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.

Nanotechnology and antioxidant therapy: An emerging approach for neurodegenerative diseases

The efficacy, cellular uptake and specific transport of dietary antioxidants to target organs, tissues and cells remains the most important setback for their application in the treatment of oxidative-stress related disorders and in particular in neurodegenerative diseases, as brain targeting remains a still unsolved challenge. Nanotechnology based delivery systems can be a solution for the above mentioned problems, specifically in the case of targeting dietary antioxidants with neuroprotective activity. Nanotechnology-based delivery systems can protect antioxidants from degradation, improve their physicochemical drug-like properties and in turn their bioavailability. The impact of nanomedicine in the improvement of the performance of dietary antioxidants, as protective agents in oxidative- stress events, specifically through the use of drug delivery systems, is highlighted in this review as well as the type of nanomaterials regularly used for drug delivery purposes. From the data one can conclude that the research combining (dietary) antioxidants and nanotechnology, namely as a therapeutic solution for neurodegenerative diseases, is still in a very early stage. So, a huge research area remains to be explored that hopefully will yield new and effective neuroprotective therapeutic agents in a foreseeable future.

A comparison between thin film solar cells made from co-evaporated CuIn1-xGaxSe2using a one-stage process versus a three-stage process

Until this day, the most efficient Cu(In,Ga)Se2 thin film solar cells have been prepared using a rather complex growth process often referred to as three-stage or multistage. This family of processes is mainly characterized by a first step deposited with only In, Ga and Se flux to form a first layer. Cu is added in a second step until the film becomes slightly Cu-rich, where-after the film is converted to its final Cu-poor composition by a third stage, again with no or very little addition of Cu. In this paper, a comparison between solar cells prepared with the three-stage process and a one-stage/in-line process with the same composition, thickness, and solar cell stack is made. The one-stage process is easier to be used in an industrial scale and do not have Cu-rich transitions. The samples were analyzed using glow discharge optical emission spectroscopy, scanning electron microscopy, X-ray diffraction, current–voltage-temperature, capacitance-voltage, external quantum efficiency, transmission/reflection, and photoluminescence. It was concluded that in spite of differences in the texturing, morphology and Ga gradient, the electrical performance of the two types of samples is quite similar as demonstrated by the similar J–V behavior, quantum spectral response, and the estimated recombination losses.

Writing and living on the stage of history

This article studies the intercultural trajectory of a Portuguese female aristocrat of the eighteenth to nineteenth centuries. Her trajectory of intercultural transition from a Portuguese provincial lady into an independent owner of a sugar mill in tropical Bahia is documented through family letters, which provide a polyphonic representation of a movement of personal, family, and social transculturation over almost two decades. Maria Bárbara began her journey between cultures as a simple spectator-reader, progressively becoming a commentator-actor-protagonist-author in society, in politics, and in history. These letters function as a translation that is sometimes consecutive, other times simultaneous, of the events lived and witnessed. This concept of intercultural translation is based on the theories of Boaventura de Sousa Santos (2006, 2008), who argues that cultural differences imply that any comparison has to be made using procedures of proportion and correspondence which, taken as a whole, constitute the work of translation itself. These procedures construct approximations of the known to the unknown, of the strange to the familiar, of the ‘other’ to the ‘self’, categories which are always unstable. Likewise, this essay explores the unstable contexts of its object of study, with the purpose of understanding different rationalities and worldviews.

Relatório de estágio em Ensino do 1.º Ciclo do Ensino Básico

Relatório EPE - Relatório de estágio em Educação Pré-Escolar: O presente relatório foi realizado no âmbito da unidade curricular Prática Pedagógica Supervisionada, inserida no Mestrado em Educação Pré-Escolar e Ensino do 1.º Ciclo do Ensino Básico, da Escola Superior de Educação do Porto, durante o ano letivo 2013/2014, atribuindo qualificação profissional no contexto de pré-escolar. Este documento pretende descrever e analisar o percurso formativo desenvolvido pela mestranda ao longo da sua prática pedagógica supervisionada, numa perspetiva reflexiva sobre a construção dos saberes profissionais para a Educação. Este percurso formativo comprometeu uma atitude investigativa, bem como a mobilização de saberes científicos e legais por forma a articular as vertentes de teoria e prática, perspetivando uma construção integrada dos saberes. A prática pedagógica foi sustentada numa perspetiva construtivista, atribuindo um papel ativo à criança na construção das suas aprendizagens. Esta baseou-se num trabalho de equipa cooperativo, o qual se concretiza através do debate e da partilha de ideias, entre os vários intervenientes da ação, como meio para a transformação da realidade educativa. Ao longo da prática foi, ainda, atribuído um papel fundamental à observação do contexto, sendo esta essencial para a compreensão e conhecimento pleno da criança. Em suma, todo o percurso formativo no qual está englobado a prática pedagógica, levou a uma problematização das questões emergentes da prática, desenvolvendo uma atitude indagadora e reflexiva. Apesar da significante contribuição para a aquisição de competências pessoais e profissionais, o percurso formativo deve ser assumido como uma construção contínua, fundamentado num princípio da aprendizagem ao longo da vida.