Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success. To improve clinical outcomes, translational models predictive of drug response are needed. We describe a simple method for the fast establishment of CRC patient-derived explant (CRC-PDE) cultures from different carcinogenesis pathways, employing agitation-based platforms. A total of 26 CRC-PDE were established and a subset was evaluated for viability (n = 23), morphology and genetic key alterations (n = 21). CRC-PDE retained partial tumor glandular architecture and microenvironment features were partially lost over 4 weeks of culture. Key proteins (p53 and Mismatch repair) and oncogenic driver mutations of the original tumours were sustained throughout the culture. Drug challenge (n = 5) revealed differential drug response from distinct CRC-PDE cases. These findings suggest an adequate representation of the original tumour and highlight the importance of detailed model characterisation. The preservation of key aspects of the CRC microenvironment and genetics supports CRC-PDE potential applicability in pre- and co-clinical settings, as long as temporal dynamics are considered.

Rare and unknown canine systemic mastocytosis: clinical and laboratory features of an aberrant c-Kit mutation neoplasia / A rara e desconhecida mastocitose sistêmica canina: características clínicas e laboratoriais de uma neoplasia aberrante na mutação c-Kit

Systemic mastocytosis (SM) pathology is extremely rare in canine practice, with insufficient reported data. The knowledge of the clinical behavior of this pathology is scarce. In human medicine, SM has been widely investigated, being defined as a rare hematopoietic disorder by the World Health Organization (2016), within the type of myeloproliferative neoplasms. Herein, we describe a systemic mastocytosis case in a Portuguese Serra-da-Estrela dog, where a cutaneous grade III/high-grade MCT was also diagnosed. The clinical decline of the animal and owner's insistence throughout anamnesis that the dog was markedly different after the cytologic exam performed in another clinic, along with both severe eosinophilia and hepatomegaly, led to the clinical suspicion of SM. The animal passed away 7 days later. Post-morteminvestigation confirmed SM pathology, and a deletion of 15 base pairs change on c-Kit gene exon 11 was identified. Contemplating the low number of cases described in the literature, this publication aims to disclose clinical and laboratory features of rare and poorly described canine SM, taking into consideration human outcomes described in the literature.(AU)

A patologia da mastocitose sistêmica (SM) é extremamente rara na prática clínica canina, com escassos casos descritos na literatura científica. O conhecimento do comportamento clínico desta patologia é mínimo. Na medicina humana, a SM tem sido amplamente investigada, sendo definida como uma doença hematopoiética rara pela Organização Mundial da Saúde (2016), dentro do tipo de neoplasias mieloproliferativas. Descrevemos aqui um caso de mastocitose sistêmica num cão Serra-da-Estrela português, diagnosticado também com um mastocitoma cutâneo grau III / alto grau. O declínio clínico do animal e a insistência do proprietário durante a anamnese de que o cão estava marcadamente diferente após o exame citológico realizado em outra clínica, juntamente com eosinofilia e hepatomegalia graves, levantaram a suspeita clínica de SM. O animal faleceu 7 dias depois. A investigação post-mortem confirmou a patologia SM, e o estudo molecular revelou uma deleção de 15 pares de bases no exon 11 do gene c-Kit. Contemplando o baixo número de casos descritos na literatura, o objetivo desta publicação é divulgar características clínicas e laboratoriais de SM canina, levando em consideração informações clínicas descritas em humanos.(AU)

Influence of weather variables on physical activity assessed by accelerometry across age and gender groups / Influência das variáveis do clima na atividade física avaliada por acelerometria em homens e mulheres de diferentes faixas etárias

The purpose of this research was to study the effects of weather on physical activity and compliance to minimum physical activity recommendations. Participants included 257 women and 178 men. Time spent in physical activity, average daily steps, and weather variables were gathered and analysed to explore the influence of weather on PA and compliance with the PA recommendations. In result, environmental factors may have a weak influence in an individual will to engage in PA, and individuals highly committed to an active lifestyle (based on the number of steps taken per day) did not seem to be influenced by any of the weather variables. To conclude, considering the known barriers to an active lifestyle, this information is markedly important since engaging in physical activity on a day-to-day basis may be of extreme relevance to the maintenance of a healthy status, especially in the elderly.

O objetivo deste estudo foi analisar os efeitos do clima na atividade física e no cumprimento das recomendações para a atividade física, numa amostra constituída por 257 mulheres e 178 homens. O tempo despendido em atividade física, média de passos diários, e as variáveis do clima, foram recolhidas e analisadas no sentido de explorar a influência do clima na atividade física e no cumprimento das recomendações para a atividade física. Os resultados indicam que os fatores do clima têm uma fraca influência na vontade de um indivíduo se envolver na atividade física, e que indivíduos altamente comprometidos com um estilo de vida ativo (baseado no número de passos dados por dia) não parecem ser influenciados por qualquer das variáveis do clima. Considerando o conhecimento disponível associado às barreiras à manutenção de um estilo de vida ativo, esta informação parece ser relevante em trabalhos de intervenção, já que o envolvimento na atividade física diariamente é importante para a manutenção de um bom estado de saúde, especialmente nos idosos.

Does health promote economic growth? Portuguese case study: from dictatorship to full democracy.

This paper revisits the debate on health and economic growth (Deaton in J Econ Lit 51:113-158, 2003) focusing on the Portuguese case by testing the relationship between growth and health. We test Portuguese insights, using time series data from 1960 to 2005, taking into account different variables (life expectancy, labour, capital, infant mortality) and considering the years that included major events on the political scene, such as the dictatorship and a closed economy (1960-1974), a revolution (1974) and full democracy and an open economy (1975-2005), factors that influence major economic, cultural, social and politic indicators. Therefore the analysis is carried out adopting Lucas' (J Monet Econ 22(1):3-42, 1988) endogenous growth model that considers human capital as one factor of production, it adopts a VAR (vector autoregressive) model to test the causality between growth and health. Estimates based on the VAR seem to confirm that economic growth influences the health process, but health does not promote growth, during the period under study.