GNAQ and BRAF mutations show differential activation of the mTOR pathway in human transformed cells

Somatic mutations in GNAQ gene were described as being the main oncogenic activation in uveal melanomas, whereas mutations in BRAF gene have been described as a key genetic alteration that contributes to skin melanoma development. We have previously reported differential activation of the MAPK and AKT/mTOR signalling pathways in uveal and skin melanomas harbouring, respectively, GNAQ and BRAF mutations. The aim of this work was to compare the functional effect of GNAQ and BRAF mutations in mTOR and MAPK pathway activation, cell proliferation and apoptosis. In this work, we performed transient transfection of HEK293 cells with BRAFWT, BRAFV 600E, GNAQWT, GNAQQ209P and GNAQQ209L vectors. We treated melanoma cell lines displaying different BRAF and GNAQ mutational status with the mTOR inhibitor RAD001 and with the MEK1/2 inhibitor U0126 and evaluated the effects in the growth of the cell lines and in mTOR and MAPK pathway effectors expression. At variance with the significant increase in the level of pmTOR Ser2448 and pS6 Ser235/236 proteins observed in cells transfected with BRAF vectors, no significant alteration in mTOR pathway effectors was observed in cells transfected with the three GNAQ expressing vectors. Also, GNAQ overexpression enhances Stat3 activation, which might mediate GNAQ oncogenic effects. None of the vectors led to significant differences in proliferation or apoptosis in the transfected cell lines. Cell lines harbouring a BRAF mutation were more sensitive to RAD001 treatment. U0126 leads to the reduction of MAPK and mTOR pathways activation in all cell lines tested. Our results indicate that GNAQ and BRAF activation drive distinct intracellular signalling pathways that may be useful for therapeutic decisions in human melanomas

Dealing with Multisource Information for Estuarine Flood Risk Appraisal in Two Western European Coastal Areas

Estuaries are usually affected by compound flooding triggers that cause diverse territorial damages. While fluvial flood risk assessment frameworks are well established in the literature, integrated management instruments that deal with estuarine flood risk remain incomplete and often lacking. This research presents a methodology to extract relevant information from multiple sources post-event and a database building process that is applied to two contrasting estuaries (the Tagus River estuary in Portugal, and the Shannon River estuary in Ireland) in the Western European coastal area. Overall, a total of 274 documents were analyzed and the information was stored in two databases. Multiple correspondence analysis was applied to extract the most informative and relevant estuarine flood indicators. An integrated estuarine flood risk assessment framework is presented and discussed based on the extracted indicators. The framework is driven by two distinct dimensions (oceanic and hydrographic) and revealed the transversal position of triggers of estuarine floods, reflecting the compounding effects usually present in these areas. The results also highlight two levels of flood risk mostly based on damage typology.info:eu-repo/semantics/acceptedVersio

Automatic 3D pulmonary nodule detection in CT images: a survey

This work presents a systematic review of techniques for the 3D automatic detection of pulmonary nodules in computerized-tomography (CT) images. Its main goals are to analyze the latest technology being used for the development of computational diagnostic tools to assist in the acquisition, storage and, mainly, processing and analysis of the biomedical data. Also, this work identifies the progress made, so far, evaluates the challenges to be overcome and provides an analysis of future prospects. As far as the authors know, this is the first time that a review is devoted exclusively to automated 3D techniques for the detection of pulmonary nodules from lung CT images, which makes this work of noteworthy value. The research covered the published works in the Web of Science, PubMed, Science Direct and IEEEXplore up to December 2014. Each work found that referred to automated 3D segmentation of the lungs was individually analyzed to identify its objective, methodology and results. Based on the analysis of the selected works, several studies were seen to be useful for the construction of medical diagnostic aid tools. However, there are certain aspects that still require attention such as increasing algorithm sensitivity, reducing the number of false positives, improving and optimizing the algorithm detection of different kinds of nodules with different sizes and shapes and, finally, the ability to integrate with the Electronic Medical Record Systems and Picture Archiving and Communication Systems. Based on this analysis, we can say that further research is needed to develop current techniques and that new algorithms are needed to overcome the identified drawbacks

Fish resource exploitation in the southern Atlantic coast of the Iberian Peninsula: A view from the traceological analysis of flaked stone tools (sixth-fourth mill. cal BCE)

In this paper, we provide new data on fish resource exploitation during the Mesolithic and Neolithic period on the Atlantic coast of the Iberian Peninsula. Evidence from four different sites is presented: Vale Marim I (end of the seventh/beginning of the sixth millennium cal BCE) and Vale Pincel I (2nd and 3rd quarters of the sixth millennium cal BCE), both located on the southwestern Portuguese coast, and La Esparragosa and SET Parralejos (fourth-third millennia cal BCE), both located on the southern Spanish coast. The analysis of the lithic assemblages by means of use-wear analysis provided evidence of fish-processing activities. The analysis of the archaeological tools has been based on a renewed experimental framework for fish-related use-wear traces. Despite data being still scarce and fragmentary, this study points out the necessity of a more integrating approach, including traceological analysis in the framework of a broader research on prehistoric fishing.info:eu-repo/semantics/acceptedVersio

Portuguese validation of the children's eating attitudes test

CONTEXTO: O Teste de Atitudes Alimentares é o instrumento mais utilizado para avaliar distúrbios alimentares em adultos e adolescentes em uma variedade de culturas e amostras. OBJETIVO: O objetivo deste estudo foi avaliar as propriedades psicométricas da versão portuguesa da Escala de Atitudes Alimentares para Crianças (ChEAT). MÉ;TODO: Novecentos e cinquenta e seis alunos do ensino secundário (565 moças e 391 moços) responderam ao ChEAT. O cálculo da fidelidade teste-reteste foi feito por meio das respostas de 206 participantes da amostra total que voltaram a responder ao questionário após quatro a seis semanas. As análises psicométricas foram realizadas para o total da amostra e para ambos os sexos separadamente. RESULTADOS: A consistência interna e a fidelidade teste-reteste foram satisfatórias. A análise fatorial em componentes na amostra total resultou em quatro fatores que explicam 42,35% da variância total. A composição dos fatores foi semelhante na amostra total e em ambos os sexos. Os fatores denominaram-se: F1 "Medo de Engordar"; F2 "Comportamentos Restritivos e Purgativos"; F3 "Preocupação com a Comida" e F4 "Pressão Social para Comer". A validade concorrente foi explorada com a Escala de Silhuetas Corporais (CDFRS) e foi elevada. CONCLUSÃO: A versão portuguesa do ChEAT é um instrumento útil e válido para a avaliação de atitudes e comportamentos alimentares em adolescentes portugueses.BACKGROUND: The Eating Attitudes Test (EAT) is the most widely used instrument for evaluating eating disorders in adults and adolescents in a variety of cultures and samples. OBJECTIVE: The aim of this study was to analyse the psychometric properties of the Portuguese version of the Children's Eating Attitudes Test (ChEAT). METHOD: Nine hundred and fifty-six Portuguese secondary students (565 girls and 391 boys) answered the ChEAT. The test-retest reliability was obtained with data from 206 participants from the total sample who re-answered the questionnaire after 4-6 weeks. Psychometric analyses were carried out for the total sample and separately for girls and boys. RESULTS: Internal consistency and test-retest reliability were satisfactory. Principal components factorial analysis yielded four factors in the total sample, accounting for 42.35% of the total variance. Factor structure was similar in the total sample and in both genders. Factors were labelled: F1 "Fear of Getting Fat", F2 "Restrictive and Purgative Behaviours", F3 "Food Preoccupation" and F4 "Social Pressure to Eat". The concurrent validity, explored using the Contour Drawing Figure Rating Scale (CDRS) was high. DISCUSSION: The Portuguese version of the ChEAT is a valid and useful instrument for the evaluation of abnormal eating attitudes and behaviours among Portuguese adolescents

TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas

Funding: This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/ 2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology.Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives:Weaimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P< .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P=.001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P=.001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01-53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36-415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.publishersversionpublishe

Left ventricular diastolic function in morbidly obese patients in the preoperative for bariatric surgery

FUNDAMENTO: Obesidade é uma doença crônica, multifatorial, associada a aumento do risco cardiovascular, especialmente a insuficiência cardíaca diastólica. OBJETIVO: Avaliar a função diastólica do ventrículo esquerdo em obesos graves em pré-operatório para cirurgia bariátrica, relacionando com os fatores de risco cardiovascular e a estrutura cardíaca. MÉTODOS: Trata-se de um estudo transversal, com 132 pacientes candidatos a cirurgia bariátrica, submetidos a avaliação ecocardiográfica transtorácica e dos fatores de risco cardiovascular, sendo: 97 mulheres (73,5%), idade média de 38,5 ± 10,5 anos e IMC de 43,7 ± 7,2 Kg/m². Foram divididos em três grupos: 61 com função diastólica normal, 24 com disfunção diastólica leve e 47 com disfunção diastólica moderada/grave, dos quais 41 com disfunção diastólica moderada (padrão pseudonormal) e seis com disfunção diastólica grave (padrão restritivo). RESULTADOS: Hipertensão arterial sistêmica, idade e gênero foram diferentes nos grupos com disfunção diastólica. Os grupos com disfunção tiveram maior diâmetro do átrio esquerdo, do ventrículo esquerdo, volume do átrio esquerdo em quatro e duas câmaras, índice de volume atrial esquerdo e índice de massa do ventrículo esquerdo corrigido para a superfície corpórea e para altura. CONCLUSÃO: A elevada frequência de disfunção diastólica do ventrículo esquerdo na fase pré-clínica em obesos graves justifica a necessidade de uma avaliação ecocardiográfica criteriosa, com o objetivo de identificar indivíduos de maior risco, para que medidas de intervenção precoce sejam adotadas. _________________________________________________________________________________________ ABSTRACT: BACKGROUND: Obesity is a chronic and multifactorial disease, associated with increased cardiovascular risk, especially diastolic heart failure. OBJECTIVE: To evaluate left ventricular diastolic function in morbidly obese patients in the pre-operative for bariatric surgery, correlating it with cardiovascular risk factors and heart structure. METHODS: This is a cross-sectional study with 132 patients eligible for bariatric surgery submitted to transthoracic echocardiography assessment and of cardiovascular risk factors, as follows: 97 women (73.5%), mean age 38.5 ± 10.5 years and BMI of 43.7 ± 7.2 kg / m². Patients were divided into three groups: 61 with normal diastolic function, 24 with mild diastolic dysfunction and 47 with moderate/severe diastolic dysfunction, of which 41 with moderate diastolic dysfunction (pseudonormal pattern) and six with severe diastolic dysfunction (restrictive pattern). RESULTS: Hypertension, age and gender were different in the groups with diastolic dysfunction. Groups with dysfunction had higher left atrial diameter, left ventricular diameter, left atrial volume in four and two chambers, left atrial volume index and left ventricular mass index corrected for body surface area and height. CONCLUSION: The high frequency of left ventricular diastolic dysfunction in the preclinical phase in morbidly obese patients justifies the need for careful echocardiographic assessment, aiming at identifying individuals at higher risk, so that early intervention measures can be carried out

TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.We acknowledge GENZYME for funding our work through a research project. This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology

estudos artísticos

Como é característica fundadora do projeto CSO – criadores sobre outras obras – os artistas são aqui convidados a comunicar o seu conhecimento sobre outros artistas, dentro de um descentramento que toma os idiomas ibéricos como uma plataforma territorial de emergência, e de resistência, também. É uma área cultural periférica, alternativa, que se afirma em crescente grandeza. Dentro deste dispositivo comunicativo, a revista Croma delimita mais ainda o seu tema, nos artistas que de algum modo fazem incorporar a implicação social, a interação e a criação e formação de novos públicos como um dos componentes estruturantes da sua obra. Surgem na Croma obras intervenientes, que provocam, e que convocam, que estabelecem pontes, ou que as ameaçam. São obras em que a componente relacional (N. Bourriaud) ou formativa e integradora (P. Freire) assumem uma atualidade constante e renovada. Os artigos reunidos neste quinto número da Revista Croma propõem, no seu conjunto uma intenção de proximidade, de confronto com realidades, de inconformismo, de procura e de questionamento identitário. Dos seus múltiplos países e das suas diversificadas abordagens a variadas técnicas, os vinte e cinco artigos aqui apresentados complementam o poder do desassossego e da inquietação poética: os artistas falam connosco, através de outros artistas, que os souberam ver e ouvir.info:eu-repo/semantics/publishedVersio