SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3

Prostate cancer (PCa) is one of the most incident cancers worldwide but clinical and pathological parameters have limited ability to discriminate between clinically significant and indolent PCa. Altered expression of histone methyltransferases and histone methylation patterns are involved in prostate carcinogenesis. SMYD3 transcript levels have prognostic value and discriminate among PCa with different clinical aggressiveness, so we decided to investigate its putative oncogenic role on PCa.We silenced SMYD3 and assess its impact through in vitro (cell viability, cell cycle, apoptosis, migration, invasion assays) and in vivo (tumor formation, angiogenesis). We evaluated SET domain's impact in PCa cells' phenotype. Histone marks deposition on SMYD3 putative target genes was assessed by ChIP analysis.Knockdown of SMYD3 attenuated malignant phenotype of LNCaP and PC3 cell lines. Deletions affecting the SET domain showed phenotypic impact similar to SMYD3 silencing, suggesting that tumorigenic effect is mediated through its histone methyltransferase activity. Moreover, CCND2 was identified as a putative target gene for SMYD3 transcriptional regulation, through trimethylation of H4K20.Our results support a proto-oncogenic role for SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic activity. Thus, SMYD3 overexpression is a potential biomarker for clinically aggressive disease and an attractive therapeutic target in PCa.

Desatando os nós da solidão com laços de afeto: Intervenção psicossocial em contexto domiciliário

Apesar de haver diferenças de indivíduo para indivíduo, todas as pessoas se encontram num processo de envelhecimento, que se pretende que seja ativo e saudável. Porém, à medida que nos aproximamos da velhice, e por inúmeros fatores, a probabilidade da pessoa se sentir só, de ter sentimentos como a solidão, de estar isolada ou socialmente excluída, aumenta. Este relatório surge de um projeto desenhado e desenvolvido com pessoas que se sentiam sozinhas, sendo pessoas idosas ou com deficiência, e que, por esse motivo, foram encaminhadas para apoio domiciliário. Pretendeu-se assim colmatar algumas das necessidades quotidianas dessas pessoas, sendo relevante entender se esse apoio contribuiu para melhorar a qualidade de vida, evitar ou diminuir os momentos e sentimentos de solidão, através da (re)ativação de redes de apoio. O projeto “Desatando os nós da solidão com laços de afeto” foi, na medida das suas possibilidades, desenhado e desenvolvido com os participantes. Este projeto ramificou-se em três subprojetos, correspondendo cada um, de forma mais específica, às necessidades e aos problemas que cada pessoa sentia, tentando contribuir para a melhoria da qualidade de vida, recorrendo às potencialidades de cada um e aos recursos existentes na comunidade. É um projeto que terá continuidade, pois envolveu voluntários e técnicos da instituição e pessoas das redes de apoio mais próximas dos participantes, mas que já proporcionou algumas mudanças, sendo esse um ponto de partida para alcançar a utopia orientadora do projeto.

Anti-Tumor Necrosis Factor Alpha-Induced Drug Eruptions: One Patient, More Than a Pattern

Background: Tumor necrosis factor alpha (TNFα) antagonists are effective in treating several immune-inflammatory diseases, including psoriasis and inflammatory bowel disease. The paradoxical and unpredictable induction of psoriasis and psoriasiform skin lesions is a recognized adverse event, although of unclear aetiology. However, histological analysis of these eruptions remains insufficient, yet suggesting that some might constitute a new pattern of adverse drug reaction, rather than true psoriasis. Case report: The authors report the case of a 43-year-old woman with severe recalcitrant Crohn disease who started treatment with infliximab. There was also a personal history of mild plaque psoriasis without clinical expression for the past eight years. She developed a heterogeneous cutaneous eruption of psoriasiform morphology with pustules and crusts after the third infliximab infusion. The histopathological diagnosis was of a Sweet-like dermatosis. The patient was successfully treated with cyclosporine in association with both topical corticosteroid and vitamin D3 analogue. Three weeks after switching to adalimumab a new psoriasiform eruption was observed, histologically compatible with a psoriasiform drug eruption. Despite this, and considering the beneficial effect on the inflammatory bowel disease, it was decided to maintain treatment with adalimumab and to treat through with topicals, with progressive control of skin disease. Discussion: Not much is known about the pathogenesis of psoriasiform eruptions induced by biological therapies, but genetic predisposition and Koebner phenomenon may contribute to it. Histopathology can add new facets to the comprehension of psoriasiform reactions. In fact, histopathologic patterns of such skin lesions appear to be varied, in a clear asymmetry with clinical findings. Conclusion: The sequential identification in the same patient of two clinical and histopathologic patterns of drug reaction to TNFα antagonists is rare. Additionally, to the authors’ knowledge, there is only one other description in literature of a TNFα antagonist-induced Sweet-like dermatosis, emphasizing the singularity of this case report.

A sustentabilidade do Alto Douro vinhateiro: realidade ou utopia? Contributo para a avaliação e melhoria da sustentabilidade da região

Tese apresentada para cumprimento dos requisitos necessários à obtenção do grau de Doutor em Geografia e Planeamento Territorial, especialidade em Geografia Humana

Familial Abdominal Aortic Aneurysm Is Associated With More Complications After Endovascular Aneurysm Repair

OBJECTIVE: A familial predisposition to abdominal aortic aneurysms (AAAs) is present in approximately one-fifth of patients. Nevertheless, the clinical implications of a positive family history are not known. We investigated the risk of aneurysm-related complications after endovascular aneurysm repair (EVAR) for patients with and without a positive family history of AAA. METHODS: Patients treated with EVAR for intact AAAs in the Erasmus University Medical Center between 2000 and 2012 were included in the study. Family history was obtained by written questionnaire. Familial AAA (fAAA) was defined as patients having at least one first-degree relative affected with aortic aneurysm. The remaining patients were considered sporadic AAA. Cardiovascular risk factors, aneurysm morphology (aneurysm neck, aneurysm sac, and iliac measurements), and follow-up were obtained prospectively. The primary end point was complications after EVAR, a composite of endoleaks, need for secondary interventions, aneurysm sac growth, acute limb ischemia, and postimplantation rupture. Secondary end points were specific components of the primary end point (presence of endoleak, need for secondary intervention, and aneurysm sac growth), aneurysm neck growth, and overall survival. Kaplan-Meier estimates for the primary end point were calculated and compared using log-rank (Mantel-Cox) test of equality. A Cox-regression model was used to calculate the independent risk of complications associated with fAAA. RESULTS: A total of 255 patients were included in the study (88.6% men; age 72 ± 7 years, median follow-up 3.3 years; interquartile range, 2.2-6.1). A total of 51 patients (20.0%) were classified as fAAA. Patients with fAAA were younger (69 vs 72 years; P = .015) and were less likely to have ever smoked (58.8% vs 73.5%; P = .039). Preoperative aneurysm morphology was similar in both groups. Patients with fAAA had significantly more complications after EVAR (35.3% vs 19.1%; P = .013), with a twofold increased risk (adjusted hazard ratio, 2.1; 95% confidence interval, 1.2-3.7). Secondary interventions (39.2% vs 20.1%; P = .004) and aneurysm sac growth (20.8% vs 9.5%; P = .030) were the most important elements accounting for the difference. Furthermore, a trend toward more type I endoleaks during follow-up was observed (15.6% vs 7.4%; P = .063) and no difference in overall survival. CONCLUSIONS: The current study shows that patients with a familial form of AAA develop more aneurysm-related complications after EVAR, despite similar AAA morphology at baseline. These findings suggest that patients with fAAA form a specific subpopulation and create awareness for a possible increase in the risk of complications after EVAR.

Attempts using cryotherapy to achieve more rapid healing in patients with cutaneous leishmaniasis due to L. braziliensis braziliensis

The use of cryotherapy as an adjunct to systemic antimonial therapy (Clucantime) was studied in 17 patients with a total of23 skin lesions of leishmaniasis in an area where L. braziliensis braziliensis is the species in circulation. Cryotherapy did not speed healing and has been discarded as an auxiliary therapeutic measure in our practice. However this technique may be suitable for species o/Leishmania causing more limited superficial lesions in man without the danger of metastasis.

Corte, poder e utopia: O Relox de Príncipes (1529) de Fr. Antonio de Guevara e a sua fortuna na Europa do século XVI

Em Valladolid era publicado, em 1529, o Libro llamado Relox de Príncipes, da autoria de fr. Antonio de Guevara, iniciando-se “[...] la más fantástica carrera y reputación literaria del siglo XVI, tanto dentro como fuera de España [...]” (Márquez Villanueva e Redondo 173). A história do Relox de Príncipes encontra-se intimamente ligada à edição, cerca de um ano antes, em Sevilha, nos prelos de Jacobo Cromberger, sem nome de autor, do Libro Áureo de Marco Aurelio, também da autoria de Guevara. Com efeito, a parte mais importante desta obra impressa em 1528 viria a integrar a publicação “oficial” de 1529, facto que originaria uma persistente confusão entre ambas, até porque aquela que pode considerar-se a versão primitiva, o Libro Áureo, apesar do aparente repúdio do autor, continuaria a ser objecto de sucessivas edições autónomas. Isso mesmo dizia expressamente Antonio de Guevara no prólogo do Relox de Príncipes, sustentando que a impressão do Marco Aurelio fora feita sem seu consentimento. Após referir que, a pedido do imperador, que se encontrava doente na altura, lhe oferecera o manuscrito, incompleto, do Libro Áureo, Guevara afirmava a sua mágoa por, sem poder controlar esse processo, o manuscrito ter sido copiado e recopiado na corte pelas mais diversas mãos, e progressivamente adulterado, publicando-se uma versão na qual ele próprio não se reconhecia.

Corte, poder e utopia: o relox de príncepes (1529). De Fr. António de Guevara e a sua fortuna na Europa do século XVI

Antonio de Guevara (1480?-1545), es una figura singular de la cultura ibérica del siglo XVI. La proximidad al emperador Carlos V marcará su trayectoria personal y su producción literaria. La publicación, en 1528, del Libro Aureo de Marco Aurelio, dará cominezo a una carrera literaria que hará de Guevara uno de los autores más leidos y apreciados de la Europa del siglo XVI. Procurando inscribir su carrera vital en la coyuntura histórica de la España de su tiempo, este texto analiza l trayectoria y fortuna del Relox de Príncipes, publicado en 1529, y su irradiación ibérica y europea, con especial incidencia para el caso portugués.

A Utopia na Literatura Fantástica: um exemplo

Análise do episódio do "Afundamento de Númenor" como uma utopia inserida na obra de J. R. R. Tolkien

Is there space to build one more transshipment terminal within Portuguese territory?

NSBE - UNL