Modulation of α-synuclein aggregation and toxicity

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Mental health care assessed based on structure, process and outcome : a retrospective cohort study

RESUMO: As doenças mentais são comuns, universais e associadas a uma significativa sobrecarga pessoal, familiar, social e económica. Os Serviços de Saúde Mental devem abordar de forma adequada as necessidades dos pacientes e familiares tanto ao nível clínico como também ao nível social. O presente estudo foi realizado num período de grande transformação nos sistemas de saúde primário e de saúde mental em Portugal, num Departamento de Psiquiatria desenvolvido com base nos princípios da OMS. Os objectivos incluem a caracterização: 1) das Unidades Funcionais do Departamento; 2) dos pacientes internados pela primeira vez no internamento de agudos; 3) da utilização dos serviços nas equipas comunitárias após a alta; e 4) da avaliação de alguns dos indicadores de qualidade do departamento, com recurso ao modelo de Donabedian sobre a articulação entre a Estrutura-Processo-Resultados. Metodologia: Foi escolhido um estudo de coorte retrospectivo. Todos os pacientes internados pela primeira vez entre 2008 e 2010 foram incluídos no estudo. Os seus processos clínicos e a base de dados do hospital onde são registados todos os contactos que estes tiveram com os profissionais de saúde mental foram revistos de forma a obter dados sociodemográficos e clínicos, durante o período do estudo e após a alta. Os instrumentos utilizados foram o WHO-ICMHC (Classificação Internacional de Cuidados de Saúde Mental), para caracterizar o Departamento, o AIESMP (Avaliação Inicial de Enfermagem em Saúde Mental e Psiquiatria) para recolha dos dados sociodemográficos, e o VSSS (Escala de Satisfação com os Serviços de Verona) de forma a avaliar a satisfação dos pacientes em relação aos cuidados recebidos. A análise estatística incluiu a análise descritiva, quantitativa e qualitativa dos dados. Resultados: As Unidades Funcionais do Departamento revelaram níveis elevados de articulação e consistência com as necessidades de cuidados psiquiátricos e reabilitação psicossocial dos pacientes. Os 543 pacientes admitidos pela primeira vez eram maioritariamente (56.9%) mulheres, caucasianas (81.2%), com diagnóstico de perturbações do humor (66.3%), internadas voluntariamente (59.7%), e uma idade média de 45.1 anos. Estas eram significativamente mais velhas, mais frequentemente empregadas, casadas/coabitar e tinham uma prevalência mais elevada de perturbações do humor, comparativamente aos homens. O internamento compulsivo era mais significativo nos homens (54.7%). A taxa de abandono no pós-alta (4.2%) e a taxa de reinternamentos (2.9%) na quinzena após a alta revelaram-se inferiores aos padrões na literatura internacional. De forma global, a satisfação dos pacientes com os cuidados de saúde mental foi positiva. Conclusões: Os cuidados prestados mostraram-se eficazes, adaptados e baseados nas necessidades e problemas específicos dos pacientes. A continuidade e a abrangência de cuidados foram difundidos e mantidos ao longo do processo de cuidados. Este Departamento pode ser considerado um exemplo de como proporcionar tratamento digno e eficiente, e uma referência para futuros serviços de psiquiatria.-------------- ABSTRACT: Mental health disorders are common, universal, and associated with heavy personal, family, social and economic burden. Mental health services should be aimed at adequately addressing patients’ and families’ needs at clinical and social level. The current study was carried out at a time of great transformation in the health and mental health systems in Portugal, in a Psychiatric Department developed taking in consideration the WHO principles. The objectives included characterizing: 1) the Psychiatric Department’s different units; 2) the patients admitted for the first time to the inpatient unit; 3) their use of community mental health services after discharge; and 4) assessing some of the department’s quality indicators, with resource to Donabedian’s Structure-Process-Outcome model. Methodology: A retrospective cohort design was chosen. All the firstly admitted patients in the period between 2008 and 2010 were included in the study. Their clinical records and the hospital’s database which registers all of the contacts the patients had with the mental health professionals during the study period, were reviewed to retrieve sociodemographic and clinical data and information on follow-up. The instruments used were the WHO International Classification of Mental Health Care (ICMHC) to characterize the department, the Initial Nurses’ Assessment in Mental Health and Psychiatry (AIESMP) for patients’ sociodemographic data, and the Verona Service Satisfaction Scale (VSSS) to assess patients’ satisfaction with care received. Statistical analysis included descriptive, quantitative and qualitative analysis of the data. Results: The Department’s Functional units revealed high levels of articulation, and were consistent with patients’ needs for psychiatric care and psychosocial rehabilitation. The 543 patients firstly admitted were mainly (56.9%) female, Caucasian (81.2%), diagnosed with mood disorders (66.3%), voluntarily admitted (59.7%), and with a mean age of 45.1 years. Female patients were significantly older, more frequently employed, married/cohabiting and had a higher prevalence of mood disorders when compared to males. Involuntary admission was more significant in males (54.7%). Dropout rates during follow-up (4.2%) and readmission rates (2.9%) in the fortnight following discharge were lower than standards in international literature. Overall patients’ satisfaction with mental health care was positive. Conclusions: The care delivered was effective, adapted and based on the patients’ specific needs and problems. Continuity and comprehensiveness of care was endorsed and maintained throughout the care process. This department may be considered an example of both humane and effective treatment, and a reference for future psychiatric care.

Clonal structure of Trypanosoma cruzi Colombian strain (biodeme Type III): biological, isoenzymic and histopathological analysis of seven isolated clones

The clonal structure of the Colombian strain of Trypanosoma cruzi, biodeme Type III and zymodeme 1, was analyzed in order to characterize its populations and to establish its homogeneity or heterogeneity. Seven isolated clones presented the basic characteristics of Biodeme Type III, with the same patterns of parasitemic curves, tissue tropism to skeletal muscle and myocardium, high pathogenicity with extensive necrotic-inflammatory lesions from the 20th to 30th day of infection. The parental strain and its clones C1, C3, C4 and C6, determined the higher levels of parasitemia, 20 to 30 days of infection, with high mortality rate up to 30 days (79 to 100%); clones C2, C5 and C7 presented lower levels of parasitemia, with low mortality rates (7.6 to 23%). Isoenzymic patterns, characteristic of zymodeme 1, (Z1) were similar for the parental strain and its seven clones. Results point to a phenotypic homogeneity of the clones isolated from the Colombian strain and suggest the predominance of a principal clone, responsible for the biological behavior of the parental strain and clones.

The impact of changing the transportation cost structure of a food retail company

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

Italian interlocking directorates: structure, evolution and cross-country comparisons

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

STRUCTURE-FUNCTION ANALYSIS OF MULTI-COPPER OXIDASES

Dissertation presented to obtain the Ph.D degree in Biochemistry, Structural Biochemistry

Ageing on commercial automotive catalysts, a structure reactivity study

Increasingly stringed regulations for diesel engine emissions have a significant impact on the required efficiency of DOC. Lowered DOC oxidation efficiency due to thermal aging effects influences the efficiency of the exhaust aftertreatment systems downstream of the DOC. In this work carried out in the Jean Le Rond d’Alembert Institute the effect of hydrothermal aging on the reactivity and structure of a commercial DOC was investigated. The characterization of the catalytic performance was carried out on a synthetic gas bench using carrots catalyst under conditions close to the realistic conditions i.e. using a synthetic gas mixture, representative of the exhaust gases from diesel engines. Different structural characterization techniques were performed: textural and morphological proprieties were analyzed by BET and TEM, the characterization of the presented crystallographic phases was performed by DRX and the determination of the number of reducible species was possible by TPR. TEM results shown, an increase of the metal particle size with the aging caused by the agglomeration of metal particles, revealing the presence of metal sintering. DRX results also suggest the presence of support sintering. Furthermore, DRX and BET results unexpectedly reveal that the most drastic aging conditions used actually activated the catalyst surface. As expected, the aging affected negatively the catalyst performance on the oxidation of methane and CO, however an improvement of the NO oxidation performance with the aging was observed. Nevertheless, for the aging conditions used, catalytic activity results show that the influence of aging in DOC performance was not significant, and therefore, more drastic aging conditions must be used.

UAV - based imagery processing using structure from motion and remote sensing technology

With the recent advances in technology and miniaturization of devices such as GPS or IMU, Unmanned Aerial Vehicles became a feasible platform for a Remote Sensing applications. The use of UAVs compared to the conventional aerial platforms provides a set of advantages such as higher spatial resolution of the derived products. UAV - based imagery obtained by a user grade cameras introduces a set of problems which have to be solved, e. g. rotational or angular differences or unknown or insufficiently precise IO and EO camera parameters. In this work, UAV - based imagery of RGB and CIR type was processed using two different workflows based on PhotoScan and VisualSfM software solutions resulting in the DSM and orthophoto products. Feature detection and matching parameters influence on the result quality as well as a processing time was examined and the optimal parameter setup was presented. Products of the both workflows were compared in terms of a quality and a spatial accuracy. Both workflows were compared by presenting the processing times and quality of the results. Finally, the obtained products were used in order to demonstrate vegetation classification. Contribution of the IHS transformations was examined with respect to the classification accuracy.

Modulation of electrical stimulation applied to human physiology and clinical diagnostic

The use, manipulation and application of electrical currents, as a controlled interference mechanism in the human body system, is currently a strong source of motivation to researchers in areas such as clinical, sports, neuroscience, amongst others. In electrical stimulation (ES), the current applied to tissue is traditionally controlled concerning stimulation amplitude, frequency and pulse-width. The main drawbacks of the transcutaneous ES are the rapid fatigue induction and the high discomfort induced by the non-selective activation of nervous fibers. There are, however, electrophysiological parameters whose response, like the response to different stimulation waveforms, polarity or a personalized charge control, is still unknown. The study of the following questions is of great importance: What is the physiological effect of the electric pulse parametrization concerning charge, waveform and polarity? Does the effect change with the clinical condition of the subjects? The parametrization influence on muscle recruitment can retard fatigue onset? Can parametrization enable fiber selectivity, optimizing the motor fibers recruitment rather than the nervous fibers, reducing contraction discomfort? Current hardware solutions lack flexibility at the level of stimulation control and physiological response assessment. To answer these questions, a miniaturized, portable and wireless controlled device with ES functions and full integration with a generic biosignals acquisition platform has been created. Hardware was also developed to provide complete freedom for controlling the applied current with respect to the waveform, polarity, frequency, amplitude, pulse-width and duration. The impact of the methodologies developed is successfully applied and evaluated in the contexts of fundamental electrophysiology, psycho-motor rehabilitation and neuromuscular disorders diagnosis. This PhD project was carried out in the Physics Department of Faculty of Sciences and Technology (FCT-UNL), in straight collaboration with PLUX - Wireless Biosignals S.A. company and co-funded by the Foundation for Science and Technology.

How do current term structure model behave beyond the last liquid point?: A comparison of the DNS and Smith-Wilson methods

A Work Project, presented as part of the requirements for the Award of a Master’s Double Degree in Finance from Maastricht University and NOVA – School of Business and Economics

Design and characterization of novel biopolymeric structure using biocompatible ionic liquids

The main objective of this thesis was the development of polymeric structures from the dissolution of FucoPol, a bacterial exopolysaccharide (EPS), in a biocompatible ionic liquid, choline acetate. The FucoPol was produced by the bacteria Enterobacter A47 using glycerol as carbon source at controlled temperature and pH (30ºC and 7, respectively). At the end of 3 days it was produced 7 g/L of FucoPol. The net yield of Fucopol in glycerol (YP/S) was 0.22 g/g and the maximum productivity 2.37 g/L.d This polymer was characterized about its composition in sugars and acyl groups (by High-Performance Liquid Chromatography - HPLC), containing fucose (35 % mol), galactose (21 % mol), glucose (29 % mol), rhamnose (3% mol) and glucuronic acid (12% mol) as well as acetate (14.28 % mol), pyruvate (2.15 % mol) and succinate (1.80 % mol). Its content of water and ash was 15% p/p and 2% p/p, respectively, and the chemical bonds (determined by Infrared Spectroscopy - FT-IR) are consistent to the literature reports. However, due to limitations in Differential Scanning Calorimetry (DSC) equipment it was not possible to determine the glass transition temperature. In turn, the ionic liquid showed the typical behavior of a Newtonian fluid, glass transition temperature (determined by DSC) -98.03ºC and density 1.1031 g/cm3. The study of chemical bonds by FT-IR showed that amount of water (8.80%) influenced the visualization of the bands predicted to in view of their chemical structure. After the dissolution of the FucoPol in the ionic liquid at different temperatures (50, 60, 80 and 100 ° C) it was promoted the removal of this by the phase inversion method using deionized water as a solvent, followed by drying in an oven at 70 ° C. The mixtures before and after the phase inversion method were characterized through the studies mentioned above. In order to explore possible application field’s biocompatibility assays and collage on balsa wood tests were performed. It was found that the process of washing with water by the phase inversion method was not totally effective in removing the biocompatible ionic liquid, since all FucoPol – IL mixtures still contained ionic liquid in their composition as can be seen by the DSC results and FT-IR. In addition, washing the mixtures with water significantly altered the composition of FucoPol. However, these mixtures, that developed a viscous behavior typical of a non-Newtonian fluid (shear-thinning), have the potential to be applied in the biomedical field as well as biological glues.

Does ownership structure matter? Three essays in finance

Management

The Multidimensional and Centred Structure of Our Interested Perception in Hierocles

O objectivo desta dissertação é identificar a estrutura da percepção tal como ela é desenhada por Hiérocles nos <,(#= >1!(?$%&'(). Para alcançar este objectivo focar-me-ei na análise que o filósofo estóico leva a cabo em torno da percepção. O foco começa por incindir sobre a distinção entre percepção de si e percepção do exterior, com todas as suas subtilezas. Tal análise implicará então a consideração da importância da não-indiferença nessa estrutura de percepção. O objectivo é compreender como a percepção é sempre relacional e interessada. . Centrar-me-ei então na noção de !"#$%&'(), tentanto explorar a complexidade e multiplicidade do fenómeno em causa. Será também estabalecida a relação com o fragmento de Estobeu (6.671), que é, a par da obra, a fonte mais importante do pensamento de Hiérocles. Através desta relação introduzir-se-á a estrutura circular e concêntrica de uma percepção relacional e interessada. Toda esta dissertação será levada a cabo focando-se principalmente nos textos do próprio Hiérocles.

Inovcity- Structure of trials evaluation

In 2007, the UK government commissioned the Energy Demand Research Project to conduct a large scale experiment of smart metering technologies to test the impacts from many different forms of feedback to residential consumers. A full evaluation of the results was completed in 2011. In Portugal, EDP is also conducting smart meter trials in a project called InovCity in the city of Évora whose results will be evaluated during 2012. In this work, the case of Great Britain is studied as a reference on how an evaluation of trial results should be conducted. I also discuss potential limitations of the experiments, implications for national roll-out decisions, and finally draw some lessons that can be applied to the Portuguese case.

The role of Hedgehog signaling during zebrafish larvae fin fold regeneration

Several studies have demonstrated that although the structure of the adult and larval zebrafish caudal fin is different, there are similarities at the cellular and molecular level that turn larval zebrafish fin fold a useful model to study the basic principles of regeneration. In this process, while the essential role for Hedgehog (Hh) signaling is well established in the adult zebrafish caudal fin system, its involvement in juvenile tissue regeneration is still unknown. The aim of this Master thesis was therefore to evaluate the contribution of the Hh signaling pathway to the larval zebrafish fin fold regeneration process. Accordingly, we analyzed the expression of several Hh signaling components through in situ hybridization. Here, we showed that several of these genes are effectively expressed in the larval regenerating fin tissue, suggesting a role for Hh signaling also during larval regeneration. However, divergence in the regulation of few Hh signaling components appears to exist between the adult and larval zebrafish fin regeneration processes. Nevertheless, similarly to adult caudal fin regeneration, when Hh signaling was blocked, by using cyclopamine, the larval fin fold regenerative outgrowth is severely impaired. Since larval zebrafish fin fold is ciliated, and primary cilia are closely related to Hh signaling regulation in vertebrate systems, we further addressed the role of primary cilia during larval fin fold regeneration process. To this end, we used the zebrafish iguana mutant, in which primary cilia are not formed, to study the modulation of Hh signaling expression during larval fin fold regeneration in the absence of primary cilia. Here, we found that several genes were expressed with a delay, coincident with the delay in the mutant fin fold regeneration observed in previous work. We show that Hh signaling in the fin fold is crucial to promote cell proliferation. When Hh signaling is blocked using cyclopamine there is a strong blockage of cell proliferation and regeneration is also blocked. Surprisingly, in iguana mutants where Hh signaling is impaired but not totally blocked, cell proliferation is not detected but regeneration still occurs. This raises the question about the requirement of cell proliferation in larvae fin fold regeneration. By blocking the cell cycle using aphidicolin we demonstrate that cell proliferation is not necessary for zebrafish larvae fin fold regeneration.