Expression profiling indicating low selenium-sensitive microRNA levels linked to cell cycle and cell stress response pathways in the CaCo-2 cell line

Se is an essential micronutrient for human health, and fluctuations in Se levels and the potential cellular dysfunction associated with it may increase the risk for disease. Although Se has been shown to influence several biological pathways important in health, little is known about the effect of Se on the expression of microRNA (miRNA) molecules regulating these pathways. To explore the potential role of Se-sensitive miRNA in regulating pathways linked with colon cancer, we profiled the expression of 800 miRNA in the CaCo-2 human adenocarcinoma cell line in response to a low-Se (72 h at <40 nm) environment using nCounter direct quantification. These data were then examined using a range of in silico databases to identify experimentally validated miRNA-mRNA interactions and the biological pathways involved. We identified ten Se-sensitive miRNA (hsa-miR-93-5p, hsa-miR-106a-5p, hsa-miR-205-5p, hsa-miR-200c-3p, hsa-miR-99b-5p, hsa-miR-302d-3p, hsa-miR-373-3p, hsa-miR-483-3p, hsa-miR-512-5p and hsa-miR-4454), which regulate 3588 mRNA in key pathways such as the cell cycle, the cellular response to stress, and the canonical Wnt/β-catenin, p53 and ERK/MAPK signalling pathways. Our data show that the effects of low Se on biological pathways may, in part, be due to these ten Se-sensitive miRNA. Dysregulation of the cell cycle and of the stress response pathways due to low Se may influence key genes involved in carcinogenesis

Combretastatin-A4 disrupts neovascular development in non-neoplastic tissue

Combretastatin-A4 phosphate (cis -CA-4) is a tubulin-binding agent currently undergoing clinical trials as an anti-tumour drug. We have investigated whether CA-4 functions as a tumour-specific anti-vascular agent using the hyperplastic thyroid as a novel in vivo model of neovascularization. CA-4 elicited pathological changes in normal tissue, manifested as the induction of multiple, discrete intravascular thrombi. These vascular-damaging effects indicate that CA-4P does not function as a tumour-specific agent but targets neovasculature irrespective of the primary angiogenic stimulus. © 2001 Cancer Research Campaign http://www.bjcancer.co

Fitting multilevel models in complex survey data with design weights: Recommendations

Abstract Background Multilevel models (MLM) offer complex survey data analysts a unique approach to understanding individual and contextual determinants of public health. However, little summarized guidance exists with regard to fitting MLM in complex survey data with design weights. Simulation work suggests that analysts should scale design weights using two methods and fit the MLM using unweighted and scaled-weighted data. This article examines the performance of scaled-weighted and unweighted analyses across a variety of MLM and software programs. Methods Using data from the 2005–2006 National Survey of Children with Special Health Care Needs (NS-CSHCN: n = 40,723) that collected data from children clustered within states, I examine the performance of scaling methods across outcome type (categorical vs. continuous), model type (level-1, level-2, or combined), and software (Mplus, MLwiN, and GLLAMM). Results Scaled weighted estimates and standard errors differed slightly from unweighted analyses, agreeing more with each other than with unweighted analyses. However, observed differences were minimal and did not lead to different inferential conclusions. Likewise, results demonstrated minimal differences across software programs, increasing confidence in results and inferential conclusions independent of software choice. Conclusion If including design weights in MLM, analysts should scale the weights and use software that properly includes the scaled weights in the estimation.</p

Chemotherapy-induced nausea and vomiting in daily clinical practice: a community hospital-based study

Background Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. This study investigated: (1) the impact of CINV on patients' health-related quality of life (HRQL) in daily clinical practice; (2) the association between patient characteristics and type of antiemetics and CINV; and (3) the role of CINV in physicians' decisions to modify antiemetic treatment. Patients and methods This prospective, multicenter study was conducted in nine general hospitals in the Netherlands. During three consecutive chemotherapy cycles, patients used a diary to record episodes of nausea, vomiting and antiemetic use. For each cycle, these ratings were made 1 day prior to and 7 days after having received chemotherapy. The influence of CINV on patients' HRQL was evaluated with the Functional Living Index-Emesis (FLIE) questionnaire at day 6 of each treatment cycle. (Changes in) antiemetic use were recorded by the treating nurse. Patient inclusion took place between May 2005 and May 2007. Results Two hundred seventy-seven patients were enrolled in the study. Acute and delayed nausea during the first treatment cycle was reported by 39% and 68% of the patients, respectively. The comparable figures for acute and delayed vomiting were 12% and 23%. During the first and subsequent treatment cycle, approximately one-third of the patients indicated that CINV had a substantial impact on their daily lives. Female patients and younger patients reported significantly more CINV than male and older patients. At all treatment cycles, patients receiving treatment with moderately emetogenic chemotherapy, containing anthracycline, reported more acute nausea than patients receiving highly emetogenic chemotherapy. Acute vomiting was associated significantly with change in (i.e., additional) antiemetic treatment. Delayed CINV did not influence antiemetic treatment. Conclusion CINV continues to be a problem that adversely affects the daily lives of patients. CINV is worse in women and in younger patients. In daily clinical practice, acute CINV, but not delayed CINV, results in changes in antiemetic treatment. In view of the effects of not only acute, but also delayed CINV on daily life, more attention should be paid to adjustment of antiemetic treatment to cover CINV complaints, later during the chemotherapy cycle

Parents’ engagement in an Australian school- and home-based group RCT to reduce children’s sitting time and promote physical activity: Transform-Us!

Session - S34 Involvement of parents in multicomponent school-based interventions targeting energy balance related behaviours among children and adolescents: Lessons learned from process evaluation: abstract S34.2Conference Theme: Promoting Healthy Eating and Activity WorldwidePURPOSE: Transform-Us! was a 3-year group RCT aiming to determine the effectiveness of strategies to reduce 8-year old Australian children’s sedentary behaviour (SB) or promote their physical activity (PA), or both (PA+SB) compared with usual practice (C) at school and home. METHOD: Process evaluation data were collected at post--‐intervention (T3) Nov/Dec 2011. Nine newsletters per year were …postprin

Synthetic RNA Silencing of Actinorhodin Biosynthesis in Streptomyces coelicolor A3(2)

We demonstrate the first application of synthetic RNA gene silencers in Streptomyces coelicolor A3(2). Peptide nucleic acid and expressed antisense RNA silencers successfully inhibited actinorhodin production. Synthetic RNA silencing was target-specific and is a new tool for gene regulation and metabolic engineering studies in Streptomyces.Peer reviewe

Extending standard testing period in honeybees to predict lifespan impacts of pesticides and heavy metals using dynamic energy budget modelling

Concern over reported honeybee (Apis mellifera spp.) losses has highlighted chemical exposure as a risk. Current laboratory oral toxicity tests in A. mellifera spp. use short-term, maximum 96 hour, exposures which may not necessarily account for chronic and cumulative toxicity. Here, we use extended 240 hour (10 day) exposures to examine seven agrochemicals and trace environmental pollutant toxicities for adult honeybees. Data were used to parameterise a dynamic energy budget model (DEBtox) to further examine potential survival effects up to 30 day and 90 day summer and winter worker lifespans. Honeybees were most sensitive to insecticides (clothianidin > dimethoate ≫ tau-fluvalinate), then trace metals/metalloids (cadmium, arsenic), followed by the fungicide propiconazole and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). LC50s calculated from DEBtox parameters indicated a 27 fold change comparing exposure from 48 to 720 hours (summer worker lifespan) for cadmium, as the most time-dependent chemical as driven by slow toxicokinetics. Clothianidin and dimethoate exhibited more rapid toxicokinetics with 48 to 720 hour LC50s changes of <4 fold. As effects from long-term exposure may exceed those measured in short-term tests, future regulatory tests should extend to 96 hours as standard, with extension to 240 hour exposures further improving realism

Strategies to promote children\u27s school based physical activity : Transform-Us! Mid-intervention findings

Session 202 - School based interventions: paper 276This journal suppl. entitled: Be Avtive 2012Many children engage in suboptimal levels of PA despite the associated health risks. Schools (n=20) in the Transform-Us! program were randomized to one of four intervention arms that target increases in children’s PA (PA), reductions in sedentary behavior (SB), both behaviors (SB+PA) or control current practice (C). This examination focuses on the PA promotion strategies employed in the PA and SB+PA arms compared with the C arm. To promote children’s PA each PA and SB+PA class was provided with sporting and circus equipment; asphalt line markings were installed at the school; and teachers were asked to encourage PA. Grade 3 children at participating schools were invited to take part in evaluation assessments including the completion of a self-report survey. Findings from the PA promotion strategy questions at baseline (Feb–June 2010), and T2 (Nov/Dec) are reported here. Children (n=425, 55% female) were asked to respond (yes/no) to five items asking about social support for PA from their class teacher, which were then summed to create a ‘teacher social support’ scale. Children were also asked to indicate if ‘there are markings on the walls or on the school playground to help us play games’ (perceived availability of line markings); if they are ‘allowed to use school sports equipment during recess and lunch breaks’ (perceived accessibility of sports equipment); and how much they like ‘the areas to play in at school’ using a 5-point Likert scale (perceived school environment). Between baseline and T2, teacher social support increased in both PA (1.7[1.4] vs 2.1[1.4]) and SB arms (1.9[1.4] vs 2.4[1.4) but declined in C (2.0[1.4] vs 1.7[1.5]). For all three arms, increases were seen in perceived availability of line markings (PA: 53.2% vs 69.4%; SB+PA: 59.3% vs 71.4%; C: 60.0% vs 69.8%); perceived accessibility of sport equipment (PA: 87.7% vs 97.2%: SB+PA: 80.7 vs 94%; C: 85.4% vs 97.6%); and perceived school environment (PA: 1.44[0.9] vs 1.42[0.8]; SB+PA: 1.5[0.8] vs 1.6[0.7]; C: 1.4[0.9] vs 1.5[0.7]) between baseline and T2. All findings were significant at a 1% probability level. At the mid-intervention time point, findings suggest that PA strategies have increased perceived availability of line markings, accessibility of sport equipment, and perceived school environment in children allocated to the PA and SB+PA arms. However, there were also unexpected increases in the C arm for three out of four items. Post-intervention findings will add to these preliminary findings