Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries

Background: Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome. Methods: Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed. Results: Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of >= 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson). Conclusions: The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.

Introducing education for sustainable development in the undergraduate laboratory: quantitative analysis of bioethanol fuel and its blends with gasoline by using solvatochromic dyes

The concept of Education for Sustainable Development, ESD, has been introduced in a period where chemistry education is undergoing a major change, both in emphasis and methods of teaching. Studying an everyday problem, with an important socio-economic impact in the laboratory is a part of this approach. Presently, the students in many countries go to school in vehicles that run, at least partially, on biofuels; it is high time to let them test these fuels. The use of renewable fuels is not new: since 1931 the gasoline sold in Brazil contains 20 to 25 vol-% of bioethanol; this composition is being continually monitored. With ESD in mind, we have employed a constructivist approach in an undergraduate course, where UV-vis spectroscopy has been employed for the determination of the composition of two fuel blends, namely, bioethanol/water, and bioethanol/gasoline. The activities started by giving a three-part quiz. The first and second ones introduced the students to historical and practical aspects of the theme (biofuels). In the third part, we asked them to develop a UV-vis experiment for the determination of the composition of fuel blends. They have tested two approaches: (i) use of a solvatochromic dye, followed by determination of fuel composition from plots of the empirical fuel polarity versus its composition; (ii) use of an ethanol-soluble dye, followed by determination of the blend composition from a Beer's law plot; the former proved to be much more convenient. Their evaluation of the experiment was highly positive, because of the relevance of the problem; the (constructivist) approach employed, and the bright colors that the solvatochromic dye acquire in these fuel blends. Thus ESD can be fruitfully employed in order to motivate the students; make the laboratory "fun", and teach them theory (solvation). The experiments reported here can also be given to undergraduate students whose major is not chemistry (engineering, pharmacy, biology, etc.). They are low-cost and safe to be introduced at high-school level.