Mechanisms of improved survival from intensive followup in colorectal cancer: a hypothesis

A meta-analysis of six randomised trials demonstrated that intensive followup in colorectal cancer was associated with an absolute reduction in all-cause 5-year mortality of 10% (95% confidence interval (CI): 4–16) – however, only two percent (95% CI: 0–5) was attributable to cure from salvage re-operations. We postulate that other factors, such as increased psychological well-being and/or altered lifestyle, and/or improved treatment of coincidental disease may contribute to the remaining lives saved, and form important future research questions

Developmental exposure to lead (Pb) alters the expression of the human tau gene and its products in a transgenic animal model

Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of the tau protein in the human brain. The best known of these illnesses is Alzheimer’s disease (AD); a disease where the microtubule associated protein tau (MAPT) becomes hyperphosphorylated (lowering its binding affinity to microtubules) and aggregates within neurons in the form of neurofibrillary tangles (NFTs). In this paper we examine whether environmental factors play a significant role in tau pathogenesis. Our studies were conducted in a double mutant mouse model that expressed the human tau gene and lacked the gene for murine tau. The human tau mouse model was tested for the transgene’s ability to respond to an environmental toxicant. Pups were developmentally exposed to lead (Pb) from postnatal day (PND) 1-20 with 0.2% Pb acetate. Mice were then sacrificed at PND 20, 30, 40 and 60. Protein and mRNA levels for tau and CDK5 as well as tau phosphorylation at Ser396 were determined. In addition, the potential role of miRNA in tau expression was investigated by measuring levels of miR-34c, a miRNA that targets the mRNA for human tau, at PND20 and 50. The expression of the human tau transgene was altered by developmental exposure to Pb. This exposure also altered the expression of miR-34c. Our findings are the first of their kind to test the responsiveness of the human tau gene to an environmental toxicant and to examine an epigenetic mechanism that may be involved in the regulation of this gene’s expression

Reciprocal relationship between expression of hypoxia inducible factor 1α (HIF-1α) and the pro-apoptotic protein Bid in ex vivo colorectal cancer

Hypoxia inducible factor 1 (HIF-1) represses the transcription of pro-apoptotic bid in colorectal cancer cells in vitro. To assess the clinical relevance of this observation, HIF-1α and Bid were assessed in serial sections of 39 human colorectal adenocarcinomas by immunohistochemistry. In high HIF-1α nuclear-positive cell subpopulations, there was a significant reduction in Bid expression (ANOVA, P=0.04). Given the role of Bid in drug-induced apoptosis, these data add impetus to strategies targeting HIF-1 for therapeutic gain

Formação do professor para uso da internet : o que querem os professores

Orientadora: Profª. Drª. Gláucia da Silva BritoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Educação, Programa de Pós-Graduação em Educação. Defesa: Curitiba, 13/12/2016Inclui referências : f. 76-78Resumo: Esta pesquisa está inserida na linha de pesquisa Cultura, Escola e Ensino, do Setor de Educação da Universidade Federal do Paraná - UFPR, tendo como Área de Concentração em Educação, Cultura e Tecnologia. O fato de a tecnologia adentrar no espaço escolar vem provocando mudanças no cotidiano da sala de aula. Os professores percebem que disputam a atenção dos alunos com um elemento "invisível", mas presente - A internet. Muitos professores, ou quase todos já são usuários do ciberespaço, porém poucos fazem uso deste meio em suas aulas. Alegação de senso comum é de não estar preparado para tal utilização. A partir deste entendimento, definiu-se como problema de pesquisa: o que os professores do ensino médio, de uma escola pública, estadual, precisam em sua formação continuada para utilizar a internet em sala de aula? Como objetivo da pesquisa queremos identificar o que é necessário ser trabalhado numa formação continuada dos professores para uso da internet em sala de aula. O contexto para o desenvolvimento desta investigação dividiu-se em duas etapas, tendo como instrumento de coleta de dados um questionário, na primeira etapa da pesquisa e uma entrevista semiestruturada, realizada na segunda etapa. Participaram da pesquisa 12 professores de uma escola estadual de Curitiba/PR, que responderam de forma espontânea os questionários e destes foram selecionados 4 para participar da entrevista. A estruturação metodológica da pesquisa seguiu os princípios da pesquisa qualitativa, tomando por base os estudos de Alves-Mazzotti e Gewandsznadjer (1998), Laville e Dionne (1999), Lessard-Hébert, Goyette e Boutin (1990) e Günther (2006). O referencial teórico utilizado para a construção das reflexões sobre os envolvidos na formação do professor para uso da internet em sala de aula foram Marcelo-Garcia (1999), Lévy (1999), Moran (1997, 2001, 2011), Chantraine-Demailly (1995), Brito e Purificação (2011) e Abreu (2009) entre outros. Para a análise dos dados obtidos, utilizou-se a proposta de análise de conteúdo de Bardin (1977). Os resultados indicaram que a formação técnica é ainda a principal necessidade dos professores para ser trabalhada em cursos de formação para uso da internet em sala de aula. Dentre outros pontos que a análise apresentou, verificamos também que o grupo, embora sem ter em sua formação inicial preparação para uso da internet, já vivenciou uma prática com seus alunos. Palavras-chave: Internet. Formação continuada. Sala de aula.Abstract: The present research is inserted in the Culture, School and Education research line of the Education Sector from the Federal University of Paraná - UFPR, focusing on Education, Culture and Technology. The fact that technology entered into the school environment has been provoking changes in the daily classroom routine. Teachers noticed they vie for the attention of the students with an "invisible", but present element: the internet. Many teachers, or almost all of them are already cyberspace users, but few use it in class. Not being prepared for such usage is a common sense argument. From this understanding, it was defined the following research problem: what do high school teachers from state schools need in their lifelong learning for to use the internet in the classroom? As a research goal, we look forward to identifying what it needs to be addressed in lifelong learning courses for teachers regarding the internet use in the classroom. The context of this research development was divided into two stages, having a questionnaire as a data collection instrument in the first stage and a semi-structured interview, conducted during the second phase. 12 participants from a public school from Curitiba/PR answered the questionnaires spontaneously. From those, 4 were selected to participate in the interview. This study is a qualitative approach based on Alves-Mazzotti and Gewandsznadjer (1998), Laville and Dionne (1999), Lessard-Hébert, Goyette and Boutin (1990) and Günther (2006)'s methodology. The methodological structure of the research followed the principles of qualitative research, based on the studies of Alves-Mazzotti and Gewandsznadjer (1998), Laville and Dionne (1999), Lessard-Hébert, Goyette and Boutin (1990), and Günther (2006). The theoretical framework used for setting up teacher's reflection about the internet use in the classroom was Marcelo-Garcia (1999), Lévy (1999), Moran (1997, 2001, 2011), Chantraine-Demailly (1995), Brito and Purificação (2011), Abreu (2009) and others. For data analysis, we used content analysis according to Bardin's perspective (1977). The results indicated technical training is still the main necessity to be worked out in lifelong learnig courses for teachers. We also verifyed that the group has already experienced such practice while teaching although not having an initial internet use training. Keywords: Internet. Lifelong learning. Classroom

Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

<b>Background</b> High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.<p></p> <b>Methods</b> We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.<p></p> <b>Results</b> 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to <6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of <5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.<p></p> <b>Conclusions</b> Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer

Football fans in training: the development and optimization of an intervention delivered through professional sports clubs to help men lose weight, become more active and adopt healthier eating habits

<p>Background: The prevalence of obesity in men is rising, but they are less likely than women to engage in existing weight management programmes. The potential of professional sports club settings to engage men in health promotion activities is being increasingly recognised. This paper describes the development and optimization of the Football Fans in Training (FFIT) programme, which aims to help overweight men (many of them football supporters) lose weight through becoming more active and adopting healthier eating habits.</p> <p>Methods: The MRC Framework for the design and evaluation of complex interventions was used to guide programme development in two phases. In Phase 1, a multidisciplinary working group developed the pilot programme (p-FFIT) and used a scoping review to summarize previous research and identify the target population. Phase 2 involved a process evaluation of p-FFIT in 11 Scottish Premier League (SPL) clubs. Participant and coach feedback, focus group discussions and interviews explored the utility/acceptability of programme components and suggestions for changes. Programme session observations identified examples of good practice and problems/issues with delivery. Together, these findings informed redevelopment of the optimized programme (FFIT), whose components were mapped onto specific behaviour change techniques using an evidence-based taxonomy.</p> <p>Results: p-FFIT comprised 12, weekly, gender-sensitised, group-based weight management classroom and ‘pitch-side’ physical activity sessions. These in-stadia sessions were complemented by an incremental, pedometer-based walking programme. p-FFIT was targeted at men aged 35-65 years with body mass index ≥ 27 kg/m2. Phase 2 demonstrated that participants in p-FFIT were enthusiastic about both the classroom and physical activity components, and valued the camaraderie and peer-support offered by the programme. Coaches appreciated the simplicity of the key healthy eating and physical activity messages. Suggestions for improvements that were incorporated into the optimized FFIT programme included: more varied in-stadia physical activity with football-related components; post-programme weight management support (emails and a reunion session); and additional training for coaches in SMART goal setting and the pedometer-based walking programme.</p> <p>Conclusions: The Football Fans in Training programme is highly acceptable to participants and SPL coaches, and is appropriate for evaluation in a randomised controlled trial.</p&gt

A cross-sectional study of different patterns of oral contraceptive use among premenopausal women and circulating IGF-1: implications for disease risk

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-1) is important in normal growth, development, and homeostasis. Current use of oral contraceptives (OC) decreases IGF-1 concentrations; however, the effect of past use, age/timing of use, and type of OC used on IGF-1 levels is unknown. OC are the most commonly used form of birth control worldwide. Both IGF-1 and OC use have been linked to premenopausal breast and colorectal cancers, osteoporosis and cardiovascular disease (CVD). Understanding the effects of different patterns of OC use on IGF-1 levels may offer insight into its influence on disease risk in young women.</p> <p>Methods</p> <p>In a cross-sectional study of 328 premenopausal women ages 18 to 21 and 31 to 40 we examined the relationship between different patterns of OC use and circulating IGF-1 using adjusted linear regression analysis. Information on OC use was obtained through an interviewer administered questionnaire. Plasma IGF-1 was assessed with enzyme linked immunosorbent assay (ELISA).</p> <p>Results</p> <p>Among women aged 18 to 21, ever OC use was significantly associated with decreased IGF-1 levels compared to never use (β = -57.2 ng/ml, 95% confidence interval (CI): -88.7, -25.8). Among women aged 31 to 40, past users who first used OC at 25 years of age or older (β = 43.8 ng/ml, 95% CI: 8.8, 78.8), in the last 15 years (β = 35.1 ng/ml, 95% CI: 9.3, 61.0) or after 1995 (β = 46.6 ng/ml, 95% CI: 13.4, 79.8) had significantly higher IGF-1 levels compared to never users.</p> <p>Conclusion</p> <p>This is the first study to highlight the long term effects of OC use after cessation on IGF-1 levels among premenopausal women, which previously were thought to be transitory. Future studies of past use and IGF-1 levels are required and must consider age/timing of use and type/generation of OC used. Additional studies are needed to confirm the potential mediation of IGF-1 levels in the links between OC use and health outcomes.</p

EPAC-Lung:Pooled analysis of circulating tumor cells in advanced non-small cell lung cancer

Background: We assessed the clinical validity of circulating tumor cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a European pooled analysis of individual patient data. This is the largest study of its kind and the first to examine between-centre heterogeneity of CTC identification in NSCLC.Methods: Nine European NSCLC CTC centers were asked to provide reported/unreported anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 - March 2017. We used Cox regression models, stratified by centre, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinico-pathological models using likelihood ratio (LR) statistics and c-indices.Results: Seven out of nine eligible centers provided data for 550 eligible patients, including 209 patients whose prognostic information was previously unpublished. CTC counts of ≥ 2 and ≥5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: HR 1.72, p &lt; 0·001; ≥5 CTCs: HR 2.21, p &lt; 0·001) and overall survival (≥2 CTCs: HR 2·18, p &lt; 0·001; ≥5 CTCs: HR 2·75, p &lt; 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinico-pathological models (log-transformed CTCs p &lt; 0·0001; ≥2 CTCs p &lt; 0·0001; ≥5 CTCs p &lt; 0·0001), while more moderate improvements were observed with the use of c-index models. There was minor evidence of between-center heterogeneity in the effect on PFS, but not OS.No difference in CTC profile was observed between key NSCLC molecular subsets such as EGFR, ALK, and KRAS.Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC. CTC count improves prognostication when added to full clinico-pathological predictive models. ≥2 CTCs is an appropriate cutoff to move towards establishing clinical utility