Risk-benefit assessment of Bacillus Calmette-Guérin vaccination, anti-phenolic glycolipid I serology, and Mitsuda test response: 10-year follow-up of household contacts of leprosy patients

Abstract: INTRODUCTION: Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guérin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. METHODS: This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. RESULTS : Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoption of these combined assays may impose measures for leprosy control strategies.

A ameaça terrorista em Portugal

orismo de inspiração fundamentalista islâmica. Considerando que a Europa ainda continua a ser o principal bastião ocidental dos terroristas de inspiração fundamentalista islâmica, e o facto de existirem portugueses a combater na jihad, no estrangeiro, o risco aumenta consideravelmente. No entanto, não é a prioridade máxima da Al-Qaeda, em particular da Al Qaeda do Magrebe Islâmico, bem como do Estado Islâmico, enquanto nova ameaça, atingir o nosso minúsculo país, mas a probabilidade aumenta consoante o nível de proficiência das polícias e serviços de informações europeus no combate ao terrorismo, isto é, quanto maior for o nível de segurança dos países influentes, como é o caso da França, da Alemanha, da Inglaterra, maior é a probabilidade de sermos atacados, porque os terroristas ao não conseguirem atingir estes países atingirão os de pequena influência, se estes estiverem mais debilitados em termos de segurança. Além disso, a Região Sul de Portugal fez parte do grande califado islâmico durante algum tempo da nossa história, o que potencia também esta ameaça no nosso país, tendo em conta os objetivos estratégicos da Al-Qaeda e do Estado Islâmico, que pretendem a implantação a nível mundial de um califado islâmico. Por último, alguns setores da comunidade muçulmana em Portugal, devem merecer uma atenção especial das autoridades.

Optimization of production of anti-cancer vaccines based on dendritic cells

Cancer remains as one of the top killing diseases in first world countries. It’s not a single, but a set of various diseases for which different treatment approaches have been taken over the years. Cancer immunotherapy comes as a “new” breath on cancer treatment, taking use of the patients’ immune system to induce anti-cancer responses. Dendritic Cell (DC) vaccines use the extraordinary capacity of DCs’ antigen presentation so that specific T cell responses may be generated against cancer. In this work, we report the ex vivo generation of DCs from precursors isolated from clinical-grade cryopreserved umbilical cord blood (UCB) samples. After the thawing protocol for cryopreserved samples was optimized, the generation of DCs from CD14+ monocytes, i.e., moDCs, or CD34+ hematopoietic stem cells (HSCs), i.e, CD34-derived DCs, was followed and their phenotype and function evaluated. Functional testing included the ability to respond to maturation stimuli (including enzymatic removal of surface sialic acids), Ovalbumin-FITC endocytic capacity, cytokine secretion and T cell priming ability. In order to evaluate the feasibility of using DCs derived from UCB precursors to induce immune responses, they were compared to peripheral blood (PB) moDCs. We observed an increased endocytosis capacity after moDCs were differentiated from monocyte precursors, but almost 10-fold lower than that of PB moDCs. Maturation markers were absent, low levels of inflammatory cytokines were seen and T cell stimulatory capacity was reduced. Sialidase enzymatic treatment was able to mature these cells, diminishing endocytosis and promoting higher T cell stimulation. CD34-derived DCs showed higher capacity for both maturation and endocytic capacity than moDCs. Although much more information was acquired from moDCs than from CD34-derived DCs, we conclude the last as probably the best suited for generating an immune response against cancer, but of course much more research has to be performed.

The role of the intelligence service in preventing and combating transnational terrorism

Outrora dominado por ameaças provenientes de Estados-nação, o cenário global actual, dominado por uma rápida mudança de poderes que nos apresenta uma interacção complexa entre múltiplos actores, onde inimigos desconhecidos, anteriormente bem identificados, é actualmente controlado por grupos terroristas bem preparados e bem organizados. Hezbollah é reconhecido como um dos grupos terroristas mais capazes, com uma extensa rede fora do Líbano dedicada a tráfico de droga, armas e seres humanos, tal como o branqueamento de capitais para financiar o terrorismo, representando um grande foco de instabilidade à segurança. Como instrumento de Estado, os serviços de informações detêm a capacidade de estar na linha da frente na prevenção e combate ao terrorismo. Todavia, para compreender este fenómeno é necessário analisar os actores desta ameaça. À luz desta conjuntura, esta dissertação está dividida em três capítulos principais que visam responder às seguintes questões fundamentais: O que é o terrorismo? Como opera um grupo terrorista transnacional? Será que os serviços de informações têm as ferramentas necessárias para prevenir e combater estas ameaças?

Raptos, sequestros e tomada de reféns

In this thesis we address the paradigms and inconsistencies involving crisis kidnappings and hostage-taking. This work particularly focuses on foreign hostages seized by terrorists and guerrilla movements. It highlights major global events that have contributed to the collective awareness of the phenomenon and the evolution of international agreements and protocols. We focus on the episodes involving Portugal or Portuguese abroad, particularly on the kidnapping of Portuguese in the Cabinda enclave. It also deals with the problems associated with the payment of ransoms, the increasing involvement of private agents in addressing these crises, and incongruities in the motivations of the kidnappers.

Hemolytic disease of the newborn due to anti-U

Anti-U is a rare red blood cell alloantibody that has been found exclusively in blacks. It can cause hemolytic disease of the newborn and hemolytic transfusion reactions. We describe the case of a female newborn presenting a strongly positive direct antiglobulin test due to an IgG antibody in cord blood. Anti-U was recovered from cord blood using acid eluate technique. Her mother presented positive screening of antibodies with anti-U identified at delivery. It was of IgG1 and IgG3 subclasses and showed a titer of 32. Monocyte monolayer assay showed moderate interaction of Fc receptors with maternal serum with a positive result (3.1%). The newborn was treated only with 48 hours of phototherapy for mild hemolytic disease. She recovered well and was discharged on the 4th day of life. We conclude that whenever an antibody against a high frequency erythrocyte antigen is identified in brown and black pregnant women, anti-U must be investigated.

A maritimidade portuguesa : a extensão da plataforma continental

As potencialidades da plataforma continental estendida são enormes e variadas, desde as que podem ser obtidas através de sectores tradicionais – como portos e marinas ou turismo náutico – até as que advirão de novos sectores como a exploração dos fundos do mar ou a energia das ondas, entre outras. Com efeito, devido ao alargamento resultante das negociações nas Nações Unidas, é praticamente garantido que Portugal passe a controlar um espaço marítimo, acrescido de 2.1 milhões de km2, isto é, vinte vezes a extensão da sua superfície terrestre. A maritimidade de Portugal constitui um traço profundamente marcado na sua história, bem como nas suas tradicionais práticas económicas, sociais e simbólicas. Na verdade, os últimos anos testemunharam a criação de um amplo consenso quanto ao papel determinante que o desenvolvimento costeiro, a superfície e o comprimento dos limites do “Mar Português” terá no futuro do país. Da articulação entre o Território Nacional, o Oceano Atlântico e o Continente Europeu, associada à confluência das vias de comunicação marítimas que ligam a Europa à América do Norte e do Sul configurar-e-ão os aspectos essenciais do designado “Espaço Estratégico de Interesse Nacional Permanente”. A área geográfica prioritária para o desenvolvimento das acções militares de Defesa Nacional e dos interesses vitais permanentes inclui assim – para além do Território Nacional – o Espaço Interterritorial, o Mar Territorial (MT), o espaço aéreo sob responsabilidade nacional e a Zona Económica Exclusiva (ZEE). O País é titular de soberania no território continental e nos arquipélagos da Madeira dos Açores, para além de estar comprometido com alguns Estados da CPLP, que têm no Atlântico Sul uma importante e poderosa presença. Pela geografia e pela definição dos interesses dos Estados e dos grandes espaços em que estão incluídos, Portugal está na articulação da segurança do Atlântico Norte com a segurança do Atlântico Sul. Esta realidade acarreta novos desafios para a Defesa Nacional, assumindo como preocupações acrescidas o terrorismo, o tráfico e a pirataria marítimas, entre outras.

Segurança e criminalidade organizada

Globalization brought some deep changes to the world (dis)order. Nowadays, more than in other moment in history, we are closer to the ones physically far, living in “global village” called by Marshall McLuhan (1962). The concepts and premises built in this new order, have totally broken with the ones that “came out from Westphalia”, which had last to the end of the cold war, like, for example, the concept of security. Since then, security has been facing one of its biggest transformations ever, completely disrupting the state border based idea and starting to be extended to other domains, as human, economic, environmental and IT security, among others. In this global and interdependent environment, “new” threats and risks have raised, which are demanding a comprehensive approach from the States, international organizations and other actors, to allow the analysis and understanding its impacts on the various society sectors and orders. Inside the enormous challenges to the global security, it is important to regard the organized crime, which covers, by itself, a set of threats and risks, enhanced by its connection to other types of criminality, such as terrorism. The goals pursued and the tactics used by criminal organizations during the perpetration of illegal activities, specially the drug smuggling, have impact in an wide spectrum of the social, economic financial and politic dimensions, which should not be underestimated, otherwise our own security may be compromised. Therefore, the current investigation intends to be an important catalyst to the idea debate inside security scope, through the analysis of the organized crime and the drug smuggling, adding to a discussion of this issue, which should be deeper and holistic, aiming a better understanding of the challenges provided by our society.

Açaí (Euterpe oleracea mart.) e camu-camu (Myrciaria dubia (H.B.K.) Mc Vaugh) possuem ação anti anêmica?

Avaliou-se o impacto da utilização do açaí e camu-camu em pré-escolares de uma Unidade Filantrópica de Manaus-AM. Foram selecionadas 85 crianças voluntárias, de dois a seis anos incompletos, de ambos os sexos, distribuídas aleatoriamente em 5 grupos, tendo como fonte de ferro e vitamina C: açaí e açaí + camu-camu, perfazendo um total de 2 mg de ferro e 40 mg de ácido ascórbico, assim como o ferro aminoácido quelato na concentração de 1 e 2 mg de ferro. O ferro foi distribuído diariamente na colação por um período de 120 dias. Na caracterização da anemia considerou-se o ponto de corte de hemoglobina <11g/dL. Os resultados demonstraram que de um universo de 85 crianças 6 (7%) apresentaram um quadro de desnutrição crônica, sendo ao final da intervenção reduzido para 4 (4,7%). O maior impacto da utilização do açaí foi como fonte energética, refletido no ganho de peso significativo das crianças (1,76 kg), mesmo quando adicionado de camu-camu (1,69 kg). Em relação a concentração de hemoglobina, não foi constatada diferença significativa entre as crianças dos diferentes grupos, independente da fonte de ferro: açaí (0,71 g/dL); açaí + camu-camu (0,60 g/dL), Ferro 2 mg (0,88 g/dL); água (0,85 g/ dL) e Ferro 1 mg (0,54 g/dL). Entretanto, a recuperação de crianças anêmicas foi maior no grupo que recebeu ferro aminoácido quelato na concentração de 2 mg de ferro. Conclui-se que o açaí tem um grande potencial como fonte energética e pouca expressividade como fonte de ferro, mesmo adicionado de camu-camu.

Biofunctionalization of titanium surfaces for dental implants: osteogenic, anti-microbial and tribocorrosion resistant surfaces

PhD thesis in Biomedical Engineering

Assessment of a protease inhibitor peptide for anti-ageing

Ageing and skin exposure to UV radiation induces production and activation of matrix metalloproteinases (MMPs) and human neutrophil elastase (HNE). These enzymes are known to break down the extracellular matrix (ECM) which leads to wrinkle formation. Here, we demonstrated the potential of a solid-in-oil nanodispersion containing a competitive inhibitor peptide of HNE mixed with hyaluronic acid (HA), displaying 158 nm of mean diameter, to protect the skin against the ageing effects. Western blot analysis demonstrated that activation of MMP-1 in fibroblasts by HNE treatment is inhibited by the solid-in-oil nanodispersion containing the peptide and HA. The results clearly demonstrate that solid-in-oil nanodispersion containing the HNE inhibitor peptide is a promising strategy for anti-ageing effects. This effect can be seen particularly by ECM regulation by affecting fibroblasts. The formulation also enhances the formation of thicker bundles of actin filaments.

In vitro anti-Candida activity of Glycyrrhiza glabra L.

The severity and frequency of opportunistic fungal infections still growing, concomitantly to the increasing rates of antimicrobial drugs resistance. Natural matrices have been used over years due to its multitude of health benefits, including antifungal potential. Thus, the present work aims to evaluate the anti-Candida potential of the phenolic extract and individual phenolic compounds of Glycyrrhiza glabra L. (licorice), by disc diffusion assay, followed by determination of the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) for both planktonic cells and biofilms. Licorice extract evidenced inhibitory potential against the nineteen tested Candida strains, but no pronounced effect was observed by testing the most abundant individual phenolic compounds. Candida tropicalis strains were the most sensible, followed by Candida glabrata, Candida parapsilosis and, then, Candida albicans. Lower MIC and MFC values were achieved to C. glabrata and C. tropicalis, which confirms its susceptibility to licorice extract; however, for C. tropicalis strains a higher variability was observed. Anti-biofilm potential was also achieved, being most evident in some C. glabrata and C. tropicalis strains. In general, a twice concentration of the MIC was necessary for planktonic cells to obtain a similar potential to that one observed for biofilms. Thus, an upcoming approach for new antifungal agents, more effective and safer than the current ones, is stablished; notwithstanding, further studies are necessary in order to understand its mechanism of action, as also to assess kinetic parameters.

Impact of an educational hands-on project on the antimicrobial, antitumor and anti-inflammatory properties of plants on Portuguese students' awareness, knowledge, and competences

Promoting environmental and health education is crucial to allow students to make conscious decisions based on scientific criteria. The study is based on the outcomes of an Educational Project implemented with Portuguese students and consisted of several activities, exploring pre-existent Scientific Gardens at the School, aiming to investigate the antibacterial, antitumor and anti-inflammatory properties of plant extracts, with posterior incorporation in soaps and creams. A logo and a webpage were also created. The effectiveness of the project was assessed via the application of a questionnaire (pre- and post-test) and observations of the participants in terms of engagement and interaction with all individuals involved in the project. This project increased the knowledge about autochthonous plants and the potential medical properties of the corresponding plant extracts and increased the awareness about the correct design of scientific experiments and the importance of the use of experimental models of disease. The students regarded their experiences as exciting and valuable and believed that the project helped to improve their understanding and increase their interest in these subjects and in science in general. This study emphasizes the importance of raising students’ awareness on the valorization of autochthonous plants and exploitation of their medicinal properties.

Evaluation of antinociceptive and anti-inflammatory activities of the topical preparation of Cipura paludosa (Iridaceae)

Alho do mato (Cipura paludosa, Iridaceae) is a medicinal plant found in the Amazon rain forest, North of Brazil. It has been used to treat algic, inflammatory and infectious processes. The aim of this study was to evaluate the anti-inflammatory and antinociceptive action of the crude Cipura paludosa ethanolic extract at concentrations ranging between 2.0 and 4.0% in Oil and Water cream formulations for topical use. The physical-chemical stability of the formulations was monitored over a six-month period with the use of accelerated stability tests. In order to evaluate the anti-inflammatory and antinociceptive activities, we used a paw edema test induced by carrageenan and a formalin test, respectively. The paw edema test showed that there was a statistical difference in the control group in relation to the treatments. The formalin test did not confirm antinociceptive action of the treatments with the extract in the early phase of the test. However, statistical difference was confirmed for the treatments in relation to the control in the late phase. The antinociceptive and anti-inflammatory activities of Cipura paludosa preparations, as demonstrated in the results, at least partially support the ethno-medical uses of this plant.