10,968 research outputs found

    Avaliação da eficácia da vacina contra malária placentária em modelo experimental

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    Tese de mestrado em Biologia Evolutiva e do Desenvolvimento, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015A malária é uma doença potencialmente fatal provocada por parasitas do género Plasmodium. Os eritrócitos infetados por Plasmodium exibem antigénios na superfície membranar que se ligam a receptores do endotélio vascular, permitindo a adesão destes eritrócitos infectados a órgãos específicos. Durante a gravidez, as mulheres revelam uma maior suscetibilidade à infecção pelo parasita da malária. Esta suscetibilidade acrescida resulta em consequências negativas tanto para a progenitora como para o(s) neonato(s). Os eritrócitos de mulheres grávidas infectados por Plasmodium falciparum (o mais agressivo dos parasitas do género Plasmodium que infectam humanos) apresentam antigénios na sua superfície que permitem a ligação à placenta, através de recetores aí existentes, como o sulfato de condroitina A (CSA). O CSA interage com VAR2CSA (antigénio presente na superfície de eritrócitos infectados em mulheres grávidas expostas a Plasmodium falciparum). A aquisição natural de anticorpos contra VAR2CSA está associada à ausência de sintomas de malária placentária. Os níveis de anticorpos contra VAR2CSA aumentam ao longo da gravidez e ao longo de sucessivas gravidezes, sendo que mulheres que estiveram grávidas pelo menos uma vez (multigrávidas) são menos vulneráveis à malária placentária do que as que estão grávidas pela primeira vez (primigrávidas). Desta forma, VAR2CSA é um potencial candidato para vacinação contra malária placentária. O principal objetivo deste trabalho foi testar a eficácia da imunização com a sequência extracelular completa de VAR2CSA (recDBL1X-6ε) em fêmeas grávidas de murganho BALB/c infectadas com Plasmodium berghei transgénico, que expressa VAR2CSA. Para isso, as fêmeas foram acompanhadas durante a gravidez e no pós parto e foram analisados os títulos de anticorpos IgG anti-DBL1-6 no seu soro. Os principais resultados deste trabalho mostram que 23% das fêmeas vacinadas com a proteína recDBL1X-6ε foram parcialmente protegidas contra malária placentária, e sugerem que a manutenção de títulos altos de anticorpos IgG1 anti-DBL1X-6ε entre os dias da infeção e do parto possa ser responsável por essa proteção parcial. Também foi observada predominância de IgG1 comparativamente com as subclasses IgG2a e IgG2b, especialmente no pós-parto em mães parcialmente protegidas, o que sugere que pode ser vantajoso apresentar níveis de IgG1 mais altos do que de IgG2a e IgG2b.Malaria is a potentially deadly disease triggered by parasites from the genus Plasmodium. Plasmodium infected erythrocytes exhibit membrane surface antigens which link to vascular endothelium receptors, allowing the adhesion of these infected erythrocytes to specific organs. During pregnancy, women show higher susceptibility to malaria parasite infection, which has negative outcomes for both mother and newborn(s). Pregnant women’s erythrocytes infected by Plasmodium falciparum (the most aggressive among parasites from genus Plasmodium infecting humans) exhibit surface antigens which allow the binding to the placenta through receptors, as chondroitin sulfate A (CSA). CSA interacts with VAR2CSA (an antigen existing on the surface of infected erythrocytes in pregnant women exposed to Plasmodium falciparum). Natural acquisition of antibodies against VAR2CSA is associated to the absence of placental malaria symptoms. Antibody levels against VAR2CSA increase throughout pregnancy and during subsequent pregnancies, and women who were pregnant at least once (multigravid) are less susceptible to placental malaria than the ones who are pregnant for the first time (primigravid). Therefore, VAR2CSA is a potential candidate for vaccination against placental malaria. The main goal of this work was to test the immunization efficacy with full-length extracellular VAR2CSA (recDBL1X-6ε) on BALB/c female pregnant mice infected with transgenic Plasmodium berghei, expressing VAR2CSA. For that purpose, female mice were followed up during pregnancy and in post-delivery, and IgG anti-DBL1-6 antibody titers were analyzed in their sera. The main results of this work show that 23% of female mice vaccinated with recDBL1X-6ε protein were partially protected against placental malaria, and suggest that the maintenance of high IgG1 anti-DBL1X-6ε antibody titers between infection and delivery days can be responsible for that partial protection. It was also observed predominance of IgG1 comparatively to IgG2a and IgG2b subclasses, especially in post-delivery of partially protected mothers, what suggests that can be an advantage having higher levels of IgG1 than IgG2a and IgG2b

    An Incentive-Based Framework for Analyzing the Alignment of Institutional Interventions in the Public Primary Healthcare Sector: The Portuguese Case

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    Over the years, the Portuguese National Health Service has undergone several reforms to face the challenges posed by internal and external factors on the access to and quality of its health services. One of its most recent reforms addressed the primary healthcare sector, where understanding the incentives behind the actors of the inherent institutional interventions and how they are aligned with the governing health policies is paramount for reformative success. With the purpose of acknowledging the alignment of the primary healthcare sector’s institutional interventions from an incentive-based perspective, we propose a framework resting on a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis, which was built in cooperation with a panel of decision-making actors from the Portuguese Ministry of Health. In the end, we derive possible policy implications and strategies. This holistic approach highlighted the positive impact of the primary healthcare reform in the upgrade of physical resources and human capital but stressed the geosocial asymmetries and the lack of intra- and inter-sectorial coordination. The proposed framework serves also as a guideline for future primary healthcare reforms, both national- and internationally.info:eu-repo/semantics/publishedVersio

    Multifocalidade e Estereopsia

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    Introdução: A visão binocular proporciona uma interpretação única e tridimensional do mundo. Objectivo: Comparar a estereopsia dos doentes com de lentes intra-oculares (LIO) multifocais implantadas. Métodos: Os autores realizaram um estudo transversal com 40 doentes, que tinham sido submetidos a facoemulsificação com implante de LIO multifocal bilateralmente (26 Restor, 6 tecnis Multifocal e 8 "Mix & Match"). Estudaram a estereopsia de longe com o Vectograph e utilizaram o "Titmus Stereo Test" para perto, nos 3 grupos. Resultados: No grupo 1 (Restor bilateral: idade média 63,38 anos; 4 doentes do sexo masculino e 22 do feminino) obtivemos 80 a 90% de boa estereopsia; no grupo 2 (Tecnis Multifocal bilateral: idade média 73,67 anos; 6 doentes do sexo feminino) registou-se 100% de boa estereopsia e no grupo 3 ("Mix & Match": idade média 74,25 anos; 2 doentes do sexo masculino e 6 do feminino) obteve-se 50 a 75% de boa estereopsia. Conclusões: Os doentes com lentes intra-oculares multifocais similares implantadas bilateralmente obtiveram melhor estereopsia para perto e para longe

    An iron giant with feet of clay? in the midst of the steelmaking transition strategy

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    This report contains a detailed analysis of the Vale S.A. Ferrous Minerals operations, including a deep dive into the global iron ore demand under future steelmaking scenarios. Finally, an analysis of the main value drivers is performed, providing the necessary assumptions for the forecasts of the segment’s revenues and costs upon which its valuation is performed

    Perylene Diimide acceptors: Fabrication and characterization of electron-only, hole-only devices and solar cells

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    The thrust towards energy conservation and reduced environmental footprint has fueled intensive research for alternative low cost sources of renewable energy. Organic photovoltaic cells (OPVs), with their low fabrication costs, easy processing and flexibility, represent a possible viable alternative. Perylene diimides (PDIs) are promising electron-acceptor candidates for bulk heterojunction (BHJ) OPVs, as they combine higher absorption and stability with tunable material properties, such as solubility and position of the lowest unoccupied molecular orbital (LUMO) level. A prerequisite for trap free electron transport is for the LUMO to be located at a level deeper than 3.7 eV since electron trapping in organic semiconductors is universal and dominated by a trap level located at 3.6 eV. Although the mostly used fullerene acceptors in polymer:fullerene solar cells feature trap-free electron transport, low optical absorption of fullerene derivatives limits maximum attainable efficiency. In this thesis, we try to get a better understanding of the electronic properties of PDIs, with a focus on charge carrier transport characteristics and the effect of different processing conditions such as annealing temperature and top contact (cathode) material. We report on a commercially available PDI and three PDI derivatives as acceptor materials, and its blends with MEH-PPV (Poly[2-methoxy 5-(2-ethylhexyloxy)-1,4-phenylenevinylene]) and P3HT (Poly(3-hexylthiophene-2,5-diyl)) donor materials in single carrier devices (electron-only and hole-only) and in solar cells. Space-charge limited current measurements and modelling of temperature dependent J-V characteristics confirmed that the electron transport is essentially trap-free in such materials. Different blend ratios of P3HT:PDI-1 (1:1) and (1:3) show increase in the device performance with increasing PDI-1 ratio. Furthermore, thermal annealing of the devices have a significant effect in the solar cells that decreases open-circuit voltage (Voc) and fill factor FF, but increases short-circuit current (Jsc) and overall device performance. Morphological studies show that over-aggregation in traditional donor:PDI blend systems is still a big problem, which hinders charge carrier transport and performance in solar cells
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