Manifestações extra-glandulares do síndrome de Sjögren primário - doença linfoproliferativa e vasculite : clínica, diagnóstico, tratamento e prognóstico : Caso clínico e revisão bibliográfica

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Queratocone : impacto psico-social da doença na vida do doente

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Regulation of lipocalin prostaglandin-D synthase expression by interleukin-1β in human chondrocytes

L'arthrose est une maladie multifactorielle complexe. Parmi les facteurs impliqués dans sa pathogénie, les certains prostaglandines exercent un rôle inflammatoire et d’autres un rôle protecteur. La prostaglandine D2 (PGD2) est bien connue comme une PG anti-inflammatoire, qui est régulée par l’enzyme «Lipocalin prostaglandine D-synthase». Avec l’inflammation de l'arthrose, les chondrocytes essaient de protéger le cartilage en activant certaines voies de récupération dont l'induction du gène L-PGDS. Dans cette étude, nous étudions la voie de signalisation impliquée dans la régulation de l'expression du (L-PGDS) sur les chondrocytes traités avec différents médiateurs inflammatoires. Le but de projet: Nous souhaitons étudier la régulation de la L-PGDS dans le but de concevoir des approches thérapeutiques qui peuvent activer la voie intrinsèque anti-inflammatoire. Méthode et conclusions: In vivo, l'arthrose a été suivie en fonction de l’âge chez la souris ou chirurgicalement suivant une intervention au niveau des genoux de souris. Nous avons confirmé les niveaux d’expression de L-PGDS histologiquement et par immunohistochimie. In vitro, dans les chondrocytes humains qui ont été traités avec différents médiateurs de l'inflammation, nous avons observé une augmentation de l’expression de la L-PGDS dose et temps dépendante. Nous avons montré, in vivo et in vitro que l’inflammation induit une sécrétion chondrocytaire de la L-PGDS dans le milieu extracellulaire. Enfin, nous avons observé la production de différentes isoformes de la L-PGDS en réponse à l'inflammation.

Coreferentiality: A New Method for the Hypothesis-Based Analysis of Phenotypes Characterized by Multivariate Data

Many multifactorial biologic effects, particularly in the context of complex human diseases, are still poorly understood. At the same time, the systematic acquisition of multivariate data has become increasingly easy. The use of such data to analyze and model complex phenotypes, however, remains a challenge. Here, a new analytic approach is described, termed coreferentiality, together with an appropriate statistical test. Coreferentiality is the indirect relation of two variables of functional interest in respect to whether they parallel each other in their respective relatedness to multivariate reference data, which can be informative for a complex effect or phenotype. It is shown that the power of coreferentiality testing is comparable to multiple regression analysis, sufficient even when reference data are informative only to a relatively small extent of 2.5%, and clearly exceeding the power of simple bivariate correlation testing. Thus, coreferentiality testing uses the increased power of multivariate analysis, however, in order to address a more straightforward interpretable bivariate relatedness. Systematic application of this approach could substantially improve the analysis and modeling of complex phenotypes, particularly in the context of human study where addressing functional hypotheses by direct experimentation is often difficult.

A hipertensão arterial e os fatores socioculturais em pessoas adultas do município de Tanque D’arca

A pressão arterial (PA) é definida fisiologicamente de acordo com diversos fatores próprios e ambientais. Fatores fisiológicos próprios como etnia, idade, sexo e genéti-ca familiar podem influenciar inteiramente nos valores da PA de um indivíduo. Os problemas multifatoriais que podem elevar os níveis da pressão arterial sistémica - HAS de um indivíduo são: a obesidade, a diabetes, o tabagismo, o etilismo, o seden-tarismo, o estresse, o uso excessivo de sal na dieta, e o uso de anticoncepcionais orais. Este estudo teve por objetivo investigar quais os principais fatores que se tor-naram determinantes para um índice elevado de hipertensos no município de Tan-que D’arca nos últimos 10 anos. Este estudo é transversal, com uma amostra de 376 indivíduos entre 20 e 90 anos ou mais, acompanhados nas unidades básicas de sa-úde do município. E após a analise dos dados colhidos através de questionários foi possível determinar que os fatores socioculturais estão diretamente relacionados com o elevado número de casos de hipertensos presentes no município. Palavra-chave: Hipertensão, Uso excessivo de sal, Situação Sociocultural, Prevenção.

Quantificação e caracterização fenotípica e funcional das células NK do sangue periférico em lúpus eritematoso sistémico (LES)

Introdução: O Lúpus Eritematoso Sistémico (LES) é uma doença inflamatória crónica auto-imune que afecta múltiplos órgãos. A sua etiologia é multifactorial, em que a interacção entre factores genéticos, hormonais, ambientais e infecciosos leva à perda de tolerância imunológica e à produção de auto-anticorpos dirigidos principalmente contra antigénios nucleares, alguns dos quais participam nas lesões teciduais. As células NK através das suas capacidades citotóxicas e produção de citocinas inflamatórias podem influenciar as doenças auto-imunes. Objectivos: O objectivo deste estudo foi quantificar e analisar as características imunofenotípicas e funcionais das duas principais subpopulações de células NK nos pacientes com LES. Material e Métodos: Este estudo incidiu numa população de 44 indivíduos com diagnóstico de LES, dos quais 18 se encontravam na fase activa e 26 na fase inactiva da doença e em 30 indivíduos saudáveis, que constituíram o grupo controlo. Para este universo populacional, foi estudada a percentagem (%) e número absoluto de células NK, assim como das suas duas subpopulações, CD56dim e CD56bright, no sangue periférico e a frequência com que estes dois grupos celulares expressam o antigénio CD57 e o receptor de quimiocina CXCR3, e produzem interferon-gama (IFN- γ), factor de necrose tumoral-alfa (TNF- α), granzima B e perforina, assim como a quantidade de proteína por célula (MIF - média de intensidade de fluorescência), por citometria de fluxo. Resultados: Os resultados obtidos revelam uma clara diminuição dos números absolutos e relativos de células NK nos doentes com LES, principalmente naqueles com doença activa, enquanto que as proporções dos subtipos de células NK, não foram afectadas. Nos pacientes com LES activo encontrámos uma baixa densidade de CXCR3 em ambos os subtipos de células NK e uma baixa frequência de células NK CD56dim a expressar CXCR3. Para além disso, observámos que a expressão de granzima B nos dois grupos de doentes com LES está diminuída mas a percentagem de células NK a expressar granzima B e perforina está aumentada, especialmente na doença activa. Observou-se uma diminuição na percentagem de células NK CD56dim e CD56bright a produzir TNF- α e na sua expressão nas células NK CD56dim na doença activa, enquanto que a expressão de IFN- γ nas células NK CD56bright está aumentada em todos os pacientes com LES. Conclusão: Os nossos resultados sugerem que as células NK apresentam alterações funcionais e fenotípicas únicas, que são particularmente evidentes na doença activa, e podem afectar o desenvolvimento da doença.

Relação da imunoglobulina-A e a prevalência de cáries em crianças

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Prevalência de agenesia de terceiros molares na clínica universitária Egas Moniz

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Risco global cardiovascular

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Effets d’un programme de promotion de la vitalité cognitive sur la pratique d’activité physique d’ainés

Introduction : Plusieurs études ont démontré que la pratique d’activité physique (AP) peut avoir un impact sur la vitalité cognitive des ainés. Le programme Musclez vos Méninges encourage les participants à être davantage actif et a été conçu pour promouvoir la vitalité cognitive. Ce mémoire vise à explorer : 1) les effets du programme sur l’AP; 2) l’effet modérateur et médiateur de l’AP sur les impacts du programme sur la cognition; 3) la corrélation entre l’AP et certaines dimensions cognitives des participants à l’entrée dans l’étude. Méthodologie: Au total, 294 personnes âgées de 60 ans et plus, intéressées à participer à un programme de vitalité cognitive ont été recrutées. Elles ont été évaluées avec des tests cognitifs (MoCA, MIA, CVLT, RBMT, MMQ, Attention, Stroop) et des instruments sur l’AP (une version adaptée du CHAMPS et le test de marche de 2 minutes du SFT). Des corrélations ont été faites à l’entrée dans l’étude et des régressions multivariées ont été réalisées pour mesurer l’impact du programme et celui de l’AP. Résultats : La participation au programme est associée à une hausse de l’AP (p< 0,05). Les analyses n’indiquent cependant pas d’effet significatif (p< 0,05) modérateur ou médiateur. À l'entrée dans l'étude, les sujets les plus actifs présentent de meilleurs résultats pour le recours aux stratégies mnésiques (p< 0,05). Conclusion: Un programme multifactoriel, incluant la promotion de l’AP, peut modifier significativement l’engagement à être physiquement actif. Des études futures devront toutefois démontrer si la pratique d’AP peut avoir un effet modérateur ou médiateur sur la vitalité cognitive.

The Effect of Fructose vs. Glucose Beverages on Low-Grade Systemic Inflammation

Thesis (Ph.D.)--University of Washington, 2016-04

Correlates of depressive symptoms in a representative sample of young Australian women

This paper presents a descriptive analysis of the prevalence of depressive symptoms among a national cohort of young Australian women, and the characteristics of those who experience them. It explores the associations between demographic and health-related variables and depressive symptoms in a representative sample of 9333 Australian women aged 22-27 years, from the Australian Longitudinal Study on Women's Health. Approximately 30% of these young women indicated that they were experiencing depressive symptoms, as indicated by the Center for Epidemiological Studies Depression Scale (CESD-10). After adjusting for age and rurality of residence, depressive symptoms were related to the following demographic variables: low income, low educational qualifications, a history of unemployment, not being in a relationship, and living arrangements other than living with a partner. Those health-related variables that were significantly associated with depressive symptoms included frequent visits to doctors and medical specialists, and a higher number of physical symptoms experienced and diagnoses made. More illicit drug use, higher use of cigarettes and alcohol, and lower exercise status were also significantly associated with depressive symptoms. This analysis supports the view that depression is one aspect of a multifactorial cluster of negative conditions across several domains of functioning, including physical ill-health, risky behaviours, and marginal social status. The complex interactions between these conditions, of which depression is only one, underscore the difficulties that arise in the treatment of depression and support the value of preventive interventions as an important public health strategy.

Association between clinician factors and a patient's wish to hasten death: Terminally ill cancer patients and their doctors

This study investigated the clinical factors associated with a wish to hasten death among patients with advanced cancer receiving palliative care, with a focus on the role of clinician-related factors. Patients were grouped into high- and low-scoring groups on the basis of their wish to hasten death; doctor-patient pairs were formed. Questionnaire data collected from patients and their treating doctors were subjected to multivariate analysis. Significant predictors of a high wish to hasten death in terminally ill patients from among treating clinicians included the clinician's perception of the patient's lower optimism and greater emotional suffering, the patient indicating a wish to hasten death, the doctor willing to assist the patient in hastening death (if requested and legal), and the doctor reporting less training in psychotherapy. When these variables were combined with patient factors identified in a previous study, the model significantly predicted a wish to hasten death with the following variables patient factors: a higher perceived burden on others, higher depressive symptom scores, and lower family cohesion; physician factors: the doctor willing to assist the patient in hastening death (if requested and legal), the doctor's perception of lower levels of optimism and greater emotional distress in the patient, and the doctor having less training in psychotherapy; and the setting of care: recent admission to a hospice. The findings support the multifactorial influences on the wish to hasten death and suggest that the role of the clinician is a vital context within which the wish to hasten death should be considered.

The TAF5L gene on chromosome 1q42 is associated with type 1 diabetes in Russian affected patients

Type 1 diabetes (T1D) is a multifactorial autoimmune disease, with strong genetic component. Several susceptibility loci contribute to genetic predisposition to T1D. One of these loci have been mapped to chromosome 1q42 in UK and US joined affected family data sets but needs to be replicated in other populations. In this study, we evaluated sixteen microsatellites located on 1q42 for linkage with T1D in 97 Russian affected sibling pairs. A 2.7-cm region of suggestive linkage to T1D between markers D1S1644 and D1S225 was found by multipoint linkage analysis. The peak of linkage was shown for D1S2847 (P = 0.0005). Transmission disequilibrium test showed significant undertransmission of the 156-bp allele of D1S2847 from parents to diabetic children (28 transmissions vs. 68 nontransmissions, P = 0.043) in Russian affected families. A preferential transmission from parents to diabetic offspring was also shown for the T(-25) and T1362 alleles of the C/T(-25) and C/T1362 dimorphisms, both located at the TAF5L gene, which is situated 103 kb from D1S2847. Together with the A/C744 TAF5L SNP, these markers share common T(-25)/A744/T1362 and C(-25)/C744/T1362 haplotypes associated with higher and lower risk of diabetes (Odds Ratio = 2.15 and 0.62, respectively). Our results suggest that the TAF5L gene, encoding TAF5L-like RNA polymerase II p300/CBP associated factor (PCAF)-associated factor, could represent the susceptibility gene for T1D on chromosome 1q42 in Russian affected patients.

A comparison of the Yale-Brown obsessive compulsive scale for "Heavy drinking" with a single item craving measure: Construct validity and clinical utility

The measurement of alcohol craving began with single-item scales. Multifactorial scales developed with the intention to capture more fully the phenomenon of craving. This study examines the construct validity of a multifactorial scale, the Yale-Brown Obsessive Compulsive Scale for heavy drinking (Y-BOCS-hd). The study compares its clinical utility with a single item visual-analogue craving scale. The study includes 212 alcohol dependent subjects (127 males, 75 females) undertaking an outpatient treatment program between 1999-2001. Subjects completed the Y-BOCS-hd and a single item visual-analogue scale, in addition to alcohol consumption and dependence severity measures. The Y-BOCS-hd had strong construct validity. Both the visual-analogue alcohol craving scale and Y-BOCS-hd were weakly associated with pretreatment dependence severity. There was a significant association between pretreatment alcohol consumption and the visual-analogue craving scale. Neither craving measure was able to predict total program abstinence or days abstinent. The relationship between obsessive-compulsive behavior in alcohol dependence and craving remains unclear.