Novel cell models to study breast tumour microenvironment and disease progression

Breast cancer is the most prevalent and deadly in woman. ER+ breast cancer represents around two-thirds of all cases and has a favourable prognosis due to good response to endocrine therapy. However, these tumours present 25% of disease relapse due to drug resistance and metastatic behaviour. Tumour progression and acquired drug resistance are modulated by the interactions between tumour cells and the surrounding microenvironment. Most models employed to address these mechanisms fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. (...

Prática desportiva de adolescentes em acolhimento residencial : percepções, significados e motivações

Este estudo teve como principal objectivo analisar as percepções, significados e motivações que adolescentes em acolhimento residencial manifestam sobre a sua prática desportiva. Para o desenvolvimento desta investigação, foram entrevistados 25 adolescentes de três casas de acolhimento do distrito do Porto, com idades compreendidas entre os 12 e os 19 anos. Foi utilizado um guião semi-estruturado e realizada uma análise de conteúdo com recurso ao NVivo. Os resultados apontam para claros benefícios da prática de desporto ao nível do bem-estar dos adolescentes, influenciando-os de forma positiva no seu quotidiano. Os adolescentes identificam aprendizagens para a vida, tais como a persistência, a resiliência e o valor do esforço. Os dados sugerem a importância de se favorecer a prática desportiva de adolescentes em acolhimento residencial, intencionalizando estes momentos através da promoção de oportunidades de reflexão potenciadoras do desenvolvimento das crianças e jovens.The main objective of this study was to analyze the perceptions, meanings and motivations that teenagers in host institutions show about their sports practice. For the development of this research, 25 teenagers aged between 12 and 19 years, from three host institutions in Porto area, were questioned. A semi-structured script was used and a qualitative content analysis was performed through NVivo software. The obtained results point to clear benefits of practicing sport in terms of well-being, influencing teenagers in a positive way in their daily lives. Adolescents identify lifelong learning, such as persistence, resilience, and the value of effort. The obtained data suggest the importance of favoring the sports practice of teenagers in host institutions, by making these moments available through the promotion of reflection opportunities advantageous to the development of children and young people

Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

<p>Abstract</p> <p>Background</p> <p>Antimicrobial resistance mediated by efflux systems is still poorly characterized in <it>Staphylococcus aureus</it>, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 <it>S. aureus </it>isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones.</p> <p>Results</p> <p>Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of <it>grlA </it>and <it>gyrA </it>genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that <it>S. aureus </it>clinical isolates may be primed to efflux antimicrobial compounds.</p> <p>Conclusions</p> <p>The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in <it>S. aureus</it>, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential role played by efflux systems in the development of resistance to fluoroquinolones in clinical isolates of <it>S. aureus</it>.</p

Genome Characterization and Spaciotemporal Dispersal Analysis of Bagaza Virus Detected in Portugal, 2021

Funding Information: This work received financial support from the Global Health and Tropical Medicine Center (which is funded through Fundação para a Ciência e a Tecnologia (FCT) contract UID/Multi/04413/2013). This research was also funded by FCT, Project UIDB/00276/2020 and LA/P/0059/2020-AL4AnimalS, and by the Interdisciplinary Research Center on Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon (Portugal). Finally, this research was also partially funded by the Interdisciplinary Research Center on Animal Health (Project CIISA-INOV 4/2021), Faculty of Veterinary Medicine, University of Lisbon (CIISA, FMV-UL) (Portugal). Publisher Copyright: © 2023 by the authors.In September 2021, Bagaza virus (BAGV), a member of the Ntaya group from the Flavivirus genus, was detected for the first time in Portugal, in the heart and the brain of a red-legged partridge found dead in a hunting ground in Serpa (Alentejo region; southern Portugal). Here we report the genomic characterization of the full-length sequence of the BAGV detected (BAGV/PT/2021), including phylogenetic reconstructions and spaciotemporal analyses. Phylogenies inferred from nucleotide sequence alignments, complemented with the analysis of amino acid alignments, indicated that the BAGV strain from Portugal is closely related to BAGV strains previously detected in Spain, suggesting a common ancestor that seems to have arrived in the Iberia Peninsula in the late 1990s to early 2000s. In addition, our findings support previous observations that BAGV and Israel turkey meningoencephalitis virus (ITV) belong to the same viral species.publishersversionpublishe

Trends in the diagnostic delay and pathway for amyotrophic lateral sclerosis patients across different countries

BackgroundAmyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with a median survival of 2–5 years. An early diagnosis is essential for providing ALS patients the finest management possible. Studies from different countries report a similar median diagnostic delay of around 12 months, which is still far from desirable. We analyzed the diagnostic pathway in different countries in order to identify the major challenges.MethodsWe studied a cohort of 1,405 ALS patients from five different centers, in four different countries (Turkey, Germany, Poland, and Portugal), which collaborated in a common database. Demographic, disease and sociocultural factors were collected. Time from first symptom onset to first medical evaluation and to diagnosis, the specialist assessment and investigations requested were analyzed. Factors contributing to diagnostic delay were evaluated by multivariate linear regression.ResultsThe median diagnostic delay from first symptom onset was 11 months and was similar between centers. Major differences were seen in the time from symptom onset to first medical evaluation. An earlier first medical evaluation was associated with a longer time to diagnosis, highlighting that ALS diagnosis is not straightforward in the early stages of the disease. The odds for ALS diagnosis were superior when evaluated by a neurologist and increased over time. Electromyography was decisive in establishing the diagnosis.ConclusionsWe suggest that a specific diagnostic test for ALS—a specific biomarker—will be needed to achieve early diagnosis. Early referral to a neurologist and to electromyography is important for early ALS diagnosis

Dopplerfluxometria das artérias intra-renais em cutias (Dasyprocta prymnolopha, Wagler 1831)

A técnica de dopplerfluxometria é importante para aferir a hemodinâmica renal, auxiliando no diagnóstico e prognóstico de problemas renais, todavia estudos com animais silvestres ainda são escassos. Assim sendo, é de extrema importância o desenvolvimento de estudos com o intuito de estabelecer valores de referências normais nas diferentes espécies, uma vez que esses dados servirão como base para a compreensão da anatomia e fisiologia, bem como, diagnóstico de doenças na clínica veterinária. Neste sentido, este trabalho teve como objetivo obter dados dos aspectos ultrassonográficos renais normais em cutias (Dasyprocta prymnolopha, Wagler 1831). Para avaliação da morfometria ultrassonográfica utilizou-se oito cutias, nas quais foram avaliados o comprimento e largura dos rins direito e esquerdo. Para avaliação da dopplerfluxometria foram utilizadas 11 cutias, sendo analisadas as velocidades do pico sistólico máximo (VPS) e diastólico final (VDF) do fluxo sanguíneo (cm/s) e do índice de resistividade (IR) das artérias arqueadas dos rins direito e esquerdo. Os valores médios do comprimento e largura em centímetros do rim direito e esquerdo variaram entre 3,05 ± 0,13 a 1,84 ± 0,12 e 3,04 ± 0,19 a 1,91 ± 0,10, respectivamente. O valor médio observado para o índice de resistividade na artéria arqueada dos rins direito e esquerdo foram 0,41 ± 0,06 e 0,39 ± 0,05 cm/s, respectivamente. O índice de resistividade foi inferior aos observados em outras espécies de animais domésticos e até mesmo de humanos

Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013–2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain–Barré syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV

Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis

Background: Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis. Methods: Expressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry. Results: All proteins were overexpressed in primary CRC, lymph node and hepatic metastasis, when compared with non-neoplastic tissue, with exception of MCT1 in lymph node and hepatic metastasis. MCT1 and MCT4 expressions were associated with CD147 and GLUT1 in primary CRC. These markers were associated with clinical pathological features, reflecting the putative role of these metabolism-related proteins in the CRC setting. Conclusion: These findings provide additional evidence for the pivotal role of MCTs in CRC maintenance and progression, and support the use of MCTs as biomarkers and potential therapeutic targets in primary and metastatic CRC.This work was supported by the Fundação para a Ciência e a Tecnologia (FCT) grant ref. PTDC/SAU-FCF/104347/2008, under the scope of ‘Programa Operacional Temático Factores de Competitividade’ (COMPETE) of ‘Quadro Comunitário de Apoio III’ and co-financed by the Fundo Europeu De Desenvolvimento Regional (FEDER). Ricardo Amorim was recipient of the fellowship SFRH/BD/98002/2013, from Fundação para a Ciência e a Tecnologia (FCT Portugal).info:eu-repo/semantics/publishedVersio