Repositório RCAAP

Photodynamic therapy (PDT) has long been used in dermatology as a therapeutic strategy for several malignant and premalignant conditions. Currently, it is approved in Europe for the treatment of actinic keratosis, squamous cell carcinoma in situ, and some forms of basal cell carcinoma, with favorable clearance rates associated with satisfying aesthetic results. Nonetheless, in the past few years, PDT has also demonstrated efficacy in many other conditions, including inflammatory and infectious dermatoses. These results, probably explained by its immunomodulatory, anti-inflammatory, and bactericidal effects, may lead to an expansion of PDT indications in the upcoming years. In this article, conditions where PDT may be useful are reviewed, thus highlighting the potential of this therapeutic modality for the dermatologist.

There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces (•)Trp and (•)O2 (-) radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO(•)) by α -tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α -tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α -tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α -tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

Bullous dermatoses are a variety of autoimmune skin diseases that are characterized by the presence of bullae or blisters. Most of these diseases are associated with substantial morbidity, and a few may result in death. Although most general approaches to the treatment and diagnosis of these entities are similar, the diagnosis of the specific disease is important, because the most appropriate dosage and timing of some commonly used medications vary considerably. The review covers the management of main autoimmune bullous dermatoses, including bullous pemphigoid and pemphigus vulgaris, linear IgA dermatosis, dermatitis herpetiformis, and bullous systemic lupus erythematosus.

Diabetes mellitus (DM) is a chronic condition, the prevalence of which is increasing in Europe. Continuous glucose monitoring systems, such as FreeStyle Libre (Abbott Diabetes Care, UK) have improved DM management. This device is applied to the skin through an adhesive and remains in place for up to 14 days, dynamically measuring interstitial glucose levels.

Resumo alargado disponível em português e inglês

Esta investigação estuda o desenvolvimento do pensamento algébrico de futuros professores e educadores e a sua aprendizagem sobre o ensino aprendizagem da Álgebra nos primeiros anos, no âmbito de uma experiência de formação com uma abordagem exploratória, com particular enfoque em situações que envolvem modelação matemática. O estudo segue uma metodologia qualitativa, usando estudos de caso. Os participantes são formandos de uma turma da unidade curricular Álgebra e Funções da Licenciatura em Educação Básica, leccionada pela primeira autora. São seleccionados quatro formandos para estudos de caso. Os dados são recolhidos por dois questionários realizados aos 20 formandos da turma antes e depois da realização da experiência de formação. Foram ainda realizadas três entrevistas individuais em diferentes momentos da experiência de formação aos quatro formandos, tendo por base tarefas matemáticas que abordam diferentes tópicos da Álgebra. São ainda fontes de dados a observação participante e os documentos produzidos pelos formandos. Este artigo apresenta dados relativos ao trabalho desenvolvido pela turma e, de um modo particular, por Alice no âmbito do trabalho da modelação matemática. Os resultados referem-se ao desenvolvimento do pensamento algébrico dos formandos e à sua compreensão do ensino e da aprendizagem da Álgebra nos primeiros anos, no âmbito da experiência de formação, quando analisam produções de alunos do 6.º ano e reflectem sobre a abordagem de ensino seguida pela professora para desenvolver nos seus alunos a capacidade de resolver situações de modelação. Os formandos identificam aspectos fundamentais que visam o desenvolvimento do pensamento algébrico dos alunos.

The English dramas of Fernando Pessoa are virtually unknown. Pessoa’s archive includes fragments of Marino, Prometheus Rebound (or Revinctus), and Duke of Parma—three dramatic projects that remain almost entirely unpublished. This paper is the first of two aiming to present Marino, the earliest of these English dramas. The editorial introduction includes a brief background on Pessoa’s drama, a discussion of the state of the art of Pessoa’s English plays, notes on defining and dating the corpus of Marino, a commentary on the meter and versification employed by Pessoa, and an explanation of the transcription criteria and symbols used. The edition includes half of Marino’s corpus, featuring transcriptions, facsimiles, and a critical apparatus of: 23 datable fragments (14 of them previously unpublished) written between 1903–1908; an outline of the play likely made in 1906; and 13 lists in which Pessoa refers to the drama between 1903–1914.

Christian poetry, and Biblical epic in particular, is intensely self-conscious. Both Greek and Latin Christian poets begin or end their compositions, paraphrases and centos with poetological reflections on the value and objectives of their works. The fifth-century Paraphrase of the Gospel according to John is an anomaly in this tradition. While Nonnus’ mythological epic, the Dionysiaca, is heavily self-conscious in that it includes a strong authorial voice as well as an extensive prooemium and an interlude, the Christian Paraphrase has no prooemium, epilogue or interlude, and its narrator never identifies himself. This article examines two passages in the Paraphrase where subtle, implicit poetological reflections may be detected, and then explores the reasons why Nonnus may have chosen to deny the Paraphrase a clear (meta)literary identity. It argues that Nonnus’ poem presents itself as the Gospel of John, and that its narrator ‘becomes’ John the Evangelist in a spiritual exercise which is indebted to Origen’s views on that Gospel.

No summary/description provided

No summary/description provided

No summary/description provided

Lamentations Rabbah Proem 24, a late ancient rabbinic midrash, is in many ways a unique text within the entire rabbinic corpus. It presents an extraordinary array of characters (including Abraham, Moses, the Torah, and even the alphabet) who are called upon to placate God, but fail. As their quest proves inconclusive, the biblical Rachel jumps into the fray to tell her story: how out of sisterly compassion she allowed Leah to take her own place in the conjugal bed on “her” wedding night. Disclosing to her sister the secretive “signs” she had shared with Jacob, Rachel crawled under the nuptial bed to respond to Jacob whenever he spoke. This scandalous autobiography transforms an apparent instance of illicit sex, the ideal material for theatrical stage mimes, into an act of martyrdom and sublime compassion. This article argues that the performance culture of the late ancient Mediterranean world provides the key for assessing this text’s originality. We begin with an analysis of the text, drawing attention to its theatrical qualities and its relationships with contemporary visual imagery (mosaics) and texts from outside the rabbinic milieu (Christian Apocrypha). We then examine the casting of midrashic Rachel as a response to both the mimic adulteress and the Christian martyr. Finally, we consider rabbinic familiarity with mime, particularly with its usefulness as a social mediator and agent of collective catharsis. It is precisely these aspects of mimic performance, we argue, that Rachel’s vignette appropriates in this fascinating rabbinic text.

This study's purpose is to systematically review the literature to identify the most recent library practices against fake news. Libraries are perceived as an important player against the fake news phenomenon. However, this role is often cornered in a positive self-perception of the work of librarians. This article investigates the tangible practices of libraries, discusses their efficiency, and provides a categorization of those practices. It was performed a systematic literature review of the last three years to retrieve the most recent library practices. After the extraction, with a final set of 27 documents, a multi-step qualitative analysis and a categorization were developed. Findings show most studies emphasize academic libraries practices and are mainly focused on information literacy instruction. The current debate is around strategies that intend to reiterate an authority-based source evaluation versus the challenge to recognize an emotional-based reaction to fake news in a post-truth world, and the need to scout libraries' new routes.

The present paper aims to study the item i in Kriol, the Portuguese-related creole of Guinea-Bissau. More specifically, i is 3SG subject pronoun and also functions as copula in individual-level predication. As a pronoun, i may also occur as resumptive to topic-comment structures. On the basis of the striking similarity between copular clauses with i and topic-comment structures with resumptive i, I will argue that the pronoun i and the copula i are not simple homophones, but represent two different syntactic functions of the very same item. I assume that the copula i derives from the resumptive pronoun i in topic-comment structures. This kind of grammaticalization of the pronoun into a copula, also known as copularization, is well documented in a number of languages. The main goal of the paper will be to reconstruct the path of grammaticalization of the copula i and to provide a syntactic account of it. I will follow Lohndal (2009) in assuming that this kind of grammaticalization, motivated by the ambiguity caused by certain topic-comment structures with resumptive pronoun, corresponds to an economy-oriented structural change: the pronoun shifts from the specifier to the head of the predication phrase (PredP). This shift is part of the type of structural changes described as copula cycle (see e.g. van Gelderen 2004, 2008, 2009, 2011, 2015; Lohndal 2009). Given that 3SG i is arguably a subject clitic and cannot sit in the specifier of PredP, I will argue, on the basis of Kihm’s (2007) paper, that in the proto-creole that gave rise to Kriol and the other Upper Guinea creoles there was a 3SG nonclitic pronoun *ele. It occurred as resumptive to topic-comment structures and was later reanalysed as a copula.

O projeto de investigação LORIVAI - Loulé Velho e o paleoestuário da ribeira de Carcavai tem como objetivo principal o estudo do sítio romano de Loulé Velho (Quarteira, Loulé), do papel que desempenhou na dinâmica do povoamento local/regional e da economia desde a época romana à Antiguidade Tardia (séc. I-VI d.C.). Os trabalhos arqueológicos que aí foram sendo intermitentemente realizados nos últimos 50 anos permitiram a identificação de estruturas ligadas à produção de preparados de peixe (cetariae), outras associadas à produção de vinho ou azeite (contrapeso cilíndrico) e uma necrópole. A destruição contínua que tem sofrido pelo recuo da arriba e avanço da linha do mar levou à recuperação de um enorme volume de achados arqueológicos (centenas de fragmentos de objectos de cerâmica, osso, metal, vidro, etc.) que estão a ser objecto de estudo sistemático no âmbito deste projecto, que se pretende colaborativo e participado também pela população do concelho Loulé.

Apesar de nunca ter apresentado um conceito suficientemente preciso de thema/themata, Gerald Holton teve desde sempre a preocupação de alertar para a possível confusão entre os themata e diversas outras entidades que, podendo em alguns aspetos assemelhar-se aos themata, são, contudo, de natureza e de funcionamento distintos e como tal devem ser consideradas. É neste contexto de delimitação que surgem os paradigmas, de Thomas Kuhn, relativamente aos quais Gerald Holton sempre fez questão de contrapor os seus themata. Neste artigo apresenta-se uma análise comparativa que identifica diferenças essenciais mas também relações entre estes dois importantes conceitos da epistemologia do século XX, um inscrito numa epistemologia continuista (os themata) e outro epistemologicamente descontinuista (os paradigmas).

Este estudo apresenta a análise e interpretação da actividade desenvolvida pelos alunos de uma turma de 7.º ano de escolaridade, participando ao longo de um ano lectivo numa Comunidade Virtual de Aprendizagem (CVA) construída no contexto da disciplina de Francês. O problema central de investigação consiste em compreender de que forma a Comunidade Virtual de Aprendizagem contribui para o desenvolvimento das capacidades de comunicação em língua estrangeira (oral e escrita) e de utilização pertinente dessa língua. O problema enunciado foi operacionalizado através das seguintes questões: 1) Como comunicam os alunos na Comunidade Virtual de Aprendizagem, construída no âmbito da disciplina de Francês? 2) De que modo a participação na Comunidade Virtual de Aprendizagem contribui para a aprendizagem da língua e da cultura francesas? 3) Como se comportam e que relações estabelecem os jovens enquanto membros da Comunidade Virtual de Aprendizagem, ou seja, como interagem nesse espaço virtual? O quadro teórico propõe e discute conceitos e perspectivas que caracterizam a natureza e o papel das ferramentas Web 2.0, em geral, e das comunidades virtuais de aprendizagem, em particular, no processo de ensino/aprendizagem das línguas estrangeiras. Considera ainda a interacção social no processo de ensino/aprendizagem, à luz do paradigma comunicativo na aprendizagem da língua e tendo em conta o desenvolvimento da competência plurilingue e pluricultural dos indivíduos. Adoptou-se neste estudo uma metodologia de investigação qualitativa, com o design de estudo de caso. A recolha de dados incluiu a observação participante, entrevistas aos alunos, notas de campo e documentos produzidos pelos alunos. Os resultados do estudo revelam uma aprendizagem da língua francesa sustentada pela prática e pelo sentimento de pertença à CVA. Foi possível caracterizar detalhadamente o papel da comunicação realizada através da participação na CVA, destacando-se a imersão na língua, o enriquecimento dos conteúdos de aprendizagem e o incremento do gosto pela disciplina. Verificou-se uma forte interdependência entre participação e aprendizagem. As relações e interacções estabelecidas no âmbito da CVA incluem traços de uma comunidade de prática, verificando-se que os alunos aprendem e sentem que aprendem pela interacção regular no espaço virtual da CVA.

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.

Despite the recent advances involving molecular studies, the neonatal cholestasis (NC) diagnosis still relays on the expertise of medical teams. Our aim was to develop models of etiological diagnosis and unfavourable prognosis which may support a rationale diagnostic approach. We retrospectively analysed 154 patients born between January 1985 and October 2019. The cohort was divided into two main groups: (A) transient cholestasis and (B) other diagnosis (with subgroups) and also in two groups of outcomes: (I) unfavourable and (II) favourable. Multivariate logistic regression analysis identified the lower gestational age as the only variable independently associated with an increased risk of transient cholestasis and signs and/or symptoms of sepsis with infectious or metabolic diseases. Gamma-glutamyl transferase serum levels > 300 IU/L had a positive predictive value for both diagnosis of biliary atresia and for alpha-1-antitrypsin deficiency (A1ATD) and for unfavourable prognosis. A model of diagnosis for A1ATD (n = 34) showed an area under the ROC curve = 0.843 [confidence interval (CI): 0.773-0.912].Conclusion: This study identified some predictors of diagnosis and prognosis which helped to build a diagnostic decision algorithm. The unusually large subgroup of patients with A1ATD in this cohort emphasizes its predictive diagnostic model. What Is Known • The etiological diagnosis of neonatal cholestasis (NC) requires a step-by-step guided approach, and diagnostic models have been developed only for biliary atresia. • Current algorithms neither address the epidemiology changes nor the application of the new molecular diagnostic tools. What Is New • This study provides diagnostic predictive models for patients with A1ATD, metabolic/infectious diseases, and transient cholestasis, and two models of unfavourable prognosis for NC. • A diagnostic decision algorithm is proposed based on this study, authors expertise and the literature.

Colorectal cancer (CRC) is the third most common cancer in the world and the second leading cause of mortality. CRC survival rates are dictated by the stage at which the disease is detected, and in early stages the survival rate may reach more than 90%. The inflammatory process of the mucosa may be closely linked to both the cancer initiation process and the disease development and progression. The activity of molecules such as matrix metalloproteinases (MMPs) is crucial for the remodeling of the tumor microenvironment, having major implications in the inflammatory, migratory and angiogenic processes, thus promoting greater tumor malignancy. Several studies on bioactive polypeptides from leguminous plants have shown anti-inflammatory, antimigratory and anti-MMP activity, being considered this activity, a strategy to prevent the development of CRC and / or progression of CRC to invasive and metastatic states. Deflamine is a polypeptide oligomer found in white lupine (Lupinus albus) seeds with a great anti-inflammatory potential, as it was shown to inhibit MMP-9 activity and further to induce an improvement of colonic mucosa profile in animal ulcerative colitis disease. In in vitro studies, deflamine was found to inhibit the migration of CRC cell lines besides inhibiting MMP-9 activity. In this sense, the objective of this study was to explore the overall potential anti-tumor role of deflamine in vitro and in zebrafish in vivo model. Our results demonstrated that deflamine has inhibitory activity on CRC cell lines HT29 and SW480, both for the migratory activity (P = 0.008 and P = 0.011, respectively) and for gelatinases activity (P = 0.003 and P < 0.001, respectively). For in vivo analyses with zebrafish xenografted with HCT116 cell line, deflamine showed anti-tumor functions, promoting nearly four-fold inhibition of tumor growth in treated animals compared to the control group (P = 0.0003). We found that deflamine promoted more than two and half-fold increase in apoptosis in our model of zebrafish treated animals when compared to controls (P < 0.0001). Our results suggest an important anti-tumor role for deflamine, highlighting the potential of this polypeptide oligomer in future therapeutic applications as a nutritional complement for CRC patients. Nevertheless, more studies are needed in order to understand the molecular mechanisms contributing to deflamine functions either in cancer or other inflammatory-related diseases.