Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease

Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease

EurOP2E – the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers

Purpose Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. Methods CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. Results Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. Conclusion Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system

A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants

Background: defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene MUTYH are responsible for MUTYH-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested MUTYH mono-allelic variants to be low penetrance risk alleles. We report a large collaborative meta-analysis to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic MUTYH variants and investigate age and sex influence on risk. Methods: MUTYH genotype data were included from 20 565 cases and 15 524 controls. Three logistic regression models were tested: a crude model; adjusted for age and sex; adjusted for age, sex and study. Results: all three models produced very similar results. MUTYH bi-allelic carriers demonstrated a 28-fold increase in risk (95% confidence interval (CI): 6.95-115). Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C (odds ratio (OR)=1.34; 95% CI: 1.00-1.80). A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02-23.2; OR=6.47, 95% CI: 2.33-18.0; OR=3.35, 95% CI: 1.14-9.89) and marginal mono-allelic effect for variants MUTYH (OR=1.16, 95% CI: 1.00-1.34) and Y179C alone (OR=1.34, 95% CI: 1.01-1.77). Conclusions: overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic MUTYH carriers

Análise da atividade e gasto fisiológico dos catadores de resíduos sólidos: a percepção da terapia ocupacional

The world’s transformation in the market has been causing changes in the working class. As those changes have come, the market calls for a high capacity from the workers. Due to that, the unemployment rate has increased and induced a new type of class worker: the Recyclable Material Collectors. In this job, the role of the collector is to return the materials to their commodity chain, and to accomplish this, two methods of collecting are used: one with a truck and the other with a manual collector car. This is one type of occupation which has an extenuating work time, where the worker is exposed to a high ergonomic risk. This study, which was labored from a quantitative and qualitative approach to exploratory method and field research, is intended to compare which collecting technique can be less weariness to the worker. To the purpose of comparison of the physiological work weight, the participants used the Polar FT7 frequency counter, which generated, in graphic form, the performance of the collector in both methods. According to the values presented, was concluded that three of the four participants had a higher physiological weariness by using the manual car collecting approach, concluding that this method is the one that brings most effort to the worker. Considering the results obtained in this research, it was possible to observe that the use of the manual car causes a higher damage to the health of the recyclable material collector.A transformação no mundo do trabalho tem causado mudanças no perfil da classe trabalhadora. Cada vez mais, o mercado de trabalho requer exigências e, como decorrência disso, a taxa de desemprego aumentou e fez surgir uma nova profissão, a de Catadores de Materiais Recicláveis. A função do catador é a de devolver os materiais à sua cadeia produtiva e, para isso, existem dois métodos de coleta: com o caminhão e com o carro manual de coleta. Essa é uma profissão que possui jornadas de trabalho extenuantes, nas quais o trabalhador está exposto a riscos ergonômicos. Esse estudo foi elaborado a partir de uma abordagem quantitativa e qualitativa de método explorátorio e pesquisa de campo; pretende comparar qual método de coleta causa menos desgaste ao trabalhador. Para fins de comparação da carga fisiológica do trabalho, os participantes utilizaram o frequencímetro Polar FT7 que gerou, em forma de gráfico, o desempenho do catador em ambos os métodos de coleta. De acordo com os valores expostos, avaliou-se que, dos 4 participantes, 3 apresentaram um maior desgaste fisiológico no método de coleta com o carro manual, sendo esta a forma pela qual o trabalhador realiza mais esforços. Considerando os resultados obtidos nessa pesquisa, foi possível observar que o uso do carro manual de coleta causa um maior prejuízo à saúde do catador de materiais recicláveis