RCAAP Repository

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Background: Acquired perforating dermatosis (APD) comprises an uncommon group of skin disorders that develop in adulthood in association with systemic diseases. The aim of this study was to characterize clinicopathologic features and treatment outcomes in a series of patients diagnosed with APD. Methods: Retrospective study of all patients diagnosed with an APD over a 10-year period (2009-2018) at a tertiary teaching hospital in Lisbon, Portugal. Results: Fifty-seven patients with APD were identified. Thirty-five patients presented lesions in multiple anatomic areas (61.4%), and the lower limbs were the most common location. Forty-six patients reported pruritus (80.7%), which was classified as severe in 21 of them (36.8%). An underlying systemic disease was identified in 53 patients (93.0%). Diabetes mellitus (DM) and chronic kidney disease (CKD) were the most common associated systemic diseases, but psychiatric disorders, malignancies, and chronic infections were present in a significant number of patients. The combination of topical steroids with antihistamines was the most prescribed initial treatment, but only 37.8% of the patients had a complete response. Acitretin, systemic steroids, and phototherapy were the treatments associated with the best outcome. Conclusion: Acquired perforating dermatosis can be associated with many systemic disorders that have pruritus as a common factor. Chronic viral infections and an occult malignancy should be sought, particularly in the absence of DM and CKD. The management of APD is challenging and is best achieved with the control of the underlying systemic diseases.

Kidney transplant (KT) recipients have an increased risk for urothelial carcinoma. A role for JC virus (JCV) in human cancers is not yet proved but there is an increasingly reported association between BK virus (BKV) nephropathy and renourinary neoplasms. We report a KT recipient who developed a high-grade urothelial carcinoma 5 years after a diagnosis of JCV nephropathy and 9 years after kidney transplantation. Neoplastic tissue was positive for JCV DNA by real-time polymerase chain reaction (PCR). Immunochemical staining showed strong positivity for cell cycle markers (p16, p53, and Ki67) and for early viral protein JCV large T antigen (JCV LTag; using a broad polyomavirus antibody); however, late viral protein (VP1) stained negative. In contrast, in non-neoplastic urothelium, JCV DNA and all immunochemical markers were negative. These facts suggest that malignancy was induced by JCV. To the best of our knowledge, this is the first report of urothelial high-grade carcinoma associated with JCV nephropathy in a KT recipient.

O Modelo da Complementaridade Paradigmática segue uma perspectiva integrativa e conceptualiza sete pares de necessidades psicológicas (Vaz-Velho, Vasco & Conceição, 2011; Vaz-Velho & Vasco, 2010; Vasco, 2011, 2010, 2009a, 2009b), concebendo o bem-estar como resultante da regulação de satisfação das necessidades através de um processo contínuo de negociação e equilíbrio dos pares dialécticos. Com base na literatura da área da produtividade e do lazer, numa perspectiva psicológica, construiu-se uma escala de avaliação do grau de regulação do par de necessidades Produtividade/Lazer. Esta escala foi aplicada a 562 participantes através de uma plataforma Web e os resultados foram relacionados com as escalas de Bem-Estar Psicológico e Distress Psicológico, do Inventário de Saúde Mental (ISM). Os resultados apoiam a consistência interna dos instrumentos e mostram o contributo das variáveis na variância dos resultados, revelando a relação positiva da Produtividade e do Lazer com o Bem-Estar Psicológico e negativa com o Distress Psicológico. Dividindo os sujeitos por 4 grupos com base nas medianas dos resultados no par de necessidades Produtividade/Lazer, o grupo de resultados mais elevados nos dois pólos revela resultados mais elevados de Bem-Estar Psicológico e mais baixos de Distress Psicológico, quando comparado com os restantes grupos. Apresentam-se as limitações do estudo, as implicações dos resultados para futuras investigações e para a prática psicoterapêutica e sugerem-se linhas de investigação futuras.

Protein behavior is closely regulated by a plethora of post-translational modifications (PTMs). It is therefore desirable to develop approaches to design rational PTMs to modulate specific protein functions. Here, we report one such method, and we illustrate its successful implementation by potentiating the anti-aggregation activity of a molecular chaperone. Molecular chaperones are a multifaceted class of proteins essential to protein homeostasis, and one of their major functions is to combat protein misfolding and aggregation, a phenomenon linked to a number of human disorders. In this work, we conjugated a small-molecule inhibitor of the aggregation of α-synuclein, a process associated with Parkinson's disease (PD), to a specific cysteine residue on human Hsp70, a molecular chaperone with five free cysteines. We show that this regioselective conjugation augments in vitro the anti-aggregation activity of Hsp70 in a synergistic manner. This Hsp70 variant also displays in vivo an enhanced suppression of α-synuclein aggregation and its associated toxicity in a Caenorhabditis elegans model of PD.

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Background: Staphylococcus epidermidis is a common skin commensal that has emerged as a pathogen in hospitals, mainly related to medical devices-associated infections. Noteworthy, infection rates by S. epidermidis have the tendency to rise steeply in next decades together with medical devices use and immunocompromized population growth. Staphylococcus epidermidis population structure includes two major clonal lineages (A/C and B) that present contrasting pathogenic potentials. To address this distinction and explore the basis of increased pathogenicity of A/C lineage, we performed a detailed comparative analysis using phylogenetic and integrated pangenome-wide-association study (panGWAS) approaches and compared the lineages's phenotypes in in vitro conditions mimicking carriage and infection. Results: Each S. epidermidis lineage had distinct phenotypic signatures in skin and infection conditions and differed in genomic content. Combination of phenotypic and genotypic data revealed that both lineages were well adapted to skin environmental cues. However, they appear to occupy different skin niches, perform distinct biological functions in the skin and use different mechanisms to complete the same function: lineage B strains showed evidence of specialization to survival in microaerobic and lipid rich environment, characteristic of hair follicle and sebaceous glands; lineage A/C strains showed evidence for adaption to diverse osmotic and pH conditions, potentially allowing them to occupy a broader and more superficial skin niche. In infection conditions, A/C strains had an advantage, having the potential to bind blood-associated host matrix proteins, form biofilms at blood pH, resist antibiotics and macrophage acidity and to produce proteases. These features were observed to be rare in the lineage B strains. PanGWAS analysis produced a catalog of putative S. epidermidis virulence factors and identified an epidemiological molecular marker for the more pathogenic lineage. Conclusion: The prevalence of A/C lineage in infection is probably related to a higher metabolic and genomic versatility that allows rapid adaptation during transition from a commensal to a pathogenic lifestyle. The putative virulence and phenotypic factors associated to A/C lineage constitute a reliable framework for future studies on S. epidermidis pathogenesis and the finding of an epidemiological marker for the more pathogenic lineage is an asset for the management of S. epidermidis infections.

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Tachyplesin I, II and III are host defense peptides from horseshoe crab species with antimicrobial and anticancer activities. They have an amphipathic β-hairpin structure, are highly positively-charged and differ by only one or two amino acid residues. In this study, we compared the structure and activity of the three tachyplesin peptides alongside their backbone cyclized analogues. We assessed the peptide structures using nuclear magnetic resonance (NMR) spectroscopy, then compared the activity against bacteria (both in the planktonic and biofilm forms) and a panel of cancerous cells. The importance of peptide-lipid interactions was examined using surface plasmon resonance and fluorescence spectroscopy methodologies. Our studies showed that tachyplesin peptides and their cyclic analogues were most potent against Gram-negative bacteria and melanoma cell lines, and showed a preference for binding to negatively-charged lipid membranes. Backbone cyclization did not improve potency, but improved peptide stability in human serum and reduced toxicity toward human red blood cells. Peptide-lipid binding affinity, orientation within the membrane, and ability to disrupt lipid bilayers differed between the cyclized peptide and the parent counterpart. We show that tachyplesin peptides and cyclized analogues have similarly potent antimicrobial and anticancer properties, but that backbone cyclization improves their stability and therapeutic potential.

Amyotrophic lateral sclerosis (ALS) is usually sporadic, but 20% of European ancestry cases have a family history of ALS or frontotemporal dementia (FTD). More than 30 genes confer a higher risk for ALS, and C9orf72, TARDBP, SOD1 and FUS account for nearly 70% of all familial (fALS) cases. Tank-binding kinase 1 (TBK1) is an established causal gene associated with 1% of fALS and/or FTD. It codes for a multifunctional kinase involved in multiple cellular processes, such as neuroinflammation and autophagy. Both loss-of-function (LoF) and missense mutations are associated with an increased risk for ALS-FTD spectrum and mutations that cause a 50% reduction of TBK1 protein levels are considered pathogenic.

A memória precisa dos que a motivam e dos que a visitam. Uns, criadores no seu tempo, escrevem as suas delicadas articulações sem saber o seu destino. Outros, nos tempos vindouros, tentam captar a intentio auctoris sabendo que ela se esconde no tecido da criação, nos processos dos artistas. Estes talvez possam ter um ponto de vista que acrescenta algo de novo á matéria do conhecimento. A cultura, a memória dos outros, é também a nossa memória, aqui considerada em perigo. Para salvaguardar a memória pode-se revisitá-la, registá-la, criticá-la, revivê-la. Os espaços discursivos não são assim tantos, mas decerto que a Revista Gama é um deles: aqui se guardam visitas a criadores, se anotam e registam, aqui se resiste. Assim se convocam os artigos que compõem este número da revista Gama. O objetivo é presente: criar discursos de salvaguarda das propostas artísticas mais ou menos dispersas, mais ou menos em perigo, mais ou menos em desligamento. São reativações, renovações de olhares, releituras

O conhecimento da história das instituições e da sua interacção com o meio social em que se inseriram e actuaram depende muito da existência do seu arquivo. No entanto, quando as instituições não conservaram os seus sistemas de informação, por vicissitudes várias, as possibilidades de reconstituir a sua história ficam muito limitadas. Este pequeno trabalho tem como objectivo apresentar a tentativa da reconstituição de um sistema de arquivo pretérito a partir dos documentos sobreviventes conservados pelo produtor e por outras instituições que mantiveram com ele relações hierárquicas, temporais e associativas. Seleccionou-se a Santa Casa da Misericórdia de Sines, alvo de um estudo sistemático publicado este ano (Patrício, 2016), e um tempo em específico: a Época Moderna.

Esta Newsletter (NL) resulta de uma parceria entre o Instituto de Saúde Baseada na Evidência e a Cochrane Portugal, e tem como objectivo disponibilizar informação sobre áreas interessantes para a prática clínica, com base na melhor evidência científica. São incluídos estudos relevantes, criticamente avaliados pela sua validade, importância dos resultados e aplicabilidade prática, resumidos numa óptica de suporte à decisão. É dada prioridade a estudos de causalidade incluindo-se ainda, quando justificado, estudos qualitativos e metodológicos, assim como revisões científicas. O conteúdo da NL é da exclusiva responsabilidade do(s) seu(s) autor(es).

It has been shown that Notch signaling mediated by ligands of both Jagged and Delta families expands the hematopoietic stem cell compartment while blocking or delaying terminal myeloid differentiation. Here we show that Delta1- and Jagged1-expressing stromal cells have distinct effects on the clonogenic and differentiation capacities of human CD34(+) CD38(+) cells. Jagged1 increases the number of bipotent colony-forming unit-granulocyte macrophage (CFU-GM) and unipotent progenitors (CFU-granulocytes and CFU-macrophages), without quantitatively affecting terminal cell differentiation, whereas Delta1 reduces the number of CFU-GM and differentiated monocytic cells. Expression analysis of genes coding for Notch receptors, Notch targets, and Notch signaling modulators in supernatant CD34(+) cells arising upon contact with Jagged1 and Delta1 shows dynamic and differential gene expression profiles over time. At early time points, modest upregulation of Notch1, Notch3, and Hes1 was observed in Jagged1-CD34(+) cells, whereas those in contact with Delta1 strikingly upregulated Notch3 and Hes1. Later, myeloid progenitors with strong clonogenic potential emerging upon contact with Jagged1 upregulated Notch1 and Deltex and downregulated Notch signaling modulators, whereas T/NK progenitors originated by Delta1 strikingly upregulated Notch3 and Deltex and, to a lesser extent, Hes1, Lunatic Fringe, and Numb. Together, the data unravel previously unrecognized expression patterns of Notch signaling-related genes in CD34(+) CD38(+) cells as they develop in Jagged1- or Delta1-stromal cell environments, which appear to reflect sequential maturational stages of CD34(+) cells into distinct cell lineages.

O presente trabalho de investigação aplicada centra-se na temática da equivalência intercultural, e consiste no estudo de uma bateria de testes de aptidões, utilizada em diversas organizações nacionais e internacionais, em contextos de avaliação psicológica – Bateria de Raciocínio Crítico (CRTB). Partiu do pressuposto de que as versões originais e as versões adaptadas de cada teste são equivalentes, e procedeu à comparação entre as versões do Reino Unido (original) e de Portugal, da Austrália e da África do Sul (adaptações), e de Portugal (original) e Moçambique (adaptação). Partindo de um total 4946 respostas a três testes de aptidões - Verbal, Numérico e Diagramático - foi efectuado o estudo do Funcionamento Diferencial dos Itens (DIF), nas versões aplicadas nos cinco países, com recurso a metodologia baseada na Teoria da Resposta ao Item (TRI), nomeadamente, pela aplicação do Modelo de Rasch. Detectou-se a presença de DIF em alguns itens, nos vários testes, o que pode comprometer a equivalência intercultural das diferentes versões. Contudo, a análise efectuada não permitiu concluir que os testes são, na sua globalidade, culturalmente enviesados, devido a limitações na qualidade dos dados amostrais disponíveis. Este estudo alertou para a necessidade de averiguar a qualidade dos conteúdos dos itens e para a conveniência da utilização conjunta de Métodos Estatísticos e dos Juízes, nas adaptações de testes, assim como para a necessidade de interpretação cautelosa, em decisões de selecção que tenham por base os resultados de instrumentos psicométricos adaptados. Adicionalmente, reuniu evidências das potencialidades e vantagens da metodologia TRI para a investigação em Psicologia Intercultural.

Cell migration is an important biological process which has been intensively studied in the past decades. Numerous techniques, mainly involving two-dimensional cell culture systems, have contributed to dissecting the essential mechanisms underlying this process. However, the development of three-dimensional cell culture and in vivo systems has shown some differences with what was previously believed to be well-established cell migration mechanisms, suggesting that two-dimensional cell motility would be a poor predictor of in vivo behaviour. Drosophila is a widely recognized model organism to study developmental and homeostatic processes and has been widely used to investigate cell migration. Here, we focus on the migration of small groups of pupal hemocytes that accumulate during larval stages in dorsal patches. We show that integrins, and other known nascent adhesion-related proteins such as Rhea and Fermitin 1, are crucial for this process and that their depletion does not affect polarization in response to environmental cues. We also present evidence for the importance of adhesion maturation-related proteins in hemocyte migration, namely Zyxin. Zyxin depletion in hemocytes leads to a significant increase of cell speed without affecting their response to a chemotactic cue. This is the first report of a systematic analysis using Drosophila melanogaster hemocytes to study adhesion-related proteins and their function in cell migration in vivo. Our data point to mechanisms of cell migration similar to those described in three-dimensional in vitro systems and other in vivo model organisms.

Background: Cancer aetiology is multifactorial and risk factors include: obesity, central adiposity, sedentarism, excessive or deficient intake of foods and/or nutrients with pro-carcinogenic effects vs protective ones. Objectives: To evaluate the pattern of nutritional status, life styles, physical activity and diet in a cohort of cancer patients. Methods: This pilot cross-sectional study was conducted in 64 patients referred for radiotherapy at the Radiotherapy Department of the University Hospital of Santa Maria (CHLN). Evaluations were: waist circumference associated with potential cardio-metabolic risk, body composition by Tetrapolar Bioimpedance Analysis (XITRON®), Body Mass Index, dietary intake pattern with a short food frequency questionnaire, physical activity with Jackson questionnaire. Results: The most frequent diagnosis were breast and colorectal cancers; 53% of patients were overweight/obese, and there was a significant correlation between this nutritional pattern and weight gain in comparison with usual weight (p<0.005). There were 78% of patients with a waist circumference above the maximum cut-off limit, indicating moderate/ high cardio-metabolic risk, and most were female patients (87%). The great majority of patients (61%) had excessive fat mass highly above the maximum recommended cut-off value, especially male patients (74%). The dietary pattern was poor in vegetables (55%) and excessive in meat and simple carbohydrates (78%); physical activity was low with a high prevalence of sedentarism. Conclusions: This population presented excessive body weight, excessive fat mass, high cardio-metabolic risk, sedentarism and an unbalanced diet poor in protective foods/nutrients. This population's life styles and nutritional pattern, may be considered of risk in oncology disease. The elevated and growing incidence of cancer in Portugal, reinforces the need for further research in order to identify nutritional factors involved in the etiology/evolution and probably prognosis of cancer.

Background: Cavotricuspid isthmus (CTI) ablation in typical atrial flutter (AFL) restores sinus rhythm in 95% of patients, which may lead to the discontinuation of oral anticoagulation during follow-up. Therefore, we aimed to systematically review the clinical impact of oral anticoagulation in the incidence of thromboembolic events (TE) after typical AFL ablation. Methods: We searched for controlled studies evaluating the impact of anticoagulation in the incidence of TE in patients submitted to AFL ablation in MEDLINE, CENTRAL, PsycINFO database (June/2021). The primary outcome was TE events (ischemic stroke or systemic embolism). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI). Statistical heterogeneity was measured through I2 metric. The confidence in the evidence was appraised with Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: Eight observational studies with 4870 patients were included. TE events were not significantly reduced (RR 1.18, 95% CI 0.59-2.36; n = 4870; GRADE very low). A meta-regression showed that for each 10% increase in the prevalence of previous AF in the studied population, anticoagulation reduced TE risk in 32%. There were no significant differences regarding bleeding events (RR 2.16, 95% CI 0.43-10.97, I2 = 0%; GRADE low), but there was a lower all-cause mortality (RR 0.24, 95% CI 0.17-0.32, GRADE low). Conclusion: The best available evidence lacks robustness and the data did not definitely associate anticoagulation after typical AFL ablation with reduced TE.

Resilience is a dynamic, multidimensional complex concept that implies risk and protective factors, adaptation, and success. Communication and language are often identified as barriers in deaf children's development. However, research linking deafness in childhood and resilience is scarce. The present comprehensive literature review aims to verify which are the predominant risk factors for this group, which protective factors may be identified and if significant differences have been found between deaf and hearing children regarding resilience. A systematic search, performed in seven databases, identified 11 articles published in peer-reviewed journals between 2000 and 2019 that met the criteria. Deaf children experience exposure to risk through obstacles in communication, language, and information failure. Consequently, differences between hearing and deaf children are related to more difficulties in emotion regulation and interpersonal relationships. Principal protective factors are a supportive family, school staff, and peers. Practical implications and recommendations for future research are provided.

O projeto Gama é um projeto de resistência que contrapõe, de modo consistente, discursos novos, que colocam em contacto novos intervenientes, novas agências, novas afinidades. É um campo de consolidação cultural que reúne os 15 autores aqui representados. O contexto é reconhecido como de viragem educativa , quando se observa uma tendência de convergência de agências na direção inclusiva, colaborativa, participativa, por parte de instituições, escolas, museus, plataformas de disseminação e de produção, artistas e educadores. O projeto Gama, e com ele, o projeto do Congresso CSO (Criadores sobre outras Obras), é um projeto que reivindica uma resistência para contrapor, de modo consistente, discursos novos, colocando em contacto novos intervenientes, gerando novas agências, favorecendo afinidades. O projeto é simples: é preciso dar a conhecer quem está por conhecer, é preciso fazer funcionar os circuitos relacionais excêntricos e antepor à colaboração um conhecimento mútuo que robustece os discursos, e origina novidade nos discursos sobre arte.