Henoch-Schönlein Purpura Associated with Pulmonary Adenocarcinoma

Introduction: The Henoch-Schönlein purpura (HSP) is an immunoglobulin A (IgA)-mediated smallvessel systemic vasculitis, rare in adults. The association with solid tumours has been described, especially with lung cancer. Case Report: We present the case of a 60-year-old Caucasian male, diagnosed with lung adenocarcinoma that underwent surgical resection without (neo)adjuvant theraphy. Two months latter he was admitted for abdominal pain, purpuric rash on his lower extremities and acute kidney injury, with serum creatinine (Scr) of 2 mg/dl. Urinalysis revealed haematuria and 24h proteinuria (P24h) of 1.5 g. The serum protein electrophoresis, complement components C3 and C4, circulating immune complexes, cryoglobulins, ANCA, ANA, anti-dsDNA and the remaining immunologic study as screening for viral infections (HCV, HBV and HIV) were negative. Renal ultrasound was normal and kidney biopsy revealed mild mesangial proliferation; 2 cellular glomerular crescents and 1 fibrinoid necrosis lesion; large amounts of red blood cell casts; lymphocytic infiltration in the intertubular interstitial capillaries; moderate arteriolar hyalinosis. Immunofluorescence demonstrated mesangial and parietal deposits of IgA. The diagnosis of HSP was assumed, and the patient started prednisolone 1 mg/kg/day. Ten months after diagnosis the patient’s baseline Scr is 1.4 mg/dl with P24h of 0.18g, without haematuria. Conclusion: Although this is a rare association and the exact mechanism behind the disease is yet unknown, physicians should be aware of it. The early recognition and treatment may prevent renal disease progression.

The design and use of annual budgets to cope with uncertainty

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

Acute Otitis Media a Reliable Warning Sign for Primary Immunodeficiencies?- A Critical Appraisal

Acute otitis media (AOM) is the most common infection in childhood, resulting from both anatomic and immunologic specificities of this age group. Recurrent AOM has been defined as one of the warning signs for primary immunodeficiencies (PID), In this study we evaluated the strength of recurrent AOM as clinical predictor of PID. Methods: Retrospective study (August 2010 - December 2013) which included all patients referred to PID appointment because of recurrent AOM (= 8 AOM episodes/year). Syndromic patients or those presenting with another warning sign for PID were excluded. Clinical, demographic and laboratory results were analized and statistical analysis was made using SPSS 20. Results: Seventy-five patients were included (median age 37,8 months; 62,7% male gender), corresponding to 15% of all first appointments. Other comorbidities were present in 20% of the patients and 17% had ORL surgery prior to PID referral. In most patients, the immunologic screening consisted on the evaluation of humoral function, but in selected cases other studies were performed (namely complement and lymphocyte immunophenotyping). A PID was identified in 12 children (16,0%) and the majority of these patients had other distinctive feature (personal or familiar antecedent of infection or auto-immunity, 66,7%, p<0,05). Nine children (12,0%) underwent prophylactic cotrimoxazole. The average length of follow-up was 11,2 months. Conclusion: Despite being a very frequent cause of immunologic screening, in this study recurrent AOM was not found to be a good predictor of underlying PID, unless the patients presents other significant personal or family history.

Smart metering consumer behavior study in the Republic of Ireland: Further analyses on the consumers’ electricity consumptions and usage perceptions

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

Are annual budgets being abandoned by companies operating in Portugal?: Evidence from the 500 “Maiores e Melhores”

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

A happiness index of human development

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

Chagas' disease: an algorithm for donor screening and positive donor counseling

Classical serological screening assays for Chagas' disease are time consuming and subjective. The objective of the present work is to evaluate the enzyme immuno-assay (ELISA) methodology and to propose an algorithm for blood banks to be applied to Chagas' disease. Seven thousand, nine hundred and ninety nine blood donor samples were screened by both reverse passive hemagglutination (RPHA) and indirect immunofluorescence assay (IFA). Samples reactive on RPHA and/or IFA were submitted to supplementary RPHA, IFA and complement fixation (CFA) tests. This strategy allowed us to create a panel of 60 samples to evaluate the ELISA methodology from 3 different manufacturers. The sensitivity of the screening by IFA and the 3 different ELISA's was 100%. The specificity was better on ELISA methodology. For Chagas disease, ELISA seems to be the best test for blood donor screening, because it showed high sensitivity and specificity, it is not subjective and can be automated. Therefore, it was possible to propose an algorithm to screen samples and confirm donor results at the blood bank.

Public funding of higher education: who gains, who loses?

This paper analyses the effects of public funding of higher education on the welfare of the different agents. It takes into account the hierarchical nature of the educational system and also the fact that parents always have the possibility to complement basic public education with private expenditures in individual tutoring. It is obtained that although public funding implies a larger access to higher education it is always the case that some of the agents that gain access lose in welfare terms. Moreover, it is shown that the marginal agent to access university would always prefer a pure private funding system. Thus, when studying the effects of public funding of higher education, we can not identify gaining access to University with an increase in welfare. Finally, I consider a funding system where only those that send their o¤spring to university support the funding of higher education.

Sensitivity of polymerase chain reaction for detection of known aliquots of Trypanosoma cruzi in the blood of mice: an in vitro study

To evaluate the sensitivity of polymerase chain reaction (PCR) to reveal known number of trypomastigote in the blood of mice, three separate experiments were done. First: To eight samples of 500mul of normal mice blood, one aliquot of 1, 2, 3, 4, 5, 10, and 50 trypomastigotes respectively, were added. Second and third: 10 aliquots with 1 and 10 with 2 trypomastigotes were added to samples of 500mul of normal mice blood. Positive control: 500mul of blood containing 100,000 trypomastigotes. For kDNA minicircles amplification by PCR the primers:S35 and S36 were used. PCR revealed products of 330 b.p in the positive controls. When only one sample with the aliquots of 1 or 2 trypomastigotes was examined, results were negative; results were positive with aliquots of 3 to 50 trypomastigotes. In the 2nd and 3rd experiments, 9/10 aliquots with one parasite and 9/10 with 2 trypomastigotes were positive revealing a high sensitivity of this reaction. In conclusion, the presence of one single parasite in 500mul of blood, is enough for a positive PCR. This method could be used as a complement to the various parasitological cure tests in treated mice, when low volumes of blood are individually examined.

Prevalence of Epstein-Barr virus antibodies in healthy children and adolescents in Vitória, State of Espírito Santo, Brazil

The prevalence and age distribution of Epstein-Barr virus infection varies in different populations and there is little information about the epidemiology of this infection in Brazil. We studied the prevalence of EBV antibodies in a sample of 283 children and adolescents between 1 and 21 years old. The sample was taken from two neighborhoods in Vitória (capital city of Espirito Santo, Brazil). The São Pedro (SP) neighborhood represented an area with lower socioeconomic status and the Praias (P) neighborhood represented an area with higher SES. Anti-VCA (Virus Capsid Antigen) antibodies were detected by ELISA and anti-EBNA (Epstein-Barr Nuclear Antigen) antibodies were detected by an anti-complement immunofluorescence method, both using commercial kits. The results showed an overall prevalence rates of anti-VCA and anti-EBNA of 71% and 54% respectively. The prevalence for both anti-EBV antibodies was higher and probably the infection occurred earlier in the SP neighborhood. Among the various socioeconomic factors studied only low family income and maternal education level were significantly correlated with a higher frequency of positive serology for anti-VCA. These results demonstrate that there is a high prevalence of EBV antibodies in children and adolescents living in Vitória, that occurs more frequently at a younger age in children from families with low socioeconomic status. In addition, the results demonstrate an intermediate age distribution pattern between those reported in developed and underdeveloped countries.

Contribuição para o estudo da ocorrência da interrupção voluntária da gravidez em Portugal continental (1993 a 1997) : estimativas utilizando dados da rede de médicos sentinela e dos diagnósticos das altas hospitalares (grupos de diagnósticos homogéneos)

RESUMO - Apesar de existir em Portugal alguma informação sobre a epidemiologia da interrupção voluntária da gravidez (IVG), parece importante aumentar o conhecimento sobre este tema, complementando os estudos de base populacional disponíveis. O objectivo deste trabalho foi estimar a incidência de IVG na população feminina de Portugal continental com idade entre os 15 e os 44 anos entre os anos de 1993 a 1997. Utilizaram-se para tal dados gerados por dois sistemas de informação: o sistema de vigilância epidemiológica «Médicos Sentinela» e o sistema de informação de rotina baseado nos diagnósticos de alta hospitalar (grupos de diagnósticos homogéneos). Os resultados sugerem que no período em estudo terão ocorrido, em média, 3861,4 IVG/100 000 mulheres/ano, valor que terá sido mais elevado no grupo etário dos 25 aos 34 anos (5472,1 casos/100 000 mulheres/ano), enquanto o número de IVG por 1000 nados-vivos parece ter sido mais elevado entre os 35 e os 44 anos (2810,5 IVG/1000 nados- -vivos). Durante o período em estudo, a taxa de incidência de IVG terá diminuído de 6752,1 casos/100 000 mulheres em 1993 para 4339,2 casos/100 000 mulheres em 1997. A comparação dos indicadores calculados neste trabalho com os disponíveis para outros países sugere que, em Portugal, a IVG tem uma frequência superior à verificada no resto da Europa ocidental e do Sul. Torna-se necessário aprofundar este estudo para obter estimativas indirectas mais fiáveis da incidência de IVG, pelo menos até que esteja disponível um sistema de vigilância específico sobre este problema, em Portugal.

Development of a satellite based PM10 concentration product for urban areas

Dissertação para obtenção do Grau de Doutor em Engenharia do Ambiente

Thermal performance of cool facades: evaluation by Infrared Thermography

High reflective paints (cool paints) are used on flat roofs to reduce heat gains from the incidence of solar radiation and thus improve the thermal comfort and energy efficiency of buildings, especially in summer periods. Given the application potential of these paints on vertical surfaces, a research study has been developed to evaluate the thermal performance of reflective paints on walls under real exposure conditions. Accordingly, different reflective paints have been applied as the final coating of an ETICS type solution, on the facades of a full scale experimental cell built at LNEC campus. For being applied in an ETICS system a paint has to fulfill several requirements, whether aesthetic or functional (such as the adhesion between the coating layers or the durability of the insulation), essential for its efficient performance. Since this construction coating system is subject to a prolonged sun exposure, various problems may arise, such as paint degradation or deterioration of the thermal insulation properties, particularly when dark colors are applied. To evaluate the thermal performance of the chosen paints, the method of non-destructive analysis by Infrared Thermography was used. Thermography allows knowing the temperature distribution of facades by measuring the radiation emitted by their surfaces. To complement the thermographic diagnosis, thermocouples were placed between the insulation and the paint system of the experimental cell. Additional laboratory tests allowed the characterization of the optical properties (reflectance and emittance) of the different reflective paints used in this study. The comparative analysis of the thermal performance of reflective and conventional paints revealed that the reflective paint allows a reduction of the facade surface temperature, reducing the risk of loss of insulating properties of the ETICS system and thus ensuring its longevity and functionality. The color of the paint used affects, naturally, the reflective ability of the surface and may have an important role in energy balance of the building. This paper also showed the potential of infrared thermography in the evaluation of the thermal performance of reflective paints.

Melanosome transfer between melanocytes and keratinocytes

RESUMO: A pele é o maior órgão do corpo humano e a sua pigmentação é essencial para a sua coloração e proteção contra os efeitos nocivos da radiação ultravioleta (UV). A pigmentação da pele resulta essencialmente de três processos: a síntese e o armazenamento de melanina pelos melanócitos, em organelos especializados denominados melanossomas; o transporte dos melanossomas dentro dos melanócitos; e finalmente, a transferência dos melanossomas para os queratinócitos adjacentes. Nos queratinócitos, a melanina migra para a região perinuclear apical da célula para formar um escudo protetor,responsável pela proteção do DNA dos danos causados pela radiação UV. Os melanócitos estão localizados na camada basal da epiderme e contactam com 30-40 queratinócitos. Em conjunto, estas células formam a “unidade melano-epidérmica”. Apesar dos processos de síntese e transporte de melanina nos melanócitos estarem bastante bem caracterizados, os mecanismos moleculares subjacentes à transferência inter-celular de melanina são menos conhecidos e ainda controversos. Dados preliminares obtidos pelo nosso grupo, que se basearam na observação de amostras de pele humana por microscopia electrónica, indicam que a forma predominante de transferência de melanina na epiderme consiste na exocitose dos melanossomas pelos melanócitos e subsequente endocitose da melanina por queratinócitos. Para além disso sabe-se que as proteínas Rab, que controlam o tráfego membranar, estão envolvidas em várias etapas de pigmentação da pele, nomeadamente na biogénese e no transporte de melanina. Assim, dado o seu papel fundamental nestes processos, questionámo-nos sobre o seu envolvimento na transferência de melanina. Com este trabalho, propomo-nos a expandir o conhecimento atual sobre a transferência de melanina na pele, através do estudo detalhado dos seus mecanismos moleculares, identificando as proteínas Rab que regulam o processo. Pretendemos também confirmar o modelo de exo/endocitose como sendo o mecanismo principal de transferência de melanina. Primeiro, explorámos a regulação da secreção de melanina pelos melanócitos e analisámos o papel de proteínas Rab neste processo. Os resultados foram obtidos recorrendo a um método in vitro, desenvolvido previamente no laboratório, que avalia a quantidade de melanina segregada para o meio de cultura por espectrofotometria, e ainda por microscopia, contando o número de melanossomas transferidos para os queratinócitos. Através de co-culturas de melanócitos e queratinócitos, verificou-se que os queratinócitos estimulam a libertação de melanina dos melanócitos para o meio extra-celular, bem como a sua transferência para os queratinócitos. Além disso, a proteína Rab11b foi identificada como um regulador da exocitose de melanina e da sua transferência para os queratinócitos. De facto, a diminuição da expressão de Rab11b em melanócitos provocou a redução da secreção de melanina estimulada por queratinócitos, bem como da transferência desta. Em segundo lugar, para complementar o nosso estudo, centrámos a nossa investigação na internalização de melanina por queratinócitos. Especificamente, usando uma biblioteca de siRNA, explorámos o envolvimento de proteínas Rab na captação de melanina por queratinócitos. Como primeira abordagem, usámos esferas fluorescentes como substituto de melanina, avaliando os resultados por citometria de fluxo. No entanto, este método revelou-se ineficaz uma vez que a internalização destas esferas é independente do recetor PAR-2 (recetor 2 ativado por protease), que foi previamente descrito como essencial na captação de melanina por queratinócitos Posteriormente, foi desenvolvido um novo protocolo de endocitose baseado em microscopia, usando melanossomas sem a membrana envolvente (melanocores) purificados do meio de cultura de melanócitos, incluindo um programa informático especialmente desenhado para realizar uma análise semi-automatizada. Após internalização, os melanocores acumulam-se na região perinuclear dos queratinócitos, em estruturas que se assemelham ao escudo supranuclear observado na pele humana. Seguidamente, o envolvimento do recetor PAR-2 na captação de melanocores por queratinócitos foi confirmado, utilizando o novo protocolo de endocitose desenvolvido. Para além disso, a necessidade de quatro proteínas Rab foi identificada na internalização de melanocores por queratinócitos. A redução da expressão de Rab1a ou Rab5b em queratinócitos diminuiu significativamente o nível de internalização de melanocores, enquanto o silenciamento da expressão de Rab2a ou Rab14 aumentou a quantidade de melanocores internalizados por estas células. Em conclusão, os resultados apresentados corroboram as observações anteriores, obtidas em amostras de pele humana, e sugerem que o mecanismo de transferência predominante é a exocitose de melanina pelos melanócitos, induzida por queratinócitos, seguida por endocitose pelos queratinócitos. A pigmentação da pele tem implicações tanto ao nível da cosmética, como ao nível médico, relacionadas com foto-envelhecimento e com doenças pigmentares. Assim sendo, ao esclarecer quais os mecanismos moleculares que regulam a transferência de melanina na pele, este trabalho pode conduzir ao desenvolvimento de novas estratégias para modular a pigmentação da pele.----------------ABSTRACT: Skin pigmentation is achieved through the highly regulated production of the pigment melanin in specialized organelles, termed melanosomes within melanocytes. These are transported from their site of synthesis to the melanocyte periphery before being transferred to keratinocytes where melanin forms a supra-nuclear cap to protect the DNA from UVinduced damage. Together, melanocytes and keratinocytes form a functional complex, termed “epidermal-melanin unit”, that confers color and photoprotective properties to the skin. Skin pigmentation requires three processes: the biogenesis of melanin; its intracelular transport within the melanocyte to the cell periphery; and the melanin transfer to keratinocytes. The first two processes have been extensively characterized. However, despite significant advances that have been made over the past few years, the mechanisms underlying inter-cellular transfer of pigment from melanocytes to keratinocytes remain controversial.Preliminary studies from our group using electron microscopy and human skin samples found evidence for a mechanism of coupled exocytosis-endocytosis. Rab GTPases are master regulators of intracellular trafficking and have already been implicated in several steps of skin pigmentation. Thus, we proposed to explore and characterize the molecular mechanisms of melanin transfer and the role of Rab GTPases in this process. Moreover, we investigated whether the exo/endocytosis model is the main mechanism of melanin transfer. We first focused on melanin exocytosis by melanocytes. Then, we started to investigate the key regulatory Rab proteins involved in this step by establishing an in vitro tissue culture model of melanin secretion. Using co-cultures of melanocytes and keratinocytes, we found that keratinocytes stimulate melanin release and transfer. Moreover, depletion of Rab11b decreases keratinocyte-induced melanin exocytosis by melanocytes. In order to determine whether melanin exocytosis is a predominant mechanism of melanin transfer, the amount of melanin transferred to keratinocytes was then assayed in conditions where melanin exocytosis was inhibited. Indeed, Rab11b depletion resulted in a significant decrease in melanin uptake by keratinocytes. Taken together, these observations suggest that Rab11b mediates melanosome exocytosis from melanocytes and transfer to keratinocytes. To complement and extend our study, we of melanin by keratinocytes. Thus, we aimed to explore the effect of depleting Rab GTPases on melanin uptake and trafficking within keratinocytes. As a first approach, we used fluorescent microspheres as a melanin surrogate. However, the uptake of microspheres was observed to be independent of PAR-2, a receptor that is required for melanin uptakecentred our attention in the internalization of melanin by keratinocytes. Thus, we aimed to explore the effect of depleting Rab GTPases on melanin uptake and trafficking within keratinocytes. As a first approach, we used fluorescent microspheres as a melanin surrogate. However, the uptake of microspheres was observed to be independent of PAR-2, a receptor that is required for melanin uptake.Therefore, we concluded that microspheres were uptaken by keratinocytes through a different pathway than melanin. Subsequently, we developed a microscopy-based endocytosis assay using purified melanocores (melanosomes lacking the limiting membrane) from melanocytes, including a program to perform a semi-automated analysis. Melanocores are taken up by keratinocytes and accumulate in structures in the perinuclear area that resemble the physiological supranuclear cap observed in human skin. We then confirmed the involvement of PAR-2 receptor in the uptake of melanocores by keratinocytes, using the newly developed assay. Furthermore, we identified the role of four Rab GTPases on the uptake of melanocores by keratinocytes. Depletion of Rab1a and Rab5b from keratinocytes significantly reduced the uptake of melanocores, whereas Rab2a, and Rab14 silencing increased the amount the melanocores internalized by XB2 keratinocytes. In conclusion, we present evidence supporting keratinocyte-inducedmelanosome exocytosis from melanocytes, followed by endocytosis of the melanin core by keratinocytes as the predominant mechanism of melanin transfer in skin. Although advances have been made, there is a need for more effective and safer therapies directed at pigmentation disorders and also treatments for cosmetic applications. Hence, the understanding of the above mechanisms of skin pigmentation will lead to a greater appreciation of the molecular machinery underlying human skin pigmentation and could interest the pharmaceutical and cosmetic industries.

Buy, sell and chatter: A case analysis of a Lisbon flea market

This thesis aims explore the sociocultural as well as economic significance of the modern-day flea market, as a form of alternative marketplace system. More specifically, the main goal of the research is to determine the motivation for participation in flea markets of different participants, from vendors to consumers, using an interactionist perspective. By studying these groups in details, I seek to explore the embeddedness of social aspects in economic activity and vice versa. The basic assumption is to put aside the previous notions of the flea market as a second-order system with implied inferiority, and to explore the potential of the flea market to both challenge and complement more formal marketplace systems, by comparing and contrasting the flea market with market venues that belong to the formal sector. Feira da Ladra in Lisbon, Portugal, the oldest a hugely successful flea market in Europe, was chosen to be the research site, where its economic participants were studied in details in various exchanges, using naturalistic observations, semi-structured interviews and a sociocultural perspective.