Premature ovarian Insufficiency (POI) is the cessation of the ovarian function before the age of 40, defined by high serum gonadotrophins, low estradiol and amenorrhea for at least 4 months. The etiology may be iatrogenic after a surgery, chemotherapy or radiotherapy treatment, environmental, autoimmune or genetic. However, in most of the cases the cause remains unknown. Clinical and family studies suggest a strong heritability of age at menopause and POI, but the number of genetic causes and genes identified to be involved in human POI remains very small. In POI patients, the two crucial functions of the ovary, hormonal secretion and reproduction, are absent. In the last decades, however, new advances in assisted reproduction techniques have allowed the possibility of carrying pregnancies to POI women, thanks to oocyte donation. The aim of this study was to identify new genetic factors implicated in the development of POI women and to analyse the reproductive possibilities and outcome of women with a genetic cause of POI. For the first part of the study, the DNA of a cohort of POI women recruited in the Fertility Clinic of the Hôpital Erasme of the Université Libre de Bruxelles was used to sequence five candidate genes (FSHR, GDF9, BMP15, AMH and AMHR2) known to be implicated in the ovarian folliculogenesis. The most important findings were two very rare variants and one unknown variant in the AMH gene. The functional study performed with these variants suggested a diminished function of the mutant protein. Furthermore, one of the variants was found in the mother of one of the patients, who was also diagnosed of POI at 32 years old. These arguments strongly suggest that a defective AMH could play a role in the development of POI. This is supported by previous studies with knock out mice models, which show an earlier depletion of the ovarian follicle pool due to a faster recruitment of the primordial follicles that constitute the ovarian reserve. The sequencing of the BMP15 gene led to the identification of two new variants not identified among controls but not predicted to be deleterious. Interestingly, one variant previously reported in POI women and predicted to be deleterious for the protein function, was found in a Sub-Saharan African POI patient as well as in our control cohort. This variant was already studied functionally and shown to have a reduced biological activity. However, we identified this variant in 6% of the Sub-Saharan African control population, which suggests that this is a more prevalent variant in the African genotype and raises up the importance of the ethnicity when studying genetic variants.The sequencing of the other genes (FSHR, GDF9 and AMHR2) did not lead to any association with POI.In the second part of the study, 24 women with Turner syndrome and POI were analysed in terms of reproductive, obstetrical and perinatal outcome after oocyte donation. This specific group of patients was chosen because of their specific systemic anomalies that could interfere with pregnancy outcome and because very few reports have been published on this subject. In the 23 patients finally transferred, the pregnancy rate was similar to that obtained after oocyte donation in other cohorts. There was a miscarriage rate of 23% and a rate of complications of pregnancy as high as 50%, mainly caused by pregnancy-induced hypertensive diseases. Four women at risk of genetic POI were included in the fertility preservation program in order to vitrify their oocytes. Three of them have already vitrified successfully their oocytes but none of them has yet used them.Oocyte vitrification represents a new hope for those women with genetic risk of POI to be able to carry a pregnancy with their own oocytes.In conclusion, three variants of the AMH gene could be implicated in the development of POI as demonstrated by the reduced in vitro bioactivity of the variants and the familial segregation of the cases. Since then, it sounds plausible to propose AMH sequencing in the case of familial POI and secondary amenorrhea.In the BMP15 gene, 2 new variants were predicted to be tolerated. A potentially deleterious variant of the BMP15 gene (L148P) previously associated to POI, was also found in 6% of the Sub-Saharan African controls which suggests that it is a common variant in the African ethnic. No clear association was found between the other tested candidate genes and our POI cohort.Regarding Turner’s Syndrome pregnancies, we can conclude that they are high-risk pregnancies that need of a multidisciplinary follow-up before and during pregnancy.Oocyte cryopreservation represents a new tool to be offered to women at risk of genetic POI to preserve their fertility, but not without previous genetic counselling. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

The age range at diagnosis, complexity of the condition, and sensitive nature of the issues involved in a diagnosis of Turner syndrome (TS), present specific challenges for health professionals in sharing information. Little is known about the perceived information needs of girls with TS and their parents. A flexible qualitative design, guided by the principles of symbolic interactionism was employed in this exploratory study. This design enabled meanings girls and their parents attached to TS, how they interpreted, shared and valued information to be uncovered. A purposive sample of 15 families with daughters aged 9 to 16 years were recruited from a tertiary paediatric endocrinology clinic. Girls and parents participated in a total of 27 recorded semi-structured interviews. Data were analysed using the framework approach and the constant comparative method. Analysis revealed how girls and their parents interpreted and used information within the context of their everyday experiences of living with TS. Three activities were described by families: gathering and receiving, making sense of, and using and sharing information. Throughout these activities, themes of uncertainty, normalising and identity were present. A series of tensions described by the girls and their parents illustrated diverse approaches to the management of information. Meanings assigned to TS by girls and their parents influenced when, what and how information was shared with others. Despite a wealth of information, the girls and their parents described unfulfilled information needs. The interviews were dominated by discussion of the social implications of the condition and more specifically to social functioning, puberty and infertility. Parents were the primary source of information. These findings provide a basis for developing evidence based approaches to information sharing.

Orientadores: Andrea Trevas Maciel Guerra, Roberto Benedito de Paiva e Silva / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-04T01:13:43Z (GMT). No. of bitstreams: 1 Suzigan_LigiaZuppiConceicao_M.pdf: 719674 bytes, checksum: 0fd7aced48effd8567e687fc3397c183 (MD5) Previous issue date: 2004 / Resumo: Objetivo: Identificar a percepção das pacientes com Síndrome de Turner (ST) a respeito de sua condição. Casuística e Método: Entrevistas individuais com 36 pacientes com ST entre 15 e 25 anos e mais de 2 anos de acompanhamento, abordando temas referentes ao impacto no momento do diagnóstico, compreensão a respeito da ST, seu impacto sobre a vida atual e expectativas de futuro. Resultados: Apenas 1/3 compreendeu o diagnóstico de ST imediatamente, e o sentimento associado a esse momento foi freqüentemente neutro (17) ou de preocupação (12). Cerca de 1/3 não soube explicar a etiologia da ST, não relacionou a ela os sintomas que apresenta e(ou) acredita haver cura. Em sua vida atual, embora a grande maioria declare que a ST não interfere em sua vida (2/3) e se considere feliz (3/4), em mais da metade dos casos há evidências de dificuldades de interação social e de relacionamento amoroso, baixa auto-estima, insatisfação com a aparência física, em particular a baixa estatura e sofrimento com a questão da esterilidade. Suas expectativas de futuro estão predominantemente ligadas a trabalho e estudo; mesmo estando com 19 anos, em média, uma em cada duas ainda espera crescer. Conclusão: Além da abordagem médica da ST, é fundamental que o conhecimento das pacientes a respeito dessa síndrome e as questões referentes a esterilidade, baixa estatura, auto-imagem e interações sociais sejam alvo de atenção especial e contínua a partir do momento do diagnóstico; a situação ideal seria a de atuação de um psicólogo juntamente com a equipe médica / Abstract: Objective: To identify the perception of patients with Turner syndrome (TS) about their condition. Methodology: Thirty-six women with TS, aged between 15 and 25 years and with over two years of medical follow-up, were individually interviewed about: the impact of TS at the moment of the diagnosis, their understanding of the syndrome, its effect in their current lives and their expectations for the future. Results: Only one third of the patients understood the diagnosis immediately and their feelings associated to that moment were neutral (17) or concerned (12). About one third of the interviewed women were unable to explain the etiology of TS, they have not related their symptoms with TS and/or believe there might be a cure for it. Although most say that the syndrome has no interference in their current lives (2/3) and that they consider themselves happy persons (3/4), in more than half of the interviews there are evidences of difficulties with social interactions and love relationships, low self-esteem, dissatisfaction with their physical appearances, mainly short stature, and worries about infertility. Their hopes for the future refer mainly to study and have a job; growing up expectation was mentioned by one in two of the women, in spite of their mean age of 19 years. Conclusion: Besides medical treatment, it is important that the knowledge of the patients about the syndrome and some issues as infertility, short stature, self-image and social interactions receive proper and continuous attention from the moment of the diagnosis. The ideal situation should be a joint-action of the psychologist and the medical team / Mestrado / Saude da Criança e do Adolescente / Mestre em Saude da Criança e do Adolescente

At the Third Turner Resource Network Symposium, a working group presented the results of collaborative discussions about the importance of autopsy in Turner syndrome (TS). Considerable gaps in understanding the causes of death in TS can only be closed by more frequent death investigations and autopsies. The presentation included an overview of autopsy methods, strategies for utilizing autopsy, and biobanking to address research questions about TS, and the role of palliative care in the context of autopsy. This review highlights strategies to promote autopsy and tissue donation, culminating with an action plan to increase autopsy rates in the TS community.

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This thesis explores the disfranchisement of free men of color in 1835 North Carolina through the lens of antebellum citizenship and within the context of the racial turmoil of the 1830s. Citizenship and the evolution of southern racial ideology converged in the 1835 North Carolina Constitutional Convention. On the one hand, free men of color voted, a right permitted in North Carolina for all taxpaying men regardless of race and one of the most crucial components of citizenship in the early republic and Jacksonian periods. But on the other hand, some North Carolina white slaveholders saw free people of color as instigators of slave uprisings and a threat to their social order and economic system. As convention delegates debated disfranchisement, they drew on their notions of citizenship and their fear of people of color, and a majority ultimately decided that free nonwhites did not deserve a voice in the political arena. My explanation of why delegates disfranchised free men of color is twofold. First, members of the convention supported disfranchisement because of the perceived connection between free people of color and slave violence. Disfranchisement also came about because the majority of delegates determined that political citizenship was reserved exclusively for white men, and the elimination of nonwhite suffrage in North Carolina was one of the most explicit representations of the ongoing transition of citizenship based on class to a citizenship based on race in the antebellum United States. / Master of Arts

Frederick Jackson Turner was a prominent American Historian who lived during America's Progressive Movement of the early twentieth century. Turner's most seminal piece, The Significance of the Frontier in American History, commonly referred to as The Frontier Thesis, challenged the accepted assumption that American culture stemmed from European ancestors. Turner resisted conventional wisdom that did not take into account the struggles and advances of the pioneers of the West. Turner believed the experiences of the pioneers forced them to adapt and modify their European roots, thus developing a distinct and separate culture from Europe. As a university professor, training a plethora of doctoral students in the field of history, Turner embraced the changes in educational thought of the time; including the importance of lifelong learning and the need to continually re-evaluate previously held beliefs. To Turner, a university professor's priority was to facilitate learning experiences that helped develop students into independent and competent critical thinkers. One way Turner differed from his contemporaries was the way he studied and wrote about history. Turner subscribed to the ideal that all aspects of historical events, incorporating information that set a complete context of the event itself was essential. The historiography Turner employed is considered a standard today. The Progressive Era also brought a wave of reformation in political, social and educational thought. Adult education programs began to develop throughout the nation. Adults for the first time had low cost opportunities outside of collegial studies to expand their professional expertise, literacy skills, and appreciation for art and entertainment. Adult education thinkers also began to systematically research and study ways in which adults best learn. The impetus of this study was to examine Turner's educational and career efforts juxtaposed with adult learning theory, principles and practices as an embedded university elite and active planner and participant of alternative adult education programs. As such, this study investigated Turner as an educator outside the field of adult education, who emulated the principles, practices and value structure of adult learning theory. / Ph. D.

William Turner remains an understudied figure of Reformation scholarship. He was a dedicated doctor, scientist, and Lutheran reformer. This thesis examines Turner and his place in the history of ideas. It looks closely at his three editions of A Comparison Betweene the Olde Learnynge and the Newe (1537, 1538, 1548) and explores how these texts fit into the history of ideas and reflect the larger religious debate occurring in England in the 16th century. It also explores Turner's connection to the German reformer Urbanus Rhegius. I argue the connection between these two men and their writings function as a microcosm of the Reformation. / Master of Arts

Objetivos: Descrever a frequência, e investigar fatores preditivos, de óbito fetal espontâneo (OF), em gestações com anomalias cromossômicas. Métodos: Trata-se de estudo retrospectivo, abrangendo o período de novembro de 2004 a maio de 2012, realizado na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Foram incluídas gestações únicas com diagnóstico pré-natal de trissomia dos cromossomos 21 (T21), 18, 13 (T13/18) e monossomia do X (45X), realizado até a 26ª semana de gestação. Resultados: Foram incluídas 92 gestantes com idade materna média de 32,7 ± 8,7 anos. O diagnóstico das anomalias cromossômicas (T21 n=36, T13/T18 n=25, 45X n=31) foi realizado em idade gestacional média de 18,3 ± 3,7 semanas, por meio de biópsia de vilo corial (n=22, 24%), amniocentese (n=66, 72%) e cordocentese (n=4, 4%). Malformação major estava presente em 45 (49%); e hidropisia foi identificada em 32 (35%) fetos, sendo mais frequente no grupo 45X (n=24/31 (77%) versus T21: n=6/36 (17%) e T13/18: n=2/25 (8%), p < 0,001). Exame ecocardiográfico fetal especializado foi realizado em 60% (55/92) das gestações. Dessas, 60% (33/55) apresentaram alterações na morfologia e/ou função cardíaca, sendo o achado mais frequente a comunicação interventricular (39%). Fetos com T13/18 apresentaram incidência maior de anomalias cardíacas (60% versus 25% (T21) e 29% (45X), p= 0,01). Óbito fetal ocorreu em 55 (60%) gestações e foi mais frequente no grupo 45X (n=26/31 (84%) versus T21: n=13/36 (36%) e T13/18: n=16/25 (64%), p < 0,01). A análise multivariada stepwise demonstrou associação entre hidropisia e OF em fetos com trissomia 21 (LR= 4,29; IC95%= 1,9-8,0, p< 0,0001). Em fetos com monossomia X, a presença de alterações ecocardiográficas esteve associada com menor risco de OF (LR= 0,56; IC95% = 0,27-0,85, p= 0,005). Não foram identificados fatores preditores no grupo T13/18. Conclusão: A letalidade intrauterina de fetos com anomalias cromossômicas é elevada. A presença de hidropisia aumenta o risco de óbito fetal, em gestações com trissomia 21. Enquanto, em gestações com monossomia X, a ocorrência de alterações ecocardiográficas reduz esse risco / Objectives: To describe the frequency, and associated factors, of intrauterine fetal death (IUD), in pregnancies with chromosomal abnormality. Methods: This was a retrospective (November 2004 to May 2012) performed at de department of obstetrics, Hospital das Clínicas, São Paulo University Medical School. Inclusion criteria were: singleton pregnancies with prenatal diagnosis of trisomy 21 (T21), 18, 13 (T13/18) and X monosomy (45X), performed up to 26 weeks gestation. Results: 92 women were included in the study with a mean maternal age of 32.7 ± 8.7 years. Fetal chromosomal abnormalities (T21 n=36, T13/T18 n=25, 45X n=31) were diagnosed at a mean gestational age of 18.3 ± 3.7 weeks, by chorionic villus sampling (n=22, 24%), amniocentesis (n=66, 72%) and cordocentesis (n=4, 4%). Major fetal structural abnormality was present in 45 (49%) cases; hydrops was diagnosed in 32 (35%) fetuses, and was more common in 45X group (n=24/31 (77%) versus T21: n=6/36 (17%) and T13/18: n=2/25 (8%), p < 0.001). Specialist fetal echocardiography was performed in 55 (60%) pregnancies and showed structural and/or functional abnormalities in 33 (60%) fetuses; ventricular septal defect was the most common finding (39%). T13/18 fetuses showed a higher incidence of cardiac abnormalities (60% versus 25% (T21) and 29% (45X), p= 0.01). IUD occurred in 55 (60%) pregnancies and was more common in 45X group (n=26/31 (84%) versus T21: n=13/36 (36%) and T13/18: n=16/25 (64%), p < 0.01). Stepwise logistic regression analysis demonstrated an association between hydrops and IUD in T21 pregnancies (LR= 4.29; 95%CI= 1.9-8.0, p < 0.0001). In 45X pregnancies, cardiac abnormalities were associated with a lower risk of IUD (LR= 0.56; 95%CI = 0.27-0.85, p= 0.005). No predictors of IUD were identified in T13/18 group. Conclusion: Intrauterine death rate is high in pregnancies with a fetal chromosomal abnormality. Presence of hydrops increases the risk of this complication in trisomy 21 fetuses. Whereas the presence of a cardiac abnormality is protective in X monosomy pregnancies