Awareness of lifestyle and colorectal cancer risk:findings from the BeWEL study

It is estimated that 47% of colorectal cancers (CRC) could be prevented by appropriate lifestyles. This study aimed to identify awareness of the causes of CRC in patients who had been diagnosed with a colorectal adenoma through the Scottish Bowel Screening Programme and subsequently enrolled in an intervention trial (using diet and physical activity education and behavioural change techniques) (BeWEL). At baseline and 12-month follow-up, participants answered an open-ended question on factors influencing CRC development. Of the 329 participants at baseline, 40 (12%) reported that they did not know any risk factors and 36 (11%) failed to identify specific factors related to diet and activity. From a potential knowledge score of 1 to 6, the mean score was 1.5 (SD 1.1, range 0 to 5) with no difference between intervention and control groups. At follow-up, the intervention group had a significantly greater knowledge score and better weight loss, diet, and physical activity measures than the control group. Awareness of relevant lifestyle factors for CRC remains low in people at increased risk of the disease. Opportunities within routine NHS screening to aid the capability (including knowledge of risk factors) of individuals to make behavioural changes to reduce CRC risk deserve exploration.Additional co-author: The BeWEL team. The BeWEL Team consists of Shaun Treweek, Fergus Daly, Jill Belch, Jackie Rodger, Alison Kirk, Anne Ludbrook, Petra Rauchhaus, Patricia Norwood, Joyce Thompson, and Jane Wardle

Meeting the challenges of recruitment to multicentre, community-based, lifestyle-change trials : a case study of the BeWEL trial

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Resistance to the Antimicrobial Peptide Polymyxin Requires Myristoylation of Escherichia Coli and Salmonella Typhimurium Lipid A

Attachment of positively charged, amine-containing residues such as 4-amino-4-deoxy-L-arabinose (L-Ara4N) and phosphoethanolamine (pEtN) to Escherichia coli and Salmonella typhimurium lipid A is required for resistance to the cationic antimicrobial peptide, polymyxin. In an attempt to discover additional lipid A modifications important for polymyxin resistance, we generated polymyxin-sensitive mutants of an E. coli pmrAC strain, WD101. A subset of polymyxin-sensitive mutants produced a lipid A that lacked both the 3′-acyloxyacyl-linked myristate (C14) and L-Ara4N, even though the necessary enzymatic machinery required to synthesize L-Ara4N-modified lipid A was present. Inactivation of lpxM in both E. coli and S. typhimurium resulted in the loss of L-Ara4N addition, as well as, increased sensitivity to polymyxin. However, decoration of the lipid A phosphate groups with pEtN residues was not effected in lpxM mutants. In summary, we demonstrate that attachment of L-Ara4N to the phosphate groups of lipid A and the subsequent resistance to polymyxin is dependent upon the presence of the secondary linked myristoyl group

Electrical Stimulation Modulates High γ Activity and Human Memory Performance.

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62-118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with poor memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation

Variability and effectiveness of comparator group interventions in smoking cessation trials : A systematic review and meta-analysis

Funding: This work was funded by Cancer Research UK (application number C50862/A18446). The systematic review protocol was previously peer-reviewed by Cancer Research UK as part of the funding process. The funder had no role in protocol design, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

Feasibility study to assess the impact of a lifestyle intervention (‘LivingWELL’) in people having an assessment of their family history of colorectal or breast cancer

Objectives To assess the feasibility of delivering and evaluating a weight management (WM) programme for overweight patients with a family history (FH) of breast cancer (BC) or colorectal cancer (CRC).  Study design A two-arm (intervention vs usual care) randomised controlled trial. Setting National Health Service (NHS) Tayside and NHS Grampian.  Participants People with a FH of BC or CRC aged≥18 years and body mass index of ≥25 kg/m2 referred to NHS genetic services.  Intervention Participants were randomised to a control (lifestyle booklet) or 12-week intervention arm where they were given one face-to-face counselling session, four telephone consultations and web-based support. A goal of 5% reduction in body weight was set, and a personalised diet and physical activity (PA) programme was provided. Behavioural change techniques (motivational interviewing, action and coping plans and implementation intentions) were used.  Primary outcome Feasibility measures: recruitment, programme implementation, fidelity measures, achieved measurements and retention, participant satisfaction assessed by questionnaire and qualitative interviews.  Secondary outcomes Measured changes in weight and PA and reported diet and psychosocial measures between baseline and 12-week follow-up. Results Of 480 patients approached, 196 (41%) expressed interest in the study, and of those, 78 (40%) patients were randomised. Implementation of the programme was challenging within the time allotted and fidelity to the intervention modest (62%). Qualitative findings indicated the programme was well received. Questionnaires and anthropometric data were completed by >98%. Accelerometer data were attained by 84% and 54% at baseline and follow-up, respectively. Retention at 12 weeks was 76%. Overall, 36% of the intervention group (vs 0% in control) achieved 5% weight loss. Favourable increases in PA and reduction in dietary fat were also reported.  Conclusions A lifestyle programme for people with a family history of cancer is feasible to conduct and acceptable to participants, and indicative results suggest favourable outcomes.  Trial registration number ISRCTN13123470; Pre-results

Proteomic comparison of selective breeding and growth hormone transgenesis in fish:Unique pathways to enhanced growth

Open Access funded by Biotechnology and Biological Sciences Research CouncilPeer reviewedPublisher PD

Upper-Room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission

Background Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. Methods and Findings For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. Conclusions Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings

Feasibility study to assess the delivery of a lifestyle intervention (TreatWELL) for patients with colorectal cancer undergoing potentially curative treatment

Objectives To assess the feasibility of delivering and evaluating a lifestyle programme for patients with colorectal cancer undergoing potentially curative treatments.Study design Non-randomised feasibility trial.Setting National Health Service (NHS) Tayside.Participants Adults with stage I–III colorectal cancer.Intervention The programme targeted smoking, alcohol, physical activity, diet and weight management. It was delivered in three face-to-face counselling sessions (plus nine phone calls) by lifestyle coaches over three phases (1: presurgery, 2: surgical recovery and 3: post-treatment recovery).Primary outcome Feasibility measures (recruitment, retention, programme implementation, achieved measures, fidelity, factors affecting protocol adherence and acceptability).Secondary outcomes Measured changes in body weight, waist circumference, walking and self-reported physical activity, diet, smoking, alcohol intake, fatigue, bowel function and quality of life.Results Of 84 patients diagnosed, 22 (26%) were recruited and 15 (18%) completed the study. Median time for intervention delivery was 5.5 hours. Coaches reported covering most (>70%) of the intervention components but had difficulties during phase 2. Evaluation measures (except walk test) were achieved by all participants at baseline, and most

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD