven to the intervention and nine to the control. 57% (4/7) of the intervention women completed 3 month follow-up measurements in comparison to 56% (5/9) in the control group. By 12 months, retention in the intervention group was 43% (3/7), with 2/7 women active on the website, in comparison to 44% (4/9) of the control group. Interview findings revealed the web as an acceptable method for delivery of the intervention, with the suggestion of an addition of a mobile application. Alternative recruitment strategies, using health visitor appointments, midwifery departments or mother and baby/toddler groups, should be explored. Greater involvement of potential users should enable better recruitment methods to be developed. Trial registration ISRCTN: ISRCTN48086713, Registered 26 October 201

A New Role for Translation Initiation Factor 2 in Maintaining Genome Integrity

Escherichia coli translation initiation factor 2 (IF2) performs the unexpected function of promoting transition from recombination to replication during bacteriophage Mu transposition in vitro, leading to initiation by replication restart proteins. This function has suggested a role of IF2 in engaging cellular restart mechanisms and regulating the maintenance of genome integrity. To examine the potential effect of IF2 on restart mechanisms, we characterized its influence on cellular recovery following DNA damage by methyl methanesulfonate (MMS) and UV damage. Mutations that prevent expression of full-length IF2-1 or truncated IF2-2 and IF2-3 isoforms affected cellular growth or recovery following DNA damage differently, influencing different restart mechanisms. A deletion mutant (del1) expressing only IF2-2/3 was severely sensitive to growth in the presence of DNA-damaging agent MMS. Proficient as wild type in repairing DNA lesions and promoting replication restart upon removal of MMS, this mutant was nevertheless unable to sustain cell growth in the presence of MMS; however, growth in MMS could be partly restored by disruption of sulA, which encodes a cell division inhibitor induced during replication fork arrest. Moreover, such characteristics of del1 MMS sensitivity were shared by restart mutant priA300, which encodes a helicase-deficient restart protein. Epistasis analysis indicated that del1 in combination with priA300 had no further effects on cellular recovery from MMS and UV treatment; however, the del2/3 mutation, which allows expression of only IF2-1, synergistically increased UV sensitivity in combination with priA300. The results indicate that full-length IF2, in a function distinct from truncated forms, influences the engagement or activity of restart functions dependent on PriA helicase, allowing cellular growth when a DNA–damaging agent is present

Measures of low food variety and poor dietary quality in a cross-sectional study of London school children.

BACKGROUND/OBJECTIVES: The use of simple screening tools to measure nutritional adequacy in a public health context in developed countries are currently lacking. We explore the relationship between food variety and nutrient intake of London school children using a simple tool with potential use for screening for inadequate diets. SUBJECTS/METHODS: A cross-sectional survey was carried out in 2010. The survey included 2579 children aged 7-10 years in 52 primary schools in East London in the United Kingdom. The analysis included 2392 children (93% of the original sample). Food variety was assessed as the total number of listed foods recorded over 24 h using the validated Child and Diet Assessment Tool (CADET) comprising 115 listed foods divided into 16 food categories. Dietary quality was determined by the proportion of children meeting recommended intakes of individual micronutrients, namely, calcium, iron, zinc, folate, vitamin A and vitamin C. RESULTS: The mean number of CADET-listed foods consumed daily by children was 17.1 (95% CI: 16.8, 17.5). Children who consumed fewer than 11 foods on the collection day had particularly low nutrient intakes. Children consuming three different vegetables and two different fruits on average consumed 19-20 listed foods. It was estimated between 4 and 20% of children did not meet the recommended levels for individual micronutrients during the period of data collection. CONCLUSIONS: A simple method using food counts to assess daily food variety may help public health nutritionists identify groups of children at risk of inadequate diets