Text in English / Two consecutive referrals of early onset (symptom onset at 11 years) anorexia nervosa (restricting sub-type) to an inpatient eating disorders unit in a psychiatric hospital, will be described. Within both cases, there was a history of sequential mother-daughter dieting prior to the daughter's onset of anorexic symptoms. This pattern will be viewed from the perspective of systemic theory, with reference to the cybernetic processes implicated in the onset and maintenance of symptoms. Structural systemic interpretations, in terms of exchangeable senses of self within the mother-daughter pairs, will also be considered. A brief comment will be made about the symmetry which underlies the choreography of anorexia nervosa when viewed from the perspective of communication theory. The implications for intervention will be addressed. In conclusion, the nature of the intergenerational transmission of disordered eating behaviours, will be considered with reference to the nature-nurture debate. / Clinical Psychology / M.A. (Clinical Psychology)

Background. This study sought to determine the distribution of early-onset restrictive eating disturbances characteristic of the new DSM-5 diagnosis, avoidant/restrictive food intake disorder (ARFID) in middle childhood, as well as to evaluate the screening instrument, Eating Disturbances in Youth-Questionnaire (EDY-Q). Methods. A total of 1444 8- to 13-year-old children were screened in regular schools (3rd to 6th grade) in Switzerland using the self-report measure EDY-Q, consisting of 12 items based on the DSM-5 criteria for ARFID. Results. Forty-six children (3.2%) reported features of ARFID in the self-rating. Group differences were found for body mass index, with underweight children reporting features of ARFID more often than normal- and overweight children. The EDY-Q revealed good psychometric properties, including adequate discriminant and convergent validity. Conclusions. Early-onset restrictive eating disturbances are commonly reported in middle childhood. Because of possible negative short- and long-term impact, early detection is essential. Further studies with structured interviews and parent reports are needed to confirm this study’s findings.

Smith-Magenis syndrome (SMS) is a complex disorder caused by haploinsufficiency of RAI1 and characterized by sleep disturbances, behavioral abnormalities, mental retardation, and obesity in teens and adults. Rai1+/- mice are obese after 20 weeks. Dup(17)(p11.2) syndrome is a complex disorder associated with overexpression of RAI1. A transgenic mouse model of dup(17)(p11.2) syndrome overexpresses Rai1 and results in a mouse that is growth delayed. In order to characterize the obese phenotypes of mouse models of SMS and the role of RAI1 in obesity, daily food intake and serum levels of insulin, glucose, PPY, and leptin were measured; adiposity was studied by characterizing fat deposition; and gene expression was studied in the hypothalamus. These studies show that Rai1+/- mice are hyperphagic, consume more during the inactive light phase, and have altered satiety genes in the hypothalamus. Adiposity studies have shown WT females have a higher body fat content and visceral fat proportion than males, but Rai1-Tg and Rai1+/- females have similar fat deposition patterns as WT males. Hypothalamic gene expression studies show that many genes and pathways are affected by Rai1 and Rai1 dosage, including many genes associated with obesity and satiety.

Affectant plus de 1% de la population, les troubles bipolaires constituent l'une des maladies mentales les plus fréquentes, sévères et dévastatrices. Ces troubles de l’humeur se caractérisent par une alternance d’épisodes maniaques (humeur exaltée, euphorie, irritabilité) et d’épisodes dépressifs, entrecoupés de phases de rémission. Malgré une composante génétique démontrée, les études génétiques peinent à identifier des gènes de vulnérabilité à cause de facteurs environnementaux et d’une hétérogénéité génétique, sous-tendue par une forte hétérogénéité clinique. Une analyse de liaison sur l’ensemble du génome de 87 paires de germains atteints de trouble bipolaire à début précoce, sous-groupe cliniquement homogène de patients, a révélé des liaisons suggestives avec les régions chromosomiques 3p14 et 20p12. Un variant fonctionnel dans le promoteur du gène SNAP25, situé en 20p12, est associé au trouble bipolaire à début précoce. Ce gène code une protéine essentielle à la libération de neurotransmetteurs. Nous avons étudié 2 gènes candidats à la vulnérabilité au trouble bipolaire à début précoce, localisés dans la région 3p14, SYNPR et CADPS, codant des partenaires de SNAP25. Nous avons identifié des mutations non-synonymes et une délétion dans CADPS, chez 4,5% des patients, suggérant son implication dans la vulnérabilité aux troubles bipolaires et suggérant une hétérogénéité génétique. Une recherche de micro-remaniements chromosomiques a identifié sept nouveaux gènes candidats aux troubles bipolaires : NRXN1, LINGO2, CDH8, ANKS1b, GPHN, PLCXD3 et GABARAPL1. Les protéines codées sont impliquées dans la transmission synaptique. Ces résultats font concevoir une modification de la fonction synaptique dans la vulnérabilité génétique des troubles bipolaires. Ces études permettront, à plus long terme, une meilleure compréhension de la physiopathologie des troubles bipolaires et peut-‐être d’identifier des biomarqueurs de ces troubles. Elles devraient également permettre d’ouvrir de nouvelles voies d’exploration pour les stratégies thérapeutiques. / Bipolar Affective Disorder (BPAD) is a common, severe and fatal psychiatric disease, affecting approximately 1% of general population. Despite a demonstrated genetic component, genetic studies have difficulties in identifying vulnerability genes, because of environnemental effects, clinic heterogenity and genetic heterogeneity. We performed a linkage study in 87 sib-­‐pairs with early-­‐onset bipolar affective disorder type I probands, which reported suggestive linkage in 3p14 and 20p12. Functional variant in SNAP25 promotor, located in 20p12 is associated with early-­‐onset BPAD. This gene encodes essential protein implicated in neurotransmitters release. We studied two candidate genes for vulnerability to BPAD, SYNPR and CADPS, located in 3p14, encoding SNAP25 cellular partners. We reported patient-­‐specific non-­‐synonymous variants and a 9kb coding deletion in 4,5% of patients, for CADPS gene, suggesting its implication in vulnerability to BPAD. We enlarged these findings by genome wide search for Copy Number Variants. We choosed 7 variants affecting synaptic genes: NRXN1, LINGO2, CDH8, ANKS1b, GPHN, PLCXD3 and GABARAPL1 as new candidate genes for BPAD. These findings suggested a modified synaptic function in bipolar patients. These studies would allowed a better understanding of pathophysiology of bipolar affective disorder and could open new ways of diagnostic, preventive and therapeutic strategies.

Objective: This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Method: Using the EDY-Q, a total of 1444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). Results: The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. Discussion: The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews.

La thèse a pour objectifs d'identifier les besoins et les difficultés des conjoints aidants de personnesprésentant une maladie d'Alzheimer. Elle vise également à mettre en évidence les points communs etles spécificités de la situation d’aide en fonction de l’âge d’apparition de la maladie. L’axe 1 porte sur l’analyse du vécu de couples dont l'un des partenaires présente une démence précoce. Les résultats mettent en évidence une évolution dans le rapport au savoir des aidants et des personnes malades. Ils passent d'un besoin de comprendre les changements occasionnés par l’arrivée de la maladie à une mise à distance après l'annonce du diagnostic. De plus, avec l'avancée des troubles, les aidants éprouvent des difficultés à ajuster leur niveau d’aide, ce qui est source de conflits entre les deux partenaires. Les deux études de l'axe 2 ont pour objectif d’établir une comparaison entre les aidants de personnes malades jeunes et de personnes malades âgées à la fois sur leurs besoins et sur leurs modes d’ajustement. La majorité des besoins et des stratégies est commune à tous les aidants. Néanmoins, les aidants de personnes malades jeunes expriment plus de besoins en termes de maintien de contact, d'adaptation des structures de soins et d'accompagnement dans les démarches administratives. Les aidants de personnes malades âgées utilisent plus l'humour, l'aménagement et la mise à distance de l'entourage comme stratégies d'ajustement. L’axe 3 vise à investiguer l'influence des caractéristiques de la situation d'aide sur la détresse du conjoint aidant à l’aide d’une modélisation structurale. Les paramètres de ce modèle général ont été comparés en fonction de l'âge de début de la maladie et du genre de l'aidant. Cette étude met en évidence 4 facteurs influençant le sentiment de détresse des conjoints aidants : le sentiment d'être préparé, la qualité du support familial, l’évaluation de sa santé et la qualité d’ajustement du couple. Ce dernier facteur est plus important pour les conjoints aidants de personnes malades jeunes. L’analyse de ces résultats permet de spécifier le contenu de programmes d’accompagnement en faveur de modules communs à tous les aidants et de modules spécifiques en fonction de l'âge d'apparition de la maladie. / This thesis aims to identify needs and difficulties of the spouse caregivers of persons with dementia. We also investigate similarities and specificities related to the caregiving situation regarding the age atonset of the disease.The first axis examines the experience of couples in which one member received a diagnosis of earlyon setdementia. The results show an evolution in the relation to knowledge of the caregivers and the persons with dementia. They oscillate between the need to understand the changes caused by the disease and a distancing after the diagnosis. Moreover, with the progression of the disease, the caregivers are not able to adapt their level of assistance, which increases tensions between the two partners. The two studies of the second axis aim to compare needs and coping strategies of spouse caregivers of persons with early and late onset dementia. The majority of needs and strategies are the same for all spouse caregivers. However, the spouse caregivers of persons with early-onset dementia express the greatest number of needs related to maintaining contacts, more need of adapted care structures and more need to be assisted in administrative procedures. The spouse caregivers of persons with late-onset dementia use more humor, re-arranging, and getting away from the entourage. The third axis investigates the influence of the characteristics of the caregiving context on spousal caregiver distress with a structural modelisation. The sittings of this general model were compared regarding the age at onset of the disease and the gender of caregiver. This study demonstrated that 4 factors contribute to spousal caregiver distress: preparedness, family support, self-rated health and the quality of the couple relationship. Dyadic determinants were more important for caregivers of PEOD. The analysis of these results permits to specify the content of support for a common core and specific modules depending on the age at onset of the disease.

Introdução: as infecções são responsáveis por mais de um terço das mortes neonatais, sendo a sepse a de maior expressão. A sepse neonatal precoce (SNP) aumenta em cinco vezes a taxa de mortalidade entre recém-nascidos (RN) de termo e pré-termos tardios e em vinte e cinco vezes a taxa de mortalidade entre pré-termos extremos. A Variabilidade da Frequência Cardíaca (VFC) vem se mostrando capaz de antecipar o diagnóstico, reduzindo em 22% o risco relativo de mortalidade entre os pré-termos de muito baixo peso com sepse. Objetivo: verificar a VFC de RN com suspeita de SNP; identificar medidas significantes e verificar se, associadas a variáveis clínico-laboratoriais, aumentam a chance de identificar pacientes passíveis de desenvolver a doença. Método: utilizou-se um frequencímetro portátil para aferir as medidas da VFC nos domínios do tempo, da frequência e do Caos. Dentre elas, elegeu-se aquelas com curva ROC > 0,75 para, com seus valores de cut-off, aplicar regressão logística e identificar as que melhor se adequassem ao modelo. As variáveis clínico-laboratoriais significantes que restaram da análise univariada foram submetidas à análise multivariada a fim de identificar, também, as que melhor se adequassem ao modelo. Resultados: foram identificadas quatro variáveis clínico-laboratoriais (sexo masculino, idade gestacional < 34 semanas, Score de Rodwell e proteína C-reativa), e nove medidas da VFC (RRmean, SDNN, RR tri index, LF, HF, SD2 do plot de Poincaré, ShaEnt, CorrDim D2 e SamAsy). Cinco apresentaram área sob a curva ROC > 0,75: SDNN, RR tri index, LF, SD2 e CorrDim D2. Depois de aplicada a regressão logística, restou apenas a CorrDim D2 com cut-off = 0,1164. Identificadas, as variáveis foram submetidas ao cálculo do logit para, com isso, quantificar a chance do paciente suspeito de evoluir para a doença, na dependência das três variáveis eleitas: CorrDim D2, idade gestacional < 34 semanas e score de Rodwell. Conclusão: o estudo mostrou que tanto o modelo preditivo clinico como a CorrDim D2 são capazes, de forma independente, de estimar a chance que um futuro paciente com sepse suspeitada tem de efetivamente confirmar o diagnóstico de sepse. E que, além disso, se a CorrDim D2 for agregada ao modelo preditivo clínico, esta chance aumenta consideravelmente. / Introduction: infectious diseases are responsible for more than one-third of neonatal deaths, and sepsis is of great importance. Early Neonatal Sepsis (ENS) increases five times the mortality rate among term and late preterm newborns. Among extreme preterm babies the mortality rate increases by twenty-five times. Heart Rate Variability (HRV) has been showing to be capable of anticipating the diagnosis, thus reducing by 22 percent the relative risk of mortality of very low preterm babies with sepsis. Objective: to verify HRV of newborn babies suspects of having ENS; to identify significant measures of HRV and to verify if, associated to clinical-laboratorial variables, if they improve the chance of identifying patients exposed to developing ENS. Method: a portable frequencimeter was used to registering the measurements of HRV in the domains of time, of frequency and of chaos. Among them, only those with a ROC curve greater than 0.75 were chosen, with their cut-off values to enter a logistic regression with the aim of identifying those more suitable to the model. The clinical-laboratorial variables which were considered significant in a univariete analysis were also submitted to the multivariate analysis with the purpose of identifying those better fitted to the model. Results: four clinical-laboratorial variables (male sex, gestational age less than 34 weeks, the Rodwell Score and C-Reactive Protein); similarly, nine measures of HRV (RRmean, SDNN, RR tri index, LF, HF, SD2 of Poincaré plot, ShaEnt, CorrDimD2 and SamAsy). Five of them presented an area under the ROC curve greater than 0.75: SDNN, RR tri index, LF, SD2 and CorrDim D2. Once applied the logistic regression, only CorrDim D2 remained, with a cut-off value of 0.1164. The identified variables were, then, submitted to the calculation of the logit, with the purpose of quantifying the chance of a patient suspect of evolving to a sepsis, in the dependence of the three elected variables: CorrDim D2, gestational age under 34 weeks and the Score of Rodwell. Conclusion: the study showed that both, the predictive clinical model as CorrDim D2 are able, independently, to estimate the chance that a patient with suspected sepsis future has to effectively confirm the diagnosis of sepsis. And that, moreover, if the CorrDim D2 is aggregated to clinical predictive model, this chance increases considerably.

Introdução: as infecções são responsáveis por mais de um terço das mortes neonatais, sendo a sepse a de maior expressão. A sepse neonatal precoce (SNP) aumenta em cinco vezes a taxa de mortalidade entre recém-nascidos (RN) de termo e pré-termos tardios e em vinte e cinco vezes a taxa de mortalidade entre pré-termos extremos. A Variabilidade da Frequência Cardíaca (VFC) vem se mostrando capaz de antecipar o diagnóstico, reduzindo em 22% o risco relativo de mortalidade entre os pré-termos de muito baixo peso com sepse. Objetivo: verificar a VFC de RN com suspeita de SNP; identificar medidas significantes e verificar se, associadas a variáveis clínico-laboratoriais, aumentam a chance de identificar pacientes passíveis de desenvolver a doença. Método: utilizou-se um frequencímetro portátil para aferir as medidas da VFC nos domínios do tempo, da frequência e do Caos. Dentre elas, elegeu-se aquelas com curva ROC > 0,75 para, com seus valores de cut-off, aplicar regressão logística e identificar as que melhor se adequassem ao modelo. As variáveis clínico-laboratoriais significantes que restaram da análise univariada foram submetidas à análise multivariada a fim de identificar, também, as que melhor se adequassem ao modelo. Resultados: foram identificadas quatro variáveis clínico-laboratoriais (sexo masculino, idade gestacional < 34 semanas, Score de Rodwell e proteína C-reativa), e nove medidas da VFC (RRmean, SDNN, RR tri index, LF, HF, SD2 do plot de Poincaré, ShaEnt, CorrDim D2 e SamAsy). Cinco apresentaram área sob a curva ROC > 0,75: SDNN, RR tri index, LF, SD2 e CorrDim D2. Depois de aplicada a regressão logística, restou apenas a CorrDim D2 com cut-off = 0,1164. Identificadas, as variáveis foram submetidas ao cálculo do logit para, com isso, quantificar a chance do paciente suspeito de evoluir para a doença, na dependência das três variáveis eleitas: CorrDim D2, idade gestacional < 34 semanas e score de Rodwell. Conclusão: o estudo mostrou que tanto o modelo preditivo clinico como a CorrDim D2 são capazes, de forma independente, de estimar a chance que um futuro paciente com sepse suspeitada tem de efetivamente confirmar o diagnóstico de sepse. E que, além disso, se a CorrDim D2 for agregada ao modelo preditivo clínico, esta chance aumenta consideravelmente. / Introduction: infectious diseases are responsible for more than one-third of neonatal deaths, and sepsis is of great importance. Early Neonatal Sepsis (ENS) increases five times the mortality rate among term and late preterm newborns. Among extreme preterm babies the mortality rate increases by twenty-five times. Heart Rate Variability (HRV) has been showing to be capable of anticipating the diagnosis, thus reducing by 22 percent the relative risk of mortality of very low preterm babies with sepsis. Objective: to verify HRV of newborn babies suspects of having ENS; to identify significant measures of HRV and to verify if, associated to clinical-laboratorial variables, if they improve the chance of identifying patients exposed to developing ENS. Method: a portable frequencimeter was used to registering the measurements of HRV in the domains of time, of frequency and of chaos. Among them, only those with a ROC curve greater than 0.75 were chosen, with their cut-off values to enter a logistic regression with the aim of identifying those more suitable to the model. The clinical-laboratorial variables which were considered significant in a univariete analysis were also submitted to the multivariate analysis with the purpose of identifying those better fitted to the model. Results: four clinical-laboratorial variables (male sex, gestational age less than 34 weeks, the Rodwell Score and C-Reactive Protein); similarly, nine measures of HRV (RRmean, SDNN, RR tri index, LF, HF, SD2 of Poincaré plot, ShaEnt, CorrDimD2 and SamAsy). Five of them presented an area under the ROC curve greater than 0.75: SDNN, RR tri index, LF, SD2 and CorrDim D2. Once applied the logistic regression, only CorrDim D2 remained, with a cut-off value of 0.1164. The identified variables were, then, submitted to the calculation of the logit, with the purpose of quantifying the chance of a patient suspect of evolving to a sepsis, in the dependence of the three elected variables: CorrDim D2, gestational age under 34 weeks and the Score of Rodwell. Conclusion: the study showed that both, the predictive clinical model as CorrDim D2 are able, independently, to estimate the chance that a patient with suspected sepsis future has to effectively confirm the diagnosis of sepsis. And that, moreover, if the CorrDim D2 is aggregated to clinical predictive model, this chance increases considerably.

Submitted by Vanessa Rocha Ribeiro null (va_rocharibeiro@aluno.ibb.unesp.br) on 2017-03-08T15:02:28Z No. of bitstreams: 1 Dissertação Vanessa Rocha Ribeiro.pdf: 3324263 bytes, checksum: c662d084e05ff3055723d93ba4f2eee2 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-03-13T14:49:32Z (GMT) No. of bitstreams: 1 ribeiro_vr_me_bot.pdf: 3324263 bytes, checksum: c662d084e05ff3055723d93ba4f2eee2 (MD5) / Made available in DSpace on 2017-03-13T14:49:32Z (GMT). No. of bitstreams: 1 ribeiro_vr_me_bot.pdf: 3324263 bytes, checksum: c662d084e05ff3055723d93ba4f2eee2 (MD5) Previous issue date: 2017-02-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Introdução: A pré-eclâmpsia (PE) é uma patologia obstétrica e uma das principais causas de morbimortalidade materna e fetal. Na PE ocorre um estado de má adaptação da tolerância imunológica, caracterizada por ativação anormal do sistema imune inato e adaptativo. As células T reguladoras (Treg) representam uma população de linfócitos T responsáveis pela manutenção da tolerância e controle da inflamação, enquanto células Th17 medeiam diferentes tipos de reações inflamatórias. Portanto, o balanço entre células Treg e Th17 pode ser crítico para a tolerância ao feto e prevenção da PE. Objetivo: Avaliar as subpopulações de células T CD4+ (Th1, Th2, Th17 e Treg) e o perfil de citocinas produzido por essas células, em gestantes portadoras de pré-eclâmpsia, classificadas em PE precoce e PE tardia. Métodos: Foram estudadas 60 gestantes, sendo 20 normotensas e 40 portadoras de PE, pareadas pela idade gestacional. As gestantes com PE foram classificadas de acordo com o aparecimento das manifestações clínicas em PE precoce (< 34 semanas de gestação; n=20) e PE tardia (≥ 34 semanas de gestação; n=20). Células mononucleares do sangue periférico (PBMCs), obtidas das gestantes foram avaliadas quanto à produção de citocinas pró e anti-inflamatórias e à expressão de fatores de transcrição envolvidos na caracterização das subpopulações de células T CD4+. A expressão dos fatores de transcrição intracitoplasmáticos de células Th1 (T-bet), Th2 (GATA-3), Th17 (RORc) e Treg (FoxP3) foi avaliada por citometria de fluxo e a expressão gênica desses fatores de transcrição foi determinada por PCR em tempo real com transcrição reversa (RT-qPCR), logo após a colheita de sangue para avaliação da expressão endógena dessas diferentes subpopulações de células T. A determinação das citocinas de perfil Th1 (IFN-γ e TNF-α), Th2 (IL-4), Th17 (IL-6, IL-17 e IL-22) e Treg (IL-10 e TGF-β1) foi realizada no plasma das gestantes pela técnica de ELISA. Os resultados foram analisados por meio de testes paramétricos ou não paramétricos com nível de significância de 5%. Resultados: Os perfis inflamatórios Th1 e Th17 foram identificados por aumento significativo da média de intensidade de fluorescência (MIF) e da percentagem de células expressando os fatores de transcrição específicos nas gestantes portadoras de PE precoce e PE tardia em relação aos grupos de gestantes normotensas com idade gestacional correspondente. A percentagem de células Th17 foi significativamente maior nas gestantes com PE precoce do que nas com PE tardia. Por outro lado, a análise dos perfis anti-inflamatórios Th2 e Treg mostrou que a percentagem de células expressando GATA-3 e FoxP3 foi significativamente menor nos grupos de PE precoce e PE tardia comparados aos grupos de normotensas, enquanto a comparação entre gestantes pré-eclâmpticas mostrou percentagem de células Treg significativamente menor nas gestantes portadoras de PE precoce. A expressão gênica do fator de transcrição T-bet por PBMCs não mostrou diferenças significativas entre os grupos de gestantes pré-eclâmpticas e de normotensas. Aumento significativo da expressão gênica do fator de transcrição RORc e diminuição da expressão dos genes GATA-3 e FoxP3 foram observados nos grupos de gestantes pré-eclâmpticas em relação aos grupos de normotensas de idade gestacional correspondente. Entre as gestantes pré-eclâmpticas, encontrou-se menor nível transcricional do fator de transcrição GATA-3 na PE precoce. Os níveis plasmáticos das citocinas IFN-γ, IL-6, IL-17 e TNF-α foram significativamente maiores nas gestantes portadoras de PE, enquanto as concentrações de IL-10 e TGF-β1 foram significativamente menores em comparação aos grupos de gestantes normotensas correspondentes. Observaram-se ainda, maiores níveis de IL-6, IL-17, TGF-β1 e TNF-α na PE precoce do que na PE tardia. A expressão proteica de IL-4 (perfil Th2) e IL-22 (perfil Th17), não apresentou diferença significativa entre os grupos estudados. Conclusão: Os resultados demonstram que o balanço entre células Treg e Th17 é deficiente na PE, havendo polarização para perfil Th17 na PE precoce. Esse desbalanço pode ser atribuído ao predomínio de citocinas pró-inflamatórias sobre as anti-inflamatórias, presentes na circulação de gestantes portadoras de pré-eclâmpsia. / Introduction: Preeclampsia (PE) is an obstetric pathology and one of the main causes of maternal and fetal morbidity and mortality. In PE there is a state of maladaptation of immunological tolerance, characterized by abnormal activation of the innate and adaptive immune system. Regulatory T cells (Treg) represent a population of T lymphocytes responsible for tolerance maintenance and inflammation control, whereas Th17 cells mediate different types of inflammatory reactions. Therefore, the balance between Treg and Th17 cells may be critical for fetal tolerance and PE prevention. Objective: To evaluate the subpopulations of CD4+ T cells (Th1, Th2, Th17 and Treg) and the cytokine profile produced by these cells in pregnant women with PE, classified in early-onset PE and late-onset PE. Methods: Sixty pregnant women, 20 normotensive and 40 preeclamptic women, matched by gestational age, were studied. Pregnant women with PE were classified according to clinical manifestations in early-onset PE (<34 weeks gestation; n = 20) and late-onset PE (≥ 34 weeks gestation; n = 20). Peripheral blood mononuclear cells (PBMCs) obtained from pregnant women were evaluated for the production of pro and anti-inflammatory cytokines and expression of transcription factors involved in the characterization of CD4+ T cell subpopulations. Expression of the intracytoplasmic transcription factors of Th1 (T-bet), Th2 (GATA-3), Th17 (RORc) and Treg (FoxP3) cells was assessed by flow cytometry and the gene expression of these transcription factors was determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) shortly after blood collection to evaluate the endogenous expression of these different T-cell subpopulations. The cytokine profile of Th1 cells (IFN-γ and TNF-α), Th2 (IL -4), Th17 (IL-6, IL-17 and IL-22) and Treg (IL-10 and TGF-β1) were measured in the plasma of the pregnant women by the ELISA. The results were analyzed using parametric or non-parametric tests with a significance level of 5%. Results: Th1 and Th17 inflammatory profiles were identified by a significant increase in mean fluorescence intensity (FMI) and by the percentage of cells expressing specific transcription factors in pregnant women with early-onset PE and late-onset PE in relation to the normotensive groups with corresponding gestational age. The percentage of Th17 cells was significantly higher in early-onset PE than in late-onset PE group. On the other hand, analysis of Th2 and Treg anti-inflammatory profiles showed percentages of cells expressing GATA-3 and FoxP3 significantly lower in the early- and late-onset PE groups compared to the normotensive groups, whereas the comparison between preeclamptic groups showed significantly lower percentage of Treg cells in pregnant women with early-onset PE. The gene expression of the T-bet transcription factor by PBMCs did not show significant differences between the preeclamptic and normotensive pregnant groups. Significant increase in the gene expression of RORc and decrease in the expression of the GATA-3 and FoxP3 genes were observed in both groups of preeclamptic women compared with the normotensive ones of corresponding gestational age. Among the preeclamptic pregnant women lower transcriptional level of GATA-3 transcription factor was detected in early-onset PE. Plasma levels of the cytokines IFN-γ, IL-6, IL-17 and TNF-α were significantly higher in pregnant women with PE, whereas IL-10 and TGF-β1 concentrations were significantly lower than in the normotensive corresponding groups. It was also observed higher levels of IL-6, IL-17, TGF-β1 and TNF-α in early-onset than in late-onset PE group. Protein expression of IL-4 (Th2 profile) and IL-22 (Th17 profile), did not show significant differences between the groups studied. Conclusion: The results show that the balance between Treg and Th17 cells is deficient in PE, with polarization to the Th17 profile in early-onset PE. This imbalance can be attributed to the predominance of pro-inflammatory cytokines over the anti-inflammatory ones present in the circulation of pregnant women with preeclampsia. / FAPESP: 2014/25124-7 / FAPESP: 2012/24697-8

International and national research has shown that the use of complementary therapies (often referred to in the scientific literature as either alternative therapies or unconventional therapies) is widespread. However, there is little in the scientific literature about the use of complementary therapies in the treatment regime of people with dementia. Specifically, there have been no published results of investigations into the use of Reiki, a holistic complementary therapy, in the treatment regime of people with dementia. Before proceeding with an in-depth examination into the use of Reiki in the care of people with dementia, a questionnaire containing both closed and open-ended questions was distributed to 162 South Australian High Care Residential Facilities (formerly called Nursing Homes) in 2002. The return rate was 58.0% (n=94) of which 50.0% of the mail out (n=81) was available for analysis. Findings from the questionnaires suggested that a wide range of complementary therapies including aromatherapy, massage, music, behaviour therapy, healing touch, Reiki and Therapeutic Touch (Krieger/Kunz method) were used regularly within South Australian High Care Residential Facilities. Complementary therapies were reportedly used to calm residents, improve behaviour management, enhance the quality of life of residents, promote 1:1 interaction, stimulate the senses, and reduce the need for medication. Due to 15 facilities reporting the use of Reiki, a series of semi-structured interviews with Reiki practitioners caring for people with dementia was conducted in 2004/2005. Interview participants (n=10) included a representative range of people providing care for people with dementia in eight Nursing Homes in Adelaide, South Australia. Data reduction methods included a quasi-statistical counting of key words and repeated re-readings of the transcripts to discover the essences, abstract the meanings and arrange them into themes and sub-themes. The results of the interviews suggested that Reiki is an easy to learn and easy to use holistic complementary therapy which has the potential to enhance the quality of life of the persons with dementia, their family members, and their carers. The interview participants reported improved physical, psychological, mental and emotional well-being as well as enhanced relationships and a reduction in negative behaviours following the use of Reiki. The receipt of the first Jack Loader Scholarship from the Rosemary Foundation for Memory Support Inc. in early 2005 enabled the researcher to transfer to full-time studies from April 2005. Key Words: aged care; alternative therapies; complementary therapies; dementia; early onset dementia; one to one interaction; quality of life; Reiki; therapeutic touch; unconventional therapies.