Prevalence of neurocognitive disorders and depression in a Brazilian HIV population

AbstractINTRODUCTION:Combined antiretroviral therapy has enabled human immunodeficiency virus (HIV) carriers to live longer. This increased life expectancy is associated with the occurrence of degenerative diseases, including HIV-associated neurocognitive disorders (HAND), which are diagnosed via a complex neuropsychological assessment. The International HIV Dementia Scale (IHDS) is a screening instrument validated in Brazil for use in the absence of neuropsychological evaluation. HIV patients are frequently diagnosed with depression. We aimed to determine the prevalence of neurocognitive impairment using the IHDS and depressive disorders using the Hamilton Rating Scale for Depression (HAM-D17), compare the IHDS performance with the performances on the Timed Gait Test (TGT), the Digit Symbol Coding Test (DS) and the Brazilian version of the Scale of Instrumental Activities of Daily Living (IADL), and evaluate the association between the IHDS performance and clinical-demographic variables.METHODS:One hundred fourteen patients were evaluated in a cross-sectional study conducted in a public outpatient clinic for infectious diseases in Marília City, State of São Paulo, Brazil. Data were collected following consultation. Statistical analysis was performed in accordance with the nature and distribution of the data and hypotheses.RESULTS:According to the IHDS, 53.2% of the sampled patients were neuropsychologically impaired. According to the HAM-D17, 26.3% had depressive disorders. There were significant associations between the IHDS and the TGT and DS. Multiple regression analysis indicated that female gender, educational level, and cluster of differentiation 4 (CD4) levels were significantly and independently associated with neurocognitive impairment.CONCLUSIONS:The prevalence of neurocognitive impairment according to the IHDS is high and associated with female gender, education level, and low CD4 levels.

Analysis of world economic variables using multidimensional scaling

Waves of globalization reflect the historical technical progress and modern economic growth. The dynamics of this process are here approached using the multidimensional scaling (MDS) methodology to analyze the evolution of GDP per capita, international trade openness, life expectancy, and education tertiary enrollment in 14 countries. MDS provides the appropriate theoretical concepts and the exact mathematical tools to describe the joint evolution of these indicators of economic growth, globalization, welfare and human development of the world economy from 1977 up to 2012. The polarization dance of countries enlightens the convergence paths, potential warfare and present-day rivalries in the global geopolitical scene.

Development of human central nervous system 3D in vitro models for preclinical research

Neurological disorders are a major concern in modern societies, with increasing prevalence mainly related with the higher life expectancy. Most of the current available therapeutic options can only control and ameliorate the patients’ symptoms, often be-coming refractory over time. Therapeutic breakthroughs and advances have been hampered by the lack of accurate central nervous system (CNS) models. The develop-ment of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of novel therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmentally, anatomically and physiologically) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity). The in vitro recapitulation of CNS phenotypic and functional features requires the implementation of advanced culture strategies that enable to mimic the in vivo struc-tural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. This thesis aimed at the development of novel human 3D in vitro CNS models by integrat-ing agitation-based culture systems and a wide array of characterization tools. Neural differentiation of hNSC as 3D neurospheres was explored in Chapter 2. Here, it was demonstrated that human midbrain-derived neural progenitor cells from fetal origin (hmNPC) can generate complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. Chapter 3 focused on the development of cellular characterization assays for cell aggregates based on light-sheet fluorescence imaging systems, which resulted in increased spatial resolu-tion both for fixed samples or live imaging. The applicability of the developed human 3D cell model for preclinical research was explored in Chapter 4, evaluating the poten-tial of a viral vector candidate for gene therapy. The efficacy and safety of helper-dependent CAV-2 (hd-CAV-2) for gene delivery in human neurons was evaluated, demonstrating increased neuronal tropism, efficient transgene expression and minimal toxicity. The potential of human 3D in vitro CNS models to mimic brain functions was further addressed in Chapter 5. Exploring the use of 13C-labeled substrates and Nucle-ar Magnetic Resonance (NMR) spectroscopy tools, neural metabolic signatures were evaluated showing lineage-specific metabolic specialization and establishment of neu-ron-astrocytic shuttles upon differentiation. Chapter 6 focused on transferring the knowledge and strategies described in the previous chapters for the implementation of a scalable and robust process for the 3D differentiation of hNSC derived from human induced pluripotent stem cells (hiPSC). Here, software-controlled perfusion stirred-tank bioreactors were used as technological system to sustain cell aggregation and dif-ferentiation. The work developed in this thesis provides practical and versatile new in vitro ap-proaches to model the human brain. Furthermore, the culture strategies described herein can be further extended to other sources of neural phenotypes, including pa-tient-derived hiPSC. The combination of this 3D culture strategy with the implemented characterization methods represents a powerful complementary tool applicable in the drug discovery, toxicology and disease modeling.

Desenvolvimento e caracterização tribológica de hidrogéis poliméricos de PVA reforçados com fosfato tricálcico para aplicação como cartilagem articular para implantes articulares

Dissertação de mestrado integrado em Engenharia de Materiais

Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

Biochemical and physical surface functionalization of polycaprolactone as a key mediator of osteogenic differentiation and vascularized tissue morphogenesis

Tese de Doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células Estaminais.

Re-Design of ribbon for new applications

O conceito de qualidade de vida surge pela primeira vez em 1920, através do economista inglês Arthur Cecil Pigou, que utiliza este termo para descrever o impacto governamental sobre a vida das pessoas mais desfavorecidas. Com a instalação de uma era industrializada e com o fim da 2º Guerra Mundial, a sociedade mudou de paradigma e iniciou uma procura incessante de formas para melhorar a sua qualidade de vida. Este conceito desenvolve-se juntamente com o desenvolvimento do conceito de educação, saúde, habitação, transporte, trabalho e lazer, bem como indicadores do aumento da esperança de vida, a diminuição da mortalidade infantil e dos níveis de poluição. O avanço da tecnologia teve um papel fundamental para a evolução desses conceitos, bem como o Design na procura de soluções para aplicação dessas mesmas tecnologias. No caso concreto da indústria tèxtil, a tendência é o desenvolvimento de têxteis inteligentes envolvendo a engenharia electrónica no seu processo de conceptualização e de fabrico. A chamada tecnologia wearable abre novos horizontes para a criação de soluções inovadoras, abrindo novos nichos de mercado com elevado valor acrescentado. Existem atualmente vários produtos no mercado cuja funcionalidade e utilidade lhes conferiu um estatuto imutável ao longo dos anos, onde a evolução não avançou na tendência atual. Esse é o caso dos tecidos estreitos, cuja funcionalidade poderá adquirir novas capacidades e ser utilizada em diferentes componentes têxteis nas mais variadas áreas. Essas capacidades poderão ser acrescentadas pela incorporação de materiais com luminosidade (Led’s e L-Wire) nas suas estruturas. Neste estudo realizado o design de produtos com novas funcionalidades, adaptando as tecnologias até agora desenvolvidas em novas soluções e/ou novas recriações de produto.

Envelhecimento, memória e estímulo cognitivo

Neste artigo apresentamos uma breve revisão da literatura sobre o papel da memória no processo de envelhecimento e a deterioração que esta sofre em caso de demência, por exemplo de Alzheimer. Expomos ainda um ensaio/programa de treino cognitivo para estimular/reabilitar a memória. O aumento acentuado da esperança de vida, associado à baixa natalidade que se vem observando na maioria dos países ocidentais, poderá fazer com que as manifestações psicopatológicas da terceira idade se tornem bastante incidentes. Torna-se portanto indispensável que o envelhecimento decorra de forma natural, saudável, simplificando o funcionamento do organismo e libertando-o de problemas indesejáveis. Com o presente artigo procuramos alertar a comunidade para o tema do envelhecimento, da consequente diminuição de capacidades cognitivas, funcionais e executivas, fazendo um especial enfoque à memória.

Desenvolvimento de rede neuronal artificial para o diagnóstico de doenças neurodegenerativas

Dissertação de mestrado integrado em Engenharia Eletrónica Industrial e Computadores

In vivo antioxidant activity of phenolic compounds: facts and gaps

Background: Numerous diseases have been related with free radicals overproduction and oxidative stress. Botanical preparations possess a multitude of bioactive properties, including antioxidant potential, which has been mainly related with the presence of phenolic compounds. However, the mechanisms of action of these phytochemicals, in vivo effects, bioavailability and bio-efficacy still need research. Scope and Approach: The present report aims to provide a critical review on the aspects related with the in vivo antioxidant activity of phenolic extracts and compounds from plant origin. Key findings: Biological functions beyond the human metabolism were discussed, comparing in vivo vs. in vitro studies, as also focusing the conditioning factors for phenolic compounds bioavailability and bio-efficacy. Furthermore, an upcoming perspective about the use of phytochemicals as life expectancy promoters and anti-aging factors in human individuals was provided. Conclusions: Overall, and despite all of those advances, the study of the biological potential of numerous natural matrices still remains a hot topic among the scientific community. In fact, the available knowledge about the responsible phytochemicals for the biological potential, their mechanisms of action, the establishment of therapeutic and prophylactic doses, and even the occurrence of biochemical inter-relations, is considerable scarce.

O setor de distribuição farmacêutica em Portugal estrutura e estratégias

A presente investigação desenvolveu uma análise profunda do setor da distribuição farmacêutica, no período compreendido entre 2000 e 2009, procurando identificar as possíveis relações de interdependência entre o meio envolvente e as opções de estratégia das empresas que constituíram a amostra de estudo e entre as referidas opções de estratégia e as estruturas e o desempenho dessas empresas. A dinâmica do mercado do medicamento na economia nacional, com um valor de 3,2 mil milhões de euros anuais (Infarmed, 2010), apresenta um impacto significativo na esperança de vida e na qualidade de vida dos cidadãos. Segundo a OCDE, os produtos farmacêuticos são responsáveis por quase um quinto de todos os gastos com saúde, em média, nos países da OCDE. Neste contexto, a distribuição farmacêutica representa uma componente crítica. A disponibilização de medicamentos em ambulatório num curto espaço de tempo só é possível devido a uma estrutura logística com características muito específicas. A qualidade do armazenamento e do transporte dos medicamentos desde a saída dos laboratórios até à chegada às farmácias é rigorosamente monitorizada e controlada. O setor da distribuição farmacêutica assume assim uma postura elementar na cadeia do medicamento, contribuindo para a melhoria da qualidade do sistema de saúde que se tem vindo a verificar nas últimas décadas e prestando um serviço com valor para a comunidade, uma vez que se compromete a assegurar um adequado e contínuo fornecimento de medicamentos para que as necessidades dos doentes e das populações em geral sejam satisfeitas. As alterações verificadas ao longo dos últimos anos estimularam a dinâmica concorrencial entre os diferentes agentes neste mercado, bastante regulamentado e com elevado entrosamento financeiro com o Estado, o que obrigou a rápidas mudanças. Neste contexto, a sobrevivência das empresas, o seu crescimento e a sua perenidade futura têm constituído um desafio abordado de forma diversa por cada empresa.

Development of procedures for the design, optimization and manufacturing of customized orthopaedic and trauma implants: Geometrical/anatomical modelling from 3D medical imaging

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

O direito fundamental à proteção na velhice através dos impostos

Dissertação de mestrado em Direito das Crianças, Família e Sucessões

Relatório de atividade profissional

Relatório de atividade profissional de mestrado em Ciências – Formação Contínua de Professores (área de especialização em Matemática)

Mechanical versus biological aortic valve implants in the elderly. A comparison of early and mid-term results

OBJECTIVE: Our aim was to compare, in a non randomized study, the surgical outcome in elderly patients with mechanical (Group 1; n=83) and bioprosthetic valve implants (Group 2; n=136). METHODS: During a three year period, 219 patients >75 years underwent Aortic Valve Replacement. The groups matched according to age, sex, comorbidity, valve pathology and concomitant Coronary Artery Bypass Surgery. Follow-up was a total of 469 patient-years (mean follow-up 2.1 years, maximum 4,4 years). RESULTS: Operative mortality was zero and the overall early mortality was 2.3 % (within 30 days). Actuarial survival was 87.5 ± 4.0% and 66.1 ± 7.7% (NS) at 4 years in Group 1 and Group 2, respectively. Freedom from valve-related death was 88.9 ± 3.8% in Group 1 and 69.9±7.9% (NS) in Group 2 at 4 years. CONCLUSION: Aortic Valve Replacement in the elderly (>75 years) is a safe procedure even in cases where concomitant coronary artery revascularization is performed. Only a few anticoagulant-related complications were reported and this may indicate that selected groups of elderly patients with significant life expectancy may benefit from mechanical implants .