48 resultados para Normally Complemented Subgroups


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Dissertação de mestrado em Engenharia e Gestão da Qualidade

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Dissertação de mestrado integrado em Materials Engineering

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Tese de Doutoramento em Ciências da Saúde

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Degree of Doctor of Philosophy of Structural/Civil Engineering

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Acetate is a short-chain fatty acid secreted by Propionibacteria from the human intestine, known to induce mitochondrial apoptotic death in colorectal cancer (CRC) cells. We previously established that acetate also induces lysosome membrane permeabilization in CRC cells, associated with release of the lysosomal protease cathepsin D (CatD), which has a well-established role in the mitochondrial apoptotic cascade. Unexpectedly, we showed that CatD has an antiapoptotic role in this process, as pepstatin A (a CatD inhibitor) increased acetate-induced apoptosis. These results mimicked our previous data in the yeast system showing that acetic acid activates a mitochondria-dependent apoptosis process associated with vacuolar membrane permeabilization and release of the vacuolar protease Pep4p, ortholog of mammalian CatD. Indeed, this protease was required for cell survival in a manner dependent on its catalytic activity and for efficient mitochondrial degradation independently of autophagy. In this study, we therefore assessed the role of CatD in acetate-induced mitochondrial alterations. We found that, similar to acetic acid in yeast, acetate-induced apoptosis is not associated with autophagy induction in CRC cells. Moreover, inhibition of CatD with small interfering RNA or pepstatin A enhanced apoptosis associated with higher mitochondrial dysfunction and increased mitochondrial mass. This effect seems to be specific, as inhibition of CatB and CatL with E-64d had no effect, nor were these proteases significantly released to the cytosol during acetate-induced apoptosis. Using yeast cells, we further show that the role of Pep4p in mitochondrial degradation depends on its protease activity and is complemented by CatD, indicating that this mechanism is conserved. In summary, the clues provided by the yeast model unveiled a novel CatD function in the degradation of damaged mitochondria when autophagy is impaired, which protects CRC cells from acetate-induced apoptosis. CatD inhibitors could therefore enhance acetate-mediated cancer cell death, presenting a novel strategy for prevention or therapy of CRC.

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Tese de Doutoramento em Engenharia Civil

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[Excerpt] A critical case from a Portuguese hospital reveals how the ultimate healthcare customer, the patient, is a complete system, not a jumble of parts. (...) The lean production philosophy has made inroads into service sectors, including medical care in the United Kingdom and the United States. Unfortunately, numerous medical organizations in those two countries and the rest of the world treat patients like they are made up of parts, not as a whole system. This leads to disjointed handoffs, bottlenecks in information flow that delay treatment, and sending the patient back and forth from department to department. The following case in Portugal shows how most of the world’s health systems still suffer from functional silos and how waste is all over the place. In this case, the missing links in communication between doctors, nurses, auxiliary staff, the patient and her family led to the patient’s death. Adopting lean healthcare with its proven tools would be a solution to many of the problems described. When a patient dies in a hospital, the family often is told that the doctors did everything they could. Normally, that is the case, as healthcare providers – doctors, nurses, auxiliary staff, therapists – do their best with the system they have.

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Background and aims: Small bowel capsule endoscopy (SBCE) allows mapping of small bowel inflammation in Crohn’s disease (CD). We aimed to assess the prognostic value of the severity of inflammatory lesions, quantified by the Lewis score (LS), in patients with isolated small bowel CD. Methods: A retrospective study was performed in which 53 patients with isolated small bowel CD were submitted to SBCE at the time of diagnosis. The Lewis score was calculated and patients had at least 12 months of follow-up after diagnosis. As adverse events we defined disease flare requiring systemic corticosteroid therapy, hospitalization and/or surgery during follow-up. We compared the incidence of adverse events in 2 patient subgroups, i.e. those with moderate or severe inflammatory activity (LS =790) and those with mild inflammatory activity (135 = LS < 790). Results: The LS was =790 in 22 patients (41.5%), while 58.5% presented with LS between 135 and 790. Patients with a higher LS were more frequently smokers (p = 0.01), males (p = 0017) and under immunosuppressive therapy (p = 0.004). In multivariate analysis, moderate to severe disease at SBCE was independently associated with corticosteroid therapy during follow-up, with a relative risk (RR) of 5 (p = 0.011; 95% confidence interval [CI] 1.5–17.8), and for hospitalization, with an RR of 13.7 (p = 0 .028; 95% CI 1.3–141.9). Conclusion: In patients with moderate to severe inflammatory activity there were higher prevalences of corticosteroid therapy demand and hospitalization during follow-up. Thus, stratifying the degree of small bowel inflammatory activity with SBCE and LS calculation at the time of diagnosis provided relevant prognostic value in patients with isolated small bowel CD.

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Dissertação de mestrado integrado em Engenharia Civil

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Relatório de estágio de mestrado em Ciências da Comunicação (área de especialização em Publicidade e Relações Públicas)

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Tese de Doutoramento em Ciências da Saúde

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Dissertação de mestrado em Direito dos Contratos e da Empresa

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Dissertação de mestrado em Direito dos Contratos e da Empresa

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Dissertação de mestrado em Técnicas de Caracterização e Análise Química