Exopolysaccharide production by Enterobacter A47: optimization of cultivation conditions and study of polymer functional properties

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Control of parasitic infections among school children in the peri-urban area of Botucatu, São Paulo, Brazil

Tide prevalence of intestinal parasitosis ivas investigated in a primaiy school located in Rubiâo Júnior, a peri-urban district of Botucatu, São Paulo slate, Brazil, in order to assess the effect of treatment and practical measures of prophylaxis in the control of parasitic infections among 7-to- 18-year-old school children of a low socio-economic status. The first series of parasitological examinations included 219 school children, ef which 123 (56.1 %) were found to be infected with one or more parasite species. Eighty- four children canying pathogenic parasites were submitted to various anti-parasitic treatment schedules. We re-evaluated 15 (89 %) students after 4 to 6 months post- chemotherapy. The results indicate that the combination of treatment with prophylactic measures has been successful in the control of parasitic infections, since reinfection rates were generally low (< 5-3 %), except for Giardia lamblia infections (18.6 %), and a marked reduction oti the prevalence rates was obsewed with a significant percentage of cure (> 73-1 %) in children infected with most parasite species. The reasons for the apparent failure in the control of infections caused by Hymenolepis nana and Strongyloides stercoralis are discussed.

Avaliação clínica na disfunção fronto-estriatal : movimento e cognição

RESUMO: Os circuitos fronto-estriatais constituem um sistema em ansa fechada que une diversas regiões do lobo frontal aos gânglios da base, participando, com outras áreas cerebrais, no controlo do movimento, cognição e comportamento. As Distonias Primárias, a Doença de Parkinson e a Hidrocefalia de Pressão Normal, são doenças do movimento caracterizadas por disfunção do circuito fronto-estriatal motor. A conectividade funcional entre as diversas ansas do sistema fronto-estriatal, permite prever que as doenças do movimento possam também acompanhar-se de sintomas da esfera cognitiva e comportamental, cuja avaliação seria importante no manejo diagnóstico e terapêutico dos doentes. Objectivos Os nossos objectivos foram avaliar, por estudos clínicos, a relação entre sintomas motores, cognitivos e comportamentais em três doenças do movimento com fisiopatologias diversas - distonias Primárias, Doença de Parkinson e Hidrocefalia de Pressão Normal - analisando os dados sob a perspectiva teórica fornecida pelo conhecimentos dos vários circuitos frontoestriatais. Os nossos objectivos específicos para cada doença foram: a) Distonias Primárias: avaliação de disfunção executiva em doentes com Distonia Primária e relação com a gravidade dos sintomas motores b) Doença de Parkinson: 1. avaliação breve das funções mentais nas fases iniciais da doença, incluindo análise longitudinal para determinação de factores preditivos para declínio cognitivo; 2. relação entre a função motora e cognitiva e a Perturbação do Comportamento do sono REM, incluindo análise longitudinal; 3.avaliação de sintomas psiquiátricos, de um ponto de vista global e especificamente com incidência sobre as Perturbações do Controlo do Impulso (PCI). c) Hidrocefalia de Pressão Normal: 1. caracterização das alterações da marcha, incluindo comparação com a Doença de Parkinson; 2. caracterização das alterações cognitivas e da relação entre estas e a disfunção da marcha; 3. estudo evolutivo das alterações da marcha e cognitiva em doentes submetido a cirurgia e doentes não submetidos a cirurgia. Métodos: A Distonia Primária, a Doença de Parkinson e a Hidrocefalia de Pressão Normal foram diagnosticadas segundo critérios clínicos validados. Sempre que justificado, foram recrutados grupos de controlo, com indivíduos sem doença, emparelhados para idade, sexo e grau de escolaridade. Os doentes foram avaliados com instrumentos de aplicação clinica directa, incluindo escalas de função motora, testes neuropsicológicos globais e dirigidos às funções executivas e escalas de avaliação psiquiátrica. Testes aplicados nas Distonias Primárias: Unified Dystonia Rating Scale, Wisconsin Card Sorting Test, teste de Stroop, teste de cubos da WAIS, Teste de Retenção Visual de Benton; na Doença de Parkinson: Unified Parkinson's Disease Rating Scale, Frontal Assessment Battery (FAB), Mini-Mental State Examination (MMSE), REM-sleep behaviour disorder Questionnaire; Symptom Chek-list 90-R, Brief Psychiatric Rating Scale, FAS (fluência verbal lexical) Nomeação de Animais (Fluência verbal semântica), prova de repetição de dígitos (WAIS), Rey auditory verbal learning test, teste de Stroop, matrizes progressivas de Raven, Questionnaire for Impulsive-Compulsive Disorders; na HPN: prova cronometrada de marcha,MMSE, prova de memória imediata da WAIS, prova de repetição de dígitos (WAIS), FAB, desenho complexo de Rey, teste de Stroop, cancelamento de letras, teste Grooved Pegboard. Os doentes com HPN foram também submetidos a estudo imagiológico. A avaliação estatística foi adaptada às características de cada um dos estudos.Resultados Distonias Primárias: encontrámos défices de função executiva, envolvendo dificuldade na mudança entre sets cognitivos, bem como correlação significativa entre as pontuações nos testes cronometrados e a gravidade dos sintomas motores. Doença de Parkinson: os doentes com DP obtiveram pontuações significativamente inferiores na FAB e em sub-testes do MMSE (memória e função visuo-espacial). A pontuação no MMSE encontrava-se significativamente correlacionada com itens da função motora não relacionados com o tremor. A disfunção da marcha, a disartria, o fenótipo não tremorígeno, a presença de alucinações e pontuação abaixo do ponto de corte na MMSE, foram factores preditivos de demência na avaliação longitudinal. A rigidez e a disartria foram factores preditivos de declínio nas funções frontais. A disfunção frontal foi factor preditivo de declínio na pontuação do MMSE. Encontrámos uma prevalência elevada de RBD nas fases iniciais da DP, que o estudo longitudinal mostrou ser factor preditivo de declínio motor, nomeadamente por agravamento da bradicinésia. Encontrámos também uma prevalência elevada de sintomas psiquiátricos, nomeadamente psicose, depressão, ansiedade, somatização e sintomas obsessivo-compulsivos. As PCI não se encontravam relacionadas com o fenótipo motor, com as complicações motoras do tratamento dopaminérgico ou com a disfunção cognitiva. HPN: os doentes com HPN e os DP apresentaram um padrão disfunção da marcha semelhante, caraterizado por passos curtos, lentidão e dificuldades de equilíbrio, sendo os sintomas mais graves na HPN. Os doentes de Parkinson com maior duração de doença, maior dose de dopaminérgicos e fenótipo motor acinético-rígido apresentaram um padrão de disfunção da marcha de gravidade semelhante ao encontrado na HPN. As alterações vasculares da substância branca, em particular as encontradas na região frontal, encontravam-se negativamente correlacionadas com a melhoria da marcha após PL. O estudo das funções cognitivas mostrou um padrão de atingimento global, com valores mais baixos na cópia do desenho complexo de Rey. Os resultados nas provas de função cognitiva não se encontravam significativamente correlacionados com os resultados na prova da marcha. A progressão na disfunção da marcha encontrava-se relacionada com o tratamento não cirúrgico, idade superior na primeira avaliação, presença de lesões da substância branca, e presença de factores de risco vascular, ao passo que não foram encontrados factores que predissessem de modo significativo o agravamento da função cognitiva. Conclusões: Os resultados dos diversos estudos, evidenciam a presença de alterações cognitivas e comportamentais nas três doenças de movimento. O padrão destas alterações e o modo como estas se relacionaram com os sintomas motores variou de doença para doença. Nas Distonias primárias, a perseveração cognitiva poderá ser o sintoma correspondente à perseveração motora própria da doença, sugerindo disfunção no circuito dorso-lateral frontoestriatal. A correlação entre a gravidade motora da doença e o resultado nos testes cognitivos cronometrados, poderá ser o efeito da relação entre bradicinésia e bradifrenia. Na Doença de Parkinson, o espectro de alterações é mais acentuado, espelhando a disseminação do processo degenerativo no SNC. Para além dos sintomas de disfunção executiva, sugerindo disfunção das tês ansas não motoras, existem sinais de disfunção cognitiva global, estas com uma influência mais significativa no desenvolvimento da demência. A relação entre os diferentes sintomas motores e cognitivos é também complexa, embora se evidencie uma dissociação significativa entre o tremor, sem relação com os sintomas não motores, e os sintomas motores não tremorígenos, relacionados com o declínio cognitivo. Enquanto que a presença de RBD parece ser um factor preditivo de agravamento motor, os sintomas psiquiátricos, também muito frequentes, apresentam uma relação menos clara com a função motora. Destes, os sintomas obsessivo-compulsivos são aqueles que com mais frequência se atribuem a disfunção do sistema fronto-estriatal, nomeadamente da ansa orbito-frontal. As PCI também não mostraram ter relação com os sintomas motores ou cognitivos. Na HPN, é patente o carácter fronto-estriatal das alterações da marcha, demonstrado tanto na sua caracterização quanto no efeito deletério das lesões vasculares da substância branca do lobo frontal na recuperação da marcha após PL. As alterações cognitivas parecem ter um padrão mais difuso, o que talvez explique a falta de correlação com os sintomas motores - esta dissociação pode ser causada quer por diferença nos mecanismos fisiopatológicos quer por presença de comorbilidades cognitivas. --------- ABSTRACT: Fronto-striatal circuits constitute a closed loop system which connects different parts of the frontal lobes to the basal ganglia. They are engaged in motor, cognitive and behavioural control. Primary Dystonia, Parkinson's Disease and Normal-Pressure Hydrocephalus are movement disorders caused by disturbance of the motor fronto-striatal circuit. The existence of cognitive and behavioural dysfunction in these movement disorders is predictable, given the functional connectivity between the several distinct loops of the circuit. Evaluation of cognitive and behavioural dysfunction in these three disorders is thus both of clinical and theoretical relevance. Objectives Our objectives were to evaluate, by clinical means, the relation between motor, cognitive and behavioural symptoms in three movement disorders with different pathophysiological backgrounds - Primary Dystonia, Parkinson's Disease and Normal-Pressure Hydrocephalus - and to analyse the study results under the theoretical framework formed by present knowledge of the fronto-estriatal system. Specific objectives: a) Primary Dystonia: executive dysfunction assessment and correlation analysis with motor dysfunction severity; b) Parkinson's Disease: 1. brief cognitive assessment in the early stages of disease, including a longitudinal analysis for determination of predictive factors for cognitive decline; 2. to investigate the relation between RBD and cognitive and motor dysfunction, including a longitudinal analysis; 3. psychiatric symptom assessment, with particular incidence on Impulse Control Disorders; c) Normal-Pressure Hydrocephalus: 1. gait dysfunction characterization and comparison with Parkinson's Disease patients; 2. determination of cognitive dysfunction profile and its relation with gait dysfunction; 3. follow-up study of cognitive and motor outcome in patients submitted and not submitted to shunt surgery. Methods: Primary Dystonia, Parkinson's Disease and Normal Pressure Hydrocephalus were diagnosed according to clinically validate criteria. Where warranted, we recruited control groups formed by healthy individuals, matched for age, sex and educational level. Patients were evaluated with instruments of direct clinical application, including motor function scales, neuropsychological tests aimed at global and executive functions and psychiatric rating scales. Tests used in Primary Dystonia: Unified Dystonia Rating Scale, Wisconsin Card Sorting Test, Stroop Test, Cube Assembly test (WAIS), Benton’s Visual Retention Test; in Parkinson's Disease: Unified Parkinson's Disease Rating Scale, Frontal Assessment Battery (FAB) , Mini-mental State Examination (MMSE), REM-sleep behavior disorder Questionnaire, Symptom Check-list 90- R, Brief Psychiatric Rating Scale, FAS (phonetic verbal fluency), semantic verbal fluency test, digit span test (WAIS), auditory verbal learning test,Stroop test, Raven's progressive Matrices, Questionnaire for Impulsive-Compulsive Disorders; in NPH: timed walking test, MMSE, immediate memory task (WAIS), digit span test (WAIS), FAB, Rey’s Complex Figure test, Stroop test, letter cancellation test, Perdue Pegboard test. NPH patients were also subjected to an imaging study. Statistics were adapted to the characteristics of each study.Results: Primary Dystonia: we found set-shifting deficits as well as significant correlation between timed neuropsychological tests and dystonia severity. Parkinson's Disease: PD patients had significantly lower scores on the FAB and on the memory and visuo-spatial tests of the MMSE; MMSE scores were significantly correlated to non-tremor motor scores; gait dysfunction and speech scores, non-tremor motor phenotype, hallucinations and scores bellow cut-off on the MMSE were predictive of dementia at follow-up; speech and rigidity scores were predictive of frontal type decline; frontal dysfunction was predictivy of decline in MMSE scores; RBD bradykinesia worsening; psychiatric symptoms were prevalent, particularly Psychosis, Depression, Anxiety, Somatisation and Obsessive-Compulsive Symptoms; Impulse Control Disorders were unrelated to motor phenotype,motor side effects of dopamine treatment and executive function; NPH: gait dysfunction was worse in NPH when compared to PD patients, although the pattern was similarly characterized by slowness, short steps and disequilibrium; PD patients whose gait disturbance was as severe as that of NPH patients were characterized by longer disease duration, predominance of non-tremor motor scores, more advanced disease stage and higher dopamine dose; frontal white matter lesions correlated negatively with improvement after LP; cognitive function assessment revealed wide spread deficits, with lower results on the drawing of the complex figure of Rey, which were not significantly correlated to gait dysfunction; older age, white matter lesions and the presence of vascular risk factors were predictive factors for motor but not cognitive function worsening. Conclusion: Results from our studies highlight the presence of cognitive and behavioural dysfunction in all three movement disorders. Symptom pattern and the relation with ovement derangement varied according to the disease. In Primary Dystonia, set-shifting difficulties could be the cognitive counterpart of motor perseveration characteristic of this disorder, suggesting dysfunction of the dorso-lateral circuit. The relation between timed tests and dystonia severity could suggest a relation between bradyphrenia and bradykinesia in Primary Dystonia. In Parkinson's Disease patients, the spectrum of non-motor symptoms is wider, probably reflecting the spread of neurodegeneration beyond the fronto-striatal circuits. While frontal type deficits predominate, suggestive of dorso-lateral and orbito-frontal dysfunction, non-frontal deficits were also apparent in the initial stages of disease, and were predictive of dementia at follow-up. The relationship between cognitive and motor symptoms is complex, although the results strongly suggest a dissociation between tremor symptoms, which bore no relation with non-motor symptoms, and non-tremor symptoms,whichwas frequent, and a predictive factor for which were related with cognitive decline. While RBD was found to be a predictive factor for bradykinesia worsening, psychiatric symptoms, which were also frequent, showed no apparent relation with motor dysfunction. Relevant to our theoretical consideration was the high prevalence of OCS, which have been attributed to orbito-frontal dysfunction. As to the particular case of ICD, we found no relation either with motor or cognitive dysfunction. The fronto-striatal nature of gait dysfunction in NPH is suggest by the clinical characterization study and by the effects of frontal white matter lesions on gait recovery after LP, whereas cognitive dysfunction presented a more diffuse pattern, which could explain the lack or relation with gait assessment results and also the different outcome on the longitudinal study - this dissociation could be caused by a real difference in pathophysiological mechanisms or, in alternative, be due to the existence of cognitive comorbidities.

Trypanosoma cruzi in marsupial didelphids (Philander frenata and Didelhis marsupialis): differences in the humoral immune response in natural and experimental infections

Philander frenata and Didelphis marsupialis harbor parasitism by Trypanosoma cruzi without developing any apparent disease and on the contrary to D. marsupialis, P. frenata maintains parasitism by T. cruzi II subpopulations. Here we compared the humoral immune response of the two didelphids naturally and experimentally infected with T. cruzi II group, employing SDS-PAGE/Western blot techniques and by an Indirect immunofluorescence assay. We also studied the histopathological pattern of naturally and experimentally infected P. frenata with T. cruzi. P. frenata sera recognized more antigens than D. marsupialis, and the recognition pattern did not show any change over the course of the follow up of both didelphid species. Polypeptides of 66 and 90kDa were the most prominent antigens recognized by both species in the soluble and enriched membrane fractions. P. frenata recognized intensely also a 45kDa antigen. Our findings indicate that: 1) there were no quantitative or qualitative differences in the patent or subpatent phases in the recognition pattern of P. frenata; 2) the significant differences in the recognition pattern of parasitic antigens by P. frenata and D. marsupialis sera suggest that they probably "learned" to live in harmony with T. cruzi by different strategies; 3) although P. frenata do not display apparent disease, tissular lesions tended to be more severe than has been described in D. marsupialis; and 4) Both didelphids probably acquired infection by T. cruzi after their evolutionary divergence.

Clinical presentation of parvovirus B19 infection in HIV-infected patients with and without AIDS

Human parvovirus B19 replicates in erythrocyte precursors. Usually, there are no apparent hematological manifestations. However, in individuals with high erythrocyte turnover, as in patients with sickle-cell disease and in the fetus, the infection may lead to severe transient aplasia and hydrops fetalis, respectively. In AIDS patients, persistent infection may result in chronic anemia. By contrast, in HIV-positive patients without AIDS the infection evolves as a mild exanthematous disease. Two clinical descriptions exemplify these forms of presentation. In the first, an AIDS patient presented with bone marrow failure that responded to immunoglobulin. In the second, an HIV-positive patient without AIDS had a morbilliform rash, and needed no treatment. Knowing that an AIDS patient has chronic B19 anemia lessens concern about drug anemia; protects the patient from invasive diagnostic maneuvers; and prevents the patient from disseminating the infection. In AIDS patients with pure red cell aplasia, a search for parvovirus B19 DNA in the serum or in the bone marrow is warranted.

Dynamic adaptation of interaction models for stateful web services

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Human pseudomyiasis caused by Eristalis tenax (Linnaeus) (Diptera: Syrphidae) in Goiás

The objective of the present work was to register the first proven cases of human pseudomyiasis due to Eristalis tenax in Goiás State, Brazil, underscoring their clinical manifestations and direct relationship with hygiene. The taxonomic identification of the instars was done according to the descriptions and keys presented by James (1947), Hartley (1961) and Guimarães & Papavero (1999). Two cases were observed. In both cases there was no evidence of apparent mental disturbance. The clinical picture of these cases was self limited. The water supply, sewer system, socioeconomic level and habits of the suspect species of the flies are criteria that should be investigated.

Brotherly love and filial obedience: the commemorative programme of the Avis princes at Santa Maria da Vitória, Batalha

This dissertation focuses on a rare 15th century commemorative programme that has thus far received little scholarly attention: the collective monument erected in the Founder’s Chapel, at the Monastery of Santa Maria da Vitória, Batalha, to house the remains of four Avis princes, members of what would become known as ‘the Illustrious Generation’. A patron is proposed for the commission of this erudite monument - the princes’ eldest brother, king Duarte I - arguing its integration into a broader propaganda programme to glorify the memory of the Avis dynasty founder, king João I. The dissertation then proceeds to discuss various highly innovative features of the monument, such as its pseudo-architectural character, its use of sophisticated heraldry and personal badges, the apparent absence of religious iconography on the tombs and, importantly, the collective nature of the programme, key to its interpretation. Using a semiotic approach, a discussion is also offered on the way the various formal, iconographic and conceptual novelties of the princes’ monument impacted on the 15th century monumental landscape in Portugal. Finally, the monument and the chapel housing it are looked at through the prism of the various readings that successive generations of viewers have projected onto it, from the time of its creation to the turn of the 20th century, in order to offer a more comprehensive understanding of the object as it stands today.

Exposição profissional ao chumbo : análise da indução de efeitos genotóxicos

RESUMO - A exposição contínua a substâncias químicas tem consequências para a saúde humana, algumas das quais não estão ainda totalmente estabelecidas. A toxicologia ocupacional é uma área interdisciplinar que envolve conhecimentos de higiene e de medicina ocupacional, de epidemiologia e de toxicologia e que tem por principal objectivo prevenir a ocorrência de efeitos adversos decorrentes do ambiente ocupacional sendo um dos seus principais papéis fornecer o máximo de dados que possam contribuir para o conhecimento dos potenciais efeitos na saúde. O chumbo é um tóxico de características cumulativas que provoca na saúde efeitos principalmente sistémicos, ou seja, o efeito tóxico manifesta-se em locais afastados do contacto inicial que resultam essencialmente de exposições crónicas, resultantes de períodos de exposição mais ou menos longos ao metal (entre meses e anos). Pode interagir com diferentes órgãos e tecidos, ligando-se a moléculas e constituintes celulares. Uma vez que não possui qualquer função fisiológica, a presença do chumbo no organismo humano resulta numa série de efeitos prejudiciais que afectam diversos órgãos e sistemas. A toxicidade do chumbo manifesta-se em diversos órgãos e tecidos, nomeadamente no sistema hematopoiético, no sistema nervoso, no rim, no aparelho reprodutor, no sistema cardiovascular, no sistema endócrino e no sistema imunitário. Da interferência do chumbo com o funcionamento de alguns sistemas biológicos resultam um conjunto de alterações fundamentais ao nível dos processos de transporte através das membranas, da integridade estrutural e funcional das enzimas e de várias vias metabólicas, em especial da fosforilação oxidativa e da síntese do heme sendo os primeiros efeitos bioquímicos do chumbo detectados a partir de valores de plumbémia inferiores a 10 μg/dL. As medidas de higiene e segurança actualmente em vigor nos países desenvolvidos asseguram que os casos de intoxicação grave são cada vez menos frequentes. No entanto, o risco de exposição a nível ocupacional existe em todas as actividades que envolvem materiais que o contenham como as explorações mineiras, as fundições primária e secundária, a produção de baterias de chumbo ácido, a produção de vidro com pigmentos de chumbo, as soldaduras de reparação automóvel e a instrução de tiro. Desde 2006 o chumbo é considerado pela International Agency for Research on Cancer (IARC) uma substância carcinogénica do grupo 2A (provável carcinogénio para o ser humano). Considera-se, assim, que o chumbo tem, inequivocamente, capacidade de induzir cancro em animais experimentais mas que, embora haja fortes indícios de que os mecanismos que medeiam a carcinogénese desses compostos ocorrem no ser humano, os dados disponíveis ainda não podem assegurar essa relação. Com este estudo pretendeu-se contribuir para o conhecimento da toxicidade do chumbo através do estudo da exposição ao chumbo e da influência da susceptibilidade individual (em industrias sem co-exposição significativa a outros agentes conhecidos ou suspeitos de serem carcinogénicos). Pretendeu-se estudar o caso através de uma abordagem múltipla que permitisse relacionar diferentes tipos de marcadores biológicos uma vez que a monitorização biológica integra todas as possíveis vias de entrada no organismo (para além da via respiratória), eventuais exposições fora do contexto estritamente profissional assim como uma série de factores intrínsecos individuais (relacionados com modos de via, de natureza fisiológica e comportamentais). Sendo a co-exposição a outros compostos com propriedades genotóxicas e carcinogénicas uma questão difícil de tornear quando se quer avaliar o potencial genotóxico do chumbo em populações expostas, ocupacional ou ambientalmente este estudo tem a vantagem de ter sido efectuado em populações sem co-exposição conhecida a outras substâncias deste tipo, permitindo concluir sobre os efeitos resultantes apenas da exposição a chumbo na população humana, contribuindo para explicar algumas das aparentes inconsistências e contradições entre diferentes estudos sobre este tema. Os indicadores de exposição usados foram: indicadores de dose interna (doseamento de chumbo e de PPZ no sangue), indicadores de efeitos adversos no heme e genotóxicos (actividade da ALAD, teste do cometa e mutação em TCR) e indicadores de susceptibilidade (polimorfismos genéticos de ALAD e VDR) através de uma abordagem estatística de comparação directa de sub-grupos previamente definidos na população e da aplicação de um modelo de regressão múltipla. Este estudo revelou que os níveis de plumbémia na população portuguesa baixaram significativamente nos últimos 10 anos, tanto na população ocupacionalmente exposta como na população em geral e que a presença do genótipo B-B (do gene VDR) é preditiva das variações de plumbémia, quando comparada com o genótipo mais frequente na população, B-b; ao contrário, o genótipo b-b não aparenta ter influência em nenhum dos marcadores estudados. No que diz respeito a efeitos genotóxicos concluiu-se que estes não se manifestaram na população estudada, levando a concluir que nos níveis de exposição estudados, o chumbo não tem capacidade de induzir este tipo de efeitos per si levando ao reforço da hipótese, já levantada por outros autores, de que o mecanismo de genotoxicidade do chumbo seja essencialmente de promoção de processos de genotoxicidade desencadeados por outros agentes. A realização de estudos de efeitos genotóxicos e de stress oxidativo desenhados de forma a comparar grupos de trabalhadores expostos apenas a chumbo com grupos de trabalhadores com o mesmo nível de exposição a chumbo, mas com co-exposição a outros agentes reconhecidamente carcinogénicos poderá ajudar a aumentar o conhecimento deste efeito do chumbo na saúde humana.

How Does Cultural Context Stimulate Creativity: A study of African Musicians in Lisbon, Portugal

The 21st century bodes an interesting time for companies and individuals alike with an increased focus on using creativity as a way to stimulate innovation to create competitive advantage. Several studies have looked at how creativity is stimulated within a corporate environment or how creativity is stimulated by people in a specific place. This study aimed to look at how the contextual environment fosters creativity in individuals and groups. With the increase in popularity of African and world music In Europe over the last ten years it was decided that the context of Lisbon, Portugal be used with a specific focus on African musicians living there and working in the Lisbon music scene. It became apparent themes of Creative crossovers, Geographical Location, a dynamic environment, Entrepreneurial encouragement and the presence of open-minded and flexible individual were involved in Lisbon’s ability to foster and empower creative individuals.

Assessment by doppler ultrasound of entheseal lesions in spondyloarthritis : a longitudial study to determine structural damage and disease activity lesions

RESUMO: Enthesitis is the hallmark of spondyloarthritis (SpA), and is observed in all subtypes. Wide information on SpA abnormalities, including synovitis, tendinitis and enthesitis, can be efficiently perceived by Doppler ultrasound. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect enthesis alterations; and vascularized enthesitis detected by Doppler ultrasound appears to be a valuable diagnostic tool to confirm SpA diagnosis. However, data published until now concerning entheseal elementary alterations that characterize SpA enthesitis (enthesis inflammatory activity) or enthesopathy (permanent structural changes) reflect rather the authors’ empiric opinion than a methodological validation process. In this sense it seems crucial to identify elementary entheseal lesions associated with activity or damage, in order to improve monitoring and treatment response in SpA patients. The development of better assessment tools is today a challenge and a need in SpA. The first study of this thesis focused on the analysis of the reliability of inter-lector and inter-ultrasonography equipment of Madrid sonography enthesitis index (MASEI). Fundamental data for the remaining unrolling project validity. In the second and third studies we concerned about two entheseal elemental lesions: erosions and bursa. In literature erosions represent a permanent structural damage, being useful for monitoring joint injury, disease activity and therapeutic response in many rheumatic diseases; and to date, this concept has been mostly applied in rheumatoid arthritis (RA). Unquestionably, erosion is a tissue-related damage and a structural change. However, the hypothesis that we decided to test was if erosions represent a permanent structural change that can only grow and worsen over time, as occurs in RA, or a transitory alteration. A longitudinal study of early SpA patients was undertaken, and the Achilles enthesis was used as a model. Our results strongly suggested that previously detected erosions could disappear during the course of the disease, being consistent with the dynamic behavior of erosion over time. Based on these striking results it seems reasonable to suggest that the new-bone formation process in SpA could be associated with the resolution of cortical entheseal erosion over time. These results could also be in agreement with the apparent failure of anti-tumor necrosis factor (TNF) therapies to control bone proliferation in SpA; and with the relation of TNF-α, Dickkopf-related protein 1 (Dkk-1) and the regulatory molecule of the Wnt signaling pathway in the bone proliferation in SpA. In the same model, we then proceeded to study the enthesis bursa. Interestingly, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) enthesopathy definition does not include bursa as an elementary entheseal lesion. Nonetheless, bursa was included in 46% of the enthesis studies in a recently systematic literature review, being in agreement with the concept of “synovio-entheseal complex” that includes the link between enthesitis and osteitis in SpA. It has been clarified in recent data that there is not only a close functional integration of the enthesis with the neighboring bone, but also a connection between enthesitis and synovitis. Therefore, we tried to assess the prevalence and relevance of the bursa-synovial lesion in SpA. Our findings showed a significant increase of Achilles bursa presence and thickness in SpA patients compared to controls (healthy/mechanical controls and RA controls). These results raise awareness to the need to improve the enthesopathy ultrasonographic definition. In the final work of this thesis, we have explored new perspectives, not previously reported, about construct validity of enthesis ultrasound as a possible activity outcome in SpA. We performed a longitudinal Achilles enthesis ultrasound study in patients with early SpA. Achilles ultrasound examinations were performed at baseline, six- and twelve-month time periods and compared with clinical outcome measures collected at basal visit. Our results showed that basal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are higher in patients with Doppler signal in enthesis, and even that higher basal ESR, CRP and Ankylosing Spondylitis Disease Activity Score (ASDAS) predicted a higher Doppler signal (an ultrasound alteration accepted as representative of inflammation) six months later. Patients with very high disease activity assessed by ASDAS (>3.5) at baseline had significantly higher Achilles total ultrasound score verified at the same time; and ASDAS <1.3 predicted no Doppler signal at six and twelve months. This seems to represent a connection between classical biomarkers and clinical outcomes associated with SpA activity and Doppler signal, not only at the same time, but also for the following months. Remarkably, patients with inactive disease (ASDAS < 1.3) at baseline had no Doppler signal at six and twelve months. These findings reinforce the potential use of ultrasound related techniques for disease progression assessment and prognosis purposes. Intriguingly, Ankylosing Spondylitis Disease Activity Index (BASDAI) didn’t show significant differences between different cut-offs concerning ultrasound lesions or Doppler signal, while verified with ASDAS. These results seem to indicate that ASDAS reflects better than BASDAI what happens in the enthesis. The work herein discussed clearly shows the potential utility of ultrasound in enthesis assessment in SpA patients, and can be important for the development of ultrasound activity and structural damage scores for diagnosis and monitoring purposes. Therefore, local promotion of this technique constitutes a medical intervention that is worth being tested in SpA patients for diagnosis, monitoring and prognosis purposes.

Bone tuberculosis: a case report on child

The authors report a case of a 12-year-old child with a complaint of pain and deformity in the lower thoracic region that had lasted for two years. Clinical, epidemiological and laboratory characteristics associated with images of apparent damage in the T9-T10 and T11-T12 vertebrae taken by radiography of the thoracic spine and nuclear magnetic resonance in addition to the positivity of the molecular test based on the polymerase chain reaction, led to tuberculous spondylitis being diagnosed and specific therapy was started. Culture of vertebral biopsy was positive for Mycobacterium tuberculosis after thirty days.

Optimal design and operation of compact simulated moving bed processes for enantioseparations

Simulated moving bed (SMB) chromatography is attracting more and more attention since it is a powerful technique for complex separation tasks. Nowadays, more than 60% of preparative SMB units are installed in the pharmaceutical and in the food in- dustry [SDI, Preparative and Process Liquid Chromatography: The Future of Process Separations, International Strategic Directions, Los Angeles, USA, 2002. http://www. strategicdirections.com]. Chromatography is the method of choice in these ¯elds, be- cause often pharmaceuticals and ¯ne-chemicals have physico-chemical properties which di®er little from those of the by-products, and they may be thermally instable. In these cases, standard separation techniques as distillation and extraction are not applicable. The noteworthiness of preparative chromatography, particulary SMB process, as a sep- aration and puri¯cation process in the above mentioned industries has been increasing, due to its °exibility, energy e±ciency and higher product purity performance. Consequently, a new SMB paradigm is requested by the large number of potential small- scale applications of the SMB technology, which exploits the °exibility and versatility of the technology. In this new SMB paradigm, a number of possibilities for improving SMB performance through variation of parameters during a switching interval, are pushing the trend toward the use of units with smaller number of columns because less stationary phase is used and the setup is more economical. This is especially important for the phar- maceutical industry, where SMBs are seen as multipurpose units that can be applied to di®erent separations in all stages of the drug-development cycle. In order to reduce the experimental e®ort and accordingly the coast associated with the development of separation processes, simulation models are intensively used. One impor- tant aspect in this context refers to the determination of the adsorption isotherms in SMB chromatography, where separations are usually carried out under strongly nonlinear conditions in order to achieve higher productivities. The accurate determination of the competitive adsorption equilibrium of the enantiomeric species is thus of fundamental importance to allow computer-assisted optimization or process scale-up. Two major SMB operating problems are apparent at production scale: the assessment of product quality and the maintenance of long-term stable and controlled operation. Constraints regarding product purity, dictated by pharmaceutical and food regulatory organizations, have drastically increased the demand for product quality control. The strict imposed regulations are increasing the need for developing optically pure drugs.(...)

Osteoarticular tuberculosis in an HIV-positive patient: a case report

The authors report a case of a 38-year-old HIV-positive woman, with subcutaneous nodules on the thoracic region with 3 months of evolution. Clinical, laboratory, and epidemiological features were evaluated and associated with apparent damage to the T11-T12 vertebrae, identification by imaging tests, positivity in a polymerase chain reaction-based test, and reactivity to the Mantoux tuberculin skin test (PPD-RT 23). The patient was diagnosed with osteoarticular tuberculosis and received treatment for a year, and clinical cure was achieved.

Reflux esophagitis and gastroesophageal reflux disease: a cross-sectional study of gastroesophageal reflux disease patients by age group

The purpose of this study was to explore the relationship between the intensity of acid reflux and severity of esophageal tissue damage in a cross-sectional study of patients with gastroesophageal reflux disease (GERD). Seventy-eight patients with were selected in accordance with the strict 24-hour ambulatory esophageal pHmetry (24h-pHM) criteria and distributed into three age groups: Group A: 14 - 24 years of age. Group B: 25 - 54; and Group C: 55 - 64. The 24h-pHM was carried out in accordance with DeMeester standardization, and the Savary-Miller classification for the diagnosis of reflux esophagitis was used. The groups were similar in 24h-pHM parameters (p > 0.05), having above normal values. For the study group as a whole, there was no correlation between age group and intensity of acid reflux, and there was no correlation between intensity of acid reflux and severity of esophageal tissue damage. However, when the same patients were sub-grouped in accordance with the depth of their epithelial injury and then distributed into age groups, there was a significant difference in esophagitis without epithelial discontinuity. Younger patients had less epithelial damage than older patients. Additionally, although there was a significant progression from the least severe to the moderate stages of epithelial damage among the age groups, there was no apparent difference among the age groups in the distribution between the moderate stages and most severe stages. The findings support the conclusion that the protective response of individuals to acid reflux varies widely. Continued aggression by acid reflux appears to lead to the exhaustion of individual mechanisms of epithelial protection in some patients, but not others, regardless of age or duration of the disease. Therefore, the diagnosis and follow-up of GERD should include both measurements of the quantity of refluxed acid and an assessment of the damage to the esophageal epithelium.