Electron transfer complex between nitrous oxide reductase and cytochrome c552 from Pseudomonas nautica: kinetic, nuclear magnetic resonance, and docking studies

Biochemistry. 2008 Oct 14;47(41):10852-62. doi: 10.1021/bi801375q

Structural and electron paramagnetic resonance (EPR) studies of mononuclear molybdenum enzymes from sulfate-reducing bacteria

Acc. Chem. Res., 2006, 39 (10), pp 788–796 DOI: 10.1021/ar050104k

Integrated study by NMR and X-ray Crystallography on the analysis of the molecular interactions in heme-binding proteins

Dissertação para obtenção do Grau de Doutor em Bioquímica, Especialidade Bioquímica Estrutural

Structural and functional studies of PpcA: a key protein in the electron transfer pathways of Geobacter sulfurreducens

Dissertação para obtenção do Grau de Doutor em Bioquímica, ramo de Biotecnologia

Modelling HIV/AIDS length of stay in Portugal

Tese apresentada como requisito parcial para obtenção do grau de Doutor em Estatística e Gestão de Informação pelo Instituto Superior de Estatística e Gestão de Informação da Universidade Nova de Lisboa

Application of ionic liquids and enzymes for the removal of proteinaceous layers from polychrome of works of art and evaluation of the cleaning effectiveness

Dissertação Apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Ciências da Conservação, especialização em Pintura

Homogneous time resolved fluorescence: a new technique for detection and quantifications of infliximab in autoimmune patients

RESUMO:As terapias biológicas revolucionaram o tratamento das doenças autoimunes nos últimos anos. Tipicamente têm como alvos mediadores importantes no mecanismo das doenças. Os antagonistas do fator de necrose tumoral-α (TNF-α) são um grupo de agentes biológicos muito prescrito, pois estão indicados no tratamento de doenças imuno-mediadas comuns, tais como artrite reumatoide, artrite idiopática juvenil, artrite psoriática, espondilite anquilosante, doença de Crohn e colite ulcerosa. Com o uso frequente de inibidores do TNF-α, tem-se tornado evidente que estes agentes têm um potencial imunogénico importante, que pode comprometer o prognóstico a longo prazo dos doentes cronicamente tratados. A produção de anticorpos anti-fármaco parece causar falência terapêutica secundária em muitos doentes. Um dos efeitos dos anticorpos anti-fármaco é o aumento da eliminação do fármaco. A eliminação do fármaco, por sua vez, varia entre indivíduos, refletindo diferentes perfis farmacocinéticos. A determinação dos níveis séricos mínimos do agente anti-TNF-α é assim muito informativa e pode auxiliar nas decisões terapêuticas. Contudo, os testes imunológicos para determinar as concentrações séricas do fármaco não estão facilmente disponíveis na prática clínica. De forma a investigar uma nova técnica potencialmente fidedigna e prática para a deteção e quantificação dos agentes biológicos anti-TNF-α, foi testada a técnica por HTRF (homogeneous time-resolved fluorescence resonance energy transfer) para a determinação de concentrações séricas de infliximab. Apesar de apresentar algumas limitações relacionadas com as condições de leitura da fluorescência, esta técnica provou obter resultados próximos das concentrações obtidas por ELISA (enzyme-linked immunosorbent assay) bridging. Adicionalmente, tem a vantagem de ser de execução muito mais fácil e rápida. Deste modo, a técnica por HTRF poderá ser otimizada e tornar-se uma valiosa ferramenta laboratorial para orientar as decisões terapêuticas em doentes autoimunes com falência da terapêutica anti-TNF-α.--------- ABSTRACT: Biologic therapies revolutionized the treatment of autoimmune diseases in the last years. Typically, they target important disease mediators. Tumor necrosis factor-alpha (TNF-α) antagonists constitute a very prescribed group of biologic agents as they are indicated for the treatment of common immune-mediated diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease and ulcerative colitis. With the increasing use of TNF-α inhibitors it has been noticed that they have an important immunogenic potential that can compromise long-term outcomes in chronically treated patients. The production of anti-drug antibodies seems to cause secondary therapeutic failure in many patients. One of the effects of anti-drug antibodies is the enhancement of drug clearance. Drug clearance, in turn, varies among individuals, reflecting different pharmacokinetic profiles. Determination of serum anti-TNF-α drug trough levels is though very informative and could support treatment decisions. However, immunologic assays to determine drug serum concentrations are not readily available in clinical practice. In order to investigate a potentially reliable and practical new technique for detection and quantification of anti-TNF-α biologic agents, homogeneous time-resolved fluorescence resonance energy transfer (HTRF) technique was tested for determination of serum infliximab concentrations. Although presenting some limitations related with fluorescence reading conditions, this technique proved to give results close to the concentrations obtained by the widely used bridging enzyme-linked immunosorbent assay (ELISA). In addition, it has the advantage of being much easier and faster to perform. Thus, HTRF technique can be optimized and become a valuable laboratorial tool to guide treatment decisions in autoimmune patients with anti-TNF-α therapy failure.

Urban land use and land cover change analysis and modeling a case study area Malatya, Turkey

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Prostate Cancer: The Role of Multiparametric Magnetic Resonance Imaging

Multiparametric Magnetic Resonance Imaging has been increasingly used for detection, localization and staging of prostate cancer over the last years. It combines high-resolution T2 Weighted-Imaging and at least two functional techniques, which include Dynamic Contrast–Enhanced Magnetic Resonance Imaging, Diffusion-Weighted Imaging, and Magnetic Resonance Imaging Spectroscopy. Although the combined use of a pelvic phased-array and an Endorectal Coil is considered the state-of-the-art for Magnetic Resonance Imaging evaluation of prostate cancer, Endorectal Coil is only absolute mandatory for Magnetic Resonance Imaging Spectroscopy at 1.5 T. Sensitivity and specificity levels in cancer detection and localization have been improving with functional technique implementation, compared to T2 Weighted-Imaging alone. It has been particularly useful to evaluate patients with abnormal PSA and negative biopsy. Moreover, the information added by the functional techniques may correlate to cancer aggressiveness and therefore be useful to select patients for focal radiotherapy, prostate sparing surgery, focal ablative therapy and active surveillance. However, more studies are needed to compare the functional techniques and understand the advantages and disadvantages of each one. This article reviews the basic principles of prostatic mp-Magnetic Resonance Imaging, emphasizing its role on detection, staging and active surveillance of prostate cancer.

Custos diretos do tratamento do cancro do cólon no Algarve

RESUMO - O cancro colorretal é um dos tumores mais comuns nos países desenvolvidos e um grave problema de saúde pública. Em Portugal constitui a terceira causa de morte por cancro em ambos os sexos e a segunda para cada sexo separadamente. A sua importância tem vindo a aumentar devido aos custos pessoais e sociais, surgindo internacionalmente como a segunda doença oncológica com os custos económicos mais elevados. No contexto atual, onde os gastos continuam a aumentar e os recursos são limitados, é importante tornar acessível aos decisores políticos o valor dos custos do cancro do cólon, para comparar opções para a prevenção e tratamento desta doença, no momento de afetar os recursos e financiamento do cancro. O objetivo do estudo é medir os custos diretos do tratamento do cancro do cólon na região do Algarve no ano de 2007. Para além da caracterização sociodemográfica e clínica dos doentes, pretende-se relacionar os custos das diferentes tipologias de diagnóstico e tratamento com os estádios da doença, com a idade e com o sexo. Propõe-se um estudo retrospetivo, analítico, transversal, que segue a abordagem custos da doença baseada na prevalência, adotando a perspetiva dos serviços de saúde. A principal fonte dos dados é a plataforma do ROR-Sul, extraindo-se a população constituída por todos os doentes com diagnóstico de cancro do cólon entre 1 de janeiro de 2007 e 31 de dezembro de 2007, residentes no distrito de Faro (n=170). Para a valorização dos custos recorre-se às Portarias que regulam as tabelas de preços dos serviços do Sistema Nacional de Saúde, à contabilidade analítica dos hospitais e ao Infarmed. Os resultados serão analisados através do Statistical Program for Social Sciences (SPSS) versão 20. De forma a verificar a existência de diferenças estatísticas, em termos de médias e da existência de relações, entre as variáveis sociodemográficas e clínicas utilizaram-se vários testes. Consideramos que este estudo será um importante ponto de partida para posteriores análises económicas completas, em termos dos seus custos e suas consequências, nomeadamente a realização da análise custo-efetividade de programas de prevenção primária e secundária do cancro do cólon.

Imaging the Hypoglossal Nerve

The hypoglossal nerve is a pure motor nerve. It provides motor control to the intrinsic and extrinsic tongue muscles thus being essential for normal tongue movement and coordination. In order to design a useful imaging approach and a working differential diagnosis in cases of hypoglossal nerve damage one has to have a good knowledge of the normal anatomy of the nerve trunk and its main branches. A successful imaging evaluation to hypoglossal diseases always requires high resolution studies due to the small size of the structures being studied. MRI is the preferred modality to directly visualize the nerve, while CT is superior in displaying the bony anatomy of the neurovascular foramina of the skull base. Also, while CT is only able to detect nerve pathology by indirect signs, such as bony expansion of the hypoglossal canal, MRI is able to visualize directly the causative pathological process as in the case of small tumors, or infectious/inflammatory processes affecting the nerve. The easiest way to approach the study of the hypoglossal nerve is to divide it in its main segments: intra-axial, cisternal, skull base and extracranial segment, tailoring the imaging technique to each anatomical area while bearing in mind the main disease entities affecting each segment.

Post-Treated Prostate Cancer: Normal Findings and Signs of Local Relapse on Multiparametric Magnetic Resonance Imaging

The use of multiparametric magnetic resonance imaging (mp-MRI) for prostate cancer has increased over recent years, mainly for detection, staging, and active surveillance. However, suspicion of recurrence in the set of biochemical failure is becoming a significant reason for clinicians to request mp-MRI. Radiologists should be able to recognize the normal post-treatment MRI findings. Fibrosis and atrophic remnant seminal vesicles after prostatectomy are often found and must be differentiated from local relapse. Moreover, brachytherapy, external beam radiotherapy, cryosurgery, and hormonal therapy tend to diffusely decrease the signal intensity of the peripheral zone on T2-weighted images (T2WI) due to the loss of water content, consequently mimicking tumor and hemorrhage. The combination of T2WI and functional studies like diffusion-weighted imaging and dynamic contrast-enhanced improves the identification of local relapse. Tumor recurrence tends to restrict on diffusion images and avidly enhances after contrast administration either within or outside the gland. The authors provide a pictorial review of the normal findings and the signs of local tumor relapse after radical prostatectomy, external beam radiotherapy, brachytherapy, cryosurgery, and hormonal therapy.

Economic analysis in health care regulation : three essays

ABSTRACT - It is the purpose of the present thesis to emphasize, through a series of examples, the need and value of appropriate pre-analysis of the impact of health care regulation. Specifically, the thesis presents three papers on the theme of regulation in different aspects of health care provision and financing. The first two consist of economic analyses of the impact of health care regulation and the third comprises the creation of an instrument for supporting economic analysis of health care regulation, namely in the field of evaluation of health care programs. The first paper develops a model of health plan competition and pricing in order to understand the dynamics of health plan entry and exit in the presence of switching costs and alternative health premium payment systems. We build an explicit model of death spirals, in which profitmaximizing competing health plans find it optimal to adopt a pattern of increasing relative prices culminating in health plan exit. We find the steady-state numerical solution for the price sequence and the plan’s optimal length of life through simulation and do some comparative statics. This allows us to show that using risk adjusted premiums and imposing price floors are effective at reducing death spirals and switching costs, while having employees pay a fixed share of the premium enhances death spirals and increases switching costs. Price regulation of pharmaceuticals is one of the cost control measures adopted by the Portuguese government, as in many European countries. When such regulation decreases the products’ real price over time, it may create an incentive for product turnover. Using panel data for the period of 1997 through 2003 on drug packages sold in Portuguese pharmacies, the second paper addresses the question of whether price control policies create an incentive for product withdrawal. Our work builds the product survival literature by accounting for unobservable product characteristics and heterogeneity among consumers when constructing quality, price control and competition indexes. These indexes are then used as covariates in a Cox proportional hazard model. We find that, indeed, price control measures increase the probability of exit, and that such effect is not verified in OTC market where no such price regulation measures exist. We also find quality to have a significant positive impact on product survival. In the third paper, we develop a microsimulation discrete events model (MSDEM) for costeffectiveness analysis of Human Immunodeficiency Virus treatment, simulating individual paths from antiretroviral therapy (ART) initiation to death. Four driving forces determine the course of events: CD4+ cell count, viral load resistance and adherence. A novel feature of the model with respect to the previous MSDEMs is that distributions of time to event depend on individuals’ characteristics and past history. Time to event was modeled using parametric survival analysis. Events modeled include: viral suppression, regimen switch due virological failure, regimen switch due to other reasons, resistance development, hospitalization, AIDS events, and death. Disease progression is structured according to therapy lines and the model is parameterized with cohort Portuguese observational data. An application of the model is presented comparing the cost-effectiveness ART initiation with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus one non-nucleoside reverse transcriptase inhibitor(NNRTI) to two NRTI plus boosted protease inhibitor (PI/r) in HIV- 1 infected individuals. We find 2NRTI+NNRTI to be a dominant strategy. Results predicted by the model reproduce those of the data used for parameterization and are in line with those published in the literature.

Education for sustainable development – How are Portuguese children being educated in order to become responsible consumers

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Pre-treatment of different types of lignocellulosic biomass using ionic liquids

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau Mestre em Biotecnologia