Since the introduction of a new type of anti-abortion legislation in the United States which bans abortions after a fetal heartbeat can be detected, women’s options regarding abortion are being limited. How “problems” are represented or constituted in legislation shows that problems are time, place and context dependant. By using Carol Bacchi’s “What’s the problem represented to be?” approach to policy analysis, problem representations and subjectification effects in the heartbeat bills were identified. The problem representation of abortion as “lack of information” emerged as the central problem representation and the subject positions that were made available limits women’s choices regarding abortion. Fetal rights emerged as the core of the argumentation in the legislation, excluding women’s rights. How the problem of abortion is represented to be, the subjectification effects and the way rights are used and argued for in antiabortion legislation shows how they effectively limits women’s abortion choices.

Thesis (M.A. (Nursing Science)) -- University of Limpopo, 2020 / The aim of the study is to determine the knowledge and practices of midwives regarding the utilization of cardiotocography in labour units, at Hospital A and Hospital B, Waterberg District in Limpopo Province. Further, the objective of the study is to explore and describe the knowledge and practices of midwives regarding the utilization of cardiotocography in labour units and to develop strategies to enhance midwifery practices and knowledge regarding the utilization of cardiotocography in the labour units of Hospital A and Hospital B. The research question is:” What is the knowledge and practices of midwives regarding the utilization of cardiotocography in the labour units of Hospital A and Hospital B?” The Donabedian Model has been used as a theoretical framework. A qualitative exploratory, descriptive and contextual research design has been used in this study. Purposive sampling was used to sample eighteen (18) participants from Hospital A and Hospital B. Data was collected using semi-structured interviews. Tesch’s eight steps of qualitative data analysis were followed and two themes and ten sub-themes emerged. The study found that there were several challenges encountered by participants such as a shortage of material and human resources and lack of continuous training which has a negative impact on the provision of midwifery care. The study recommends that the Department of Health should appointment new skilled midwives as there is shortage of staff, to improve service delivery. It should ensure that there is a guaranteed supply and availability of equipment, such as CTG. The nursing administration should ensure that there is adequate training for midwives. This includes in-service training, workshops and a post basic advanced midwifery course.

Magister Curationis - MCur / Fetal surveillance (FS) helps midwives to predict the well-being of the fetus during labour and its relationship with uterine contractions as labour progresses. Incorrect use of surveillance apparatus and wrong interpretation of data from electronic fetal heart rate monitoring have been identified as contributing factors to delayed interventions that might have prevented the development of hypoxic-ischemic encephalopathy, which is the fifth largest cause of death of children under five globally.

Simultaneous maternal indirect blood pressure measurements, electronic fetal heart rate monitoring, and ultrasonographic biophysical profile testing were used to assess maternal-fetal homeostasis in gravid ewes during gestational days 127 to 134 (term 146), during a 72-hour fast, and during treatment with thromboxane synthetase inhibitors CGS13080 and CGS12970. Seventy-five percent of the ewes (12 of 16) developed clinical signs of ovine pregnancy-induced hypertension, including maternal hypertension and fetal depression. In three untreated hypertensive ewes, pregnancy was terminated by spontaneous premature delivery, and one maternal death occurred after an eclamptic seizure. All nine ewes treated with one of the two thromboxane synthetase inhibitors responded to therapy with decreases in blood pressure and resolution of fetal depression. These nine ewes completed gestation, and were delivered at term. These data indicate that therapy with thromboxane synthetase inhibitors in this animal model of preeclampsia results in profoundly beneficial effects and suggest that further studies of thromboxane synthetase inhibitors are warranted in preeclampsia.

Introduction: Fetal weight estimations are essential to identify and treat high-risk pregnancies. According to the Swedish association for obstetricians and gynecologists, the mean deviation of estimated weight from birth weight should be 0%, and the standard deviation 8%. Aim: To evaluate fetal weight estimations, by comparing the deviation from expected weight at the examination to at birth. Methods: Eight examiners were included from the Department of Obstetrics and Gynecology at Västerås Central Hospital. All singleton pregnancies with live births examined by these examiners from week 36+0, from January 1st to February 10th, 2022, were included, with a few exceptions. The deviations mentioned above were compared using a paired T-test. Mean and standard deviations were calculated for individual examiners. Midwives and doctors were compared using an independent T-test. Results: 86 examinations were included. There was a tendency to overestimate birth weight deviation by 1.0%, with a standard deviation of 7.8%. The differences between the deviation at the weight estimation and at birth, and between the professions, were not statistically significant. Both mean and standard deviation varied between individual examiners. Conclusions: The precision found in this study fell within what is considered acceptable according to the SFOG, and the mean did not differ statistically significantly from the recommended. Differences in fetal growth rate between examination and birth may have induced an error in the results, but the magnitude of that error cannot be determined. The study indicates differences between examiners, but a larger study is needed to draw any definite conclusions.

Introdução: Atualmente, estima-se que uma em cada mil mulheres grávidas sejam portadoras de câncer. A associação do diagnóstico de câncer ao de gestação coloca a mulher numa condição vulnerável para o desenvolvimento de transtornos psicológicos. Objetivo: Comparar e avaliar a associação entre sintomatologia de depressão, ansiedade, autoestima e vínculo materno-fetal entre gestantes com diagnóstico de câncer e gestantes sem diagnóstico de câncer. Propõe-se também a realizar a análise do discurso da vivência do período gestacional com e sem o diagnóstico de câncer. Método: Foi realizado estudo transversal com 63 gestantes com diagnóstico de câncer atendidas no Ambulatório de Tumores na Gestação de um hospital universitário terciário e 72 gestantes sem diagnóstico de câncer atendidas no Ambulatório de Pré-Natal de baixo risco do mesmo serviço. Foram utilizadas as escalas de Apego Materno-Fetal (MFAS), Hospital Anxiety and Depression (HAD), Subescala de Autoestima do Prenatal Psychosocial Profile (PPP) e entrevista semidirigida que investigou questões relacionadas à gravidez e ao adoecimento por câncer. Os testes Mann-Whitney, Kruskal-Wallis, de Dunn, qui-quadrado de Pearson e o teste exato de Fisher foram utilizados. O nível de significância adotado foi de 5%. A análise qualitativa foi realizada por meio da Técnica de Análise de Conteúdo. Resultados: Neste estudo constatou-se presença de sintomatologia depressiva em 33,3% das gestantes com câncer e em 18,1% nas gestantes sem câncer. Observou-se que as gestantes com diagnóstico de câncer quando comparadas às gestantes sem diagnóstico de câncer apresentaram menor renda per capita (p > 0,001), menor escolaridade (p=0,001), maior paridade (p < 0,001), menor trabalho remunerado (p=0,015), maior prevalência de depressão (p=0,041), ansiedade (p=0,039) e autoestima rebaixada (p < 0,001). Na análise feita por meio da combinação de diagnóstico de câncer e de depressão, evidenciou-se que a ansiedade estava associada à depressão e não com o diagnóstico de câncer. Com relação à autoestima, na combinação dos grupos evidenciou-se que o rebaixamento da autoestima estava relacionado à presença de câncer e não com a depressão. Aos resultados qualitativos foram atribuídas categorias em ambos os grupos: Descoberta da gestação, Vivência pré-natal, Relacionamento com o feto e Significado da gravidez. Em relação às entrevistas somente com as gestantes com câncer foram definidas as categorias: Como foi a descoberta da doença, Vivência do tratamento do câncer, Adaptação ao adoecimento, Crenças sobre o relacionamento com o feto, Vivência do câncer na gestação e Significado atribuído ao câncer. Conclusão: Este estudo evidenciou diferenças significativas entre presença de sintomatologia depressiva, ansiosa e baixa autoestima entre gestantes com diagnóstico de câncer quando comparadas com as sem o diagnóstico. Na análise qualitativa, constatou-se que com relação ao relacionamento com o feto foram identificadas as seguintes categorias: Conversa, Bom relacionamento, Medo, Alegria, Milagre e Não se relaciona. Com relação à Vivência do câncer na gestação foram evidenciadas as categorias: Enfoque negativo, Enfoque positivo, Dualidade e Normal. Sobre o significado da gravidez, as categorias foram: Enfoque positivo, Responsabilidade e Não sabe explicar. Em relação ao significado atribuído ao câncer, as categorias demonstradas foram: Morte/sofrimento, Cura/tratamento, Superação e Causa / Introduction: Currently, it is estimated that one in every thousand pregnant women are suffering from cancer. The association of the diagnosis of cancer with that of pregnancy puts a woman in a vulnerable condition for the development of psychological disorders. Objective: This Doctoral thesis aimed to evaluate and verify the association between symptoms of depression, anxiety, self-esteem and maternal-fetal bond among pregnant women diagnosed with cancer and pregnant women without a cancer diagnosis. It also proposed to understand the discourse of the experience of the gestational period with and without the diagnosis of cancer. Method: A cross-sectional study was performed with 63 pregnant women diagnosed with cancer, assisted at the Clinic of Tumors in Pregnancy of a tertiary university hospital and 72 pregnant women without a cancer diagnosis, assisted at the Clinic of Low-risk Prenatal care of the same service. These scales were used: MFAS for maternal-fetal bonding, Hospital Anxiety and Depression (HAD), self-esteem sub-scale of Prenatal Psychosocial Profile (PPP) and a semi-structured interview that investigated issues related to pregnancy and illness due to cancer. The Mann-Whitney, Kruskal-Wallis, Dunn, Pearson\'s chi-square and Fisher\'s exact tests were used. The level of significance was 5%. The qualitative analysis was performed by means of the Content Analysis Technique. Results: In this study, the presence of depressive symptoms was found in 33.3% of pregnant women with cancer and in 18.1% pregnant women without cancer. It was observed that the pregnant women diagnosed with cancer when compared to pregnant women without a cancer diagnosis presented lower per capita income (p > .001), lower level of schooling (p=0.001); higher number of pregnancies (p < 0.001), lower paid job (p=0.015), higher prevalence of depression (p=0.041), anxiety (p=0.039) and lowered self-esteem (p < 0.001). In the analysis made through the combination of cancer diagnosis and depression, it was shown that anxiety was associated with depression and not with the diagnosis of cancer. Regarding the self-esteem, the combination of the groups showed that the lowering of self-esteem is related to the presence of cancer and not with depression. These categories were attributed to the qualitative results in both groups: Pregnancy discovery, Prenatal experience, Relationship with the fetus and Meaning of pregnancy. With respect to the interviews only with the pregnant women with cancer, the following categories were defined: How was the discovery of the disease, Cancer treatment experience, Adaptation to the illness, Beliefs about the relationship with the fetus, Cancer experience during pregnancy and Meanings attributed to cancer. Conclusion: This study showed significant differences between the presence of depressive symptomatology, anxiety and low self-esteem among pregnant women diagnosed with cancer when compared to those without the diagnosis. In the qualitative analysis, it was found that with regard to the relationship with the fetus the following categories were identified: Chatting, Good relationship, Fear, Joy, Miracle and Not related. Regarding the Cancer experience during pregnancy, the following categories were highlighted: Negative focus, Positive focus, Duality and Normal. About the meaning of pregnancy, the categories were: Positive focus, Responsibility and Cannot explain. In relation to the meaning attributed to cancer, the categories shown were: Death/suffering, Healing/treatment, Overcoming and Cause

Introdução: Atualmente, estima-se que uma em cada mil mulheres grávidas sejam portadoras de câncer. A associação do diagnóstico de câncer ao de gestação coloca a mulher numa condição vulnerável para o desenvolvimento de transtornos psicológicos. Objetivo: Comparar e avaliar a associação entre sintomatologia de depressão, ansiedade, autoestima e vínculo materno-fetal entre gestantes com diagnóstico de câncer e gestantes sem diagnóstico de câncer. Propõe-se também a realizar a análise do discurso da vivência do período gestacional com e sem o diagnóstico de câncer. Método: Foi realizado estudo transversal com 63 gestantes com diagnóstico de câncer atendidas no Ambulatório de Tumores na Gestação de um hospital universitário terciário e 72 gestantes sem diagnóstico de câncer atendidas no Ambulatório de Pré-Natal de baixo risco do mesmo serviço. Foram utilizadas as escalas de Apego Materno-Fetal (MFAS), Hospital Anxiety and Depression (HAD), Subescala de Autoestima do Prenatal Psychosocial Profile (PPP) e entrevista semidirigida que investigou questões relacionadas à gravidez e ao adoecimento por câncer. Os testes Mann-Whitney, Kruskal-Wallis, de Dunn, qui-quadrado de Pearson e o teste exato de Fisher foram utilizados. O nível de significância adotado foi de 5%. A análise qualitativa foi realizada por meio da Técnica de Análise de Conteúdo. Resultados: Neste estudo constatou-se presença de sintomatologia depressiva em 33,3% das gestantes com câncer e em 18,1% nas gestantes sem câncer. Observou-se que as gestantes com diagnóstico de câncer quando comparadas às gestantes sem diagnóstico de câncer apresentaram menor renda per capita (p > 0,001), menor escolaridade (p=0,001), maior paridade (p < 0,001), menor trabalho remunerado (p=0,015), maior prevalência de depressão (p=0,041), ansiedade (p=0,039) e autoestima rebaixada (p < 0,001). Na análise feita por meio da combinação de diagnóstico de câncer e de depressão, evidenciou-se que a ansiedade estava associada à depressão e não com o diagnóstico de câncer. Com relação à autoestima, na combinação dos grupos evidenciou-se que o rebaixamento da autoestima estava relacionado à presença de câncer e não com a depressão. Aos resultados qualitativos foram atribuídas categorias em ambos os grupos: Descoberta da gestação, Vivência pré-natal, Relacionamento com o feto e Significado da gravidez. Em relação às entrevistas somente com as gestantes com câncer foram definidas as categorias: Como foi a descoberta da doença, Vivência do tratamento do câncer, Adaptação ao adoecimento, Crenças sobre o relacionamento com o feto, Vivência do câncer na gestação e Significado atribuído ao câncer. Conclusão: Este estudo evidenciou diferenças significativas entre presença de sintomatologia depressiva, ansiosa e baixa autoestima entre gestantes com diagnóstico de câncer quando comparadas com as sem o diagnóstico. Na análise qualitativa, constatou-se que com relação ao relacionamento com o feto foram identificadas as seguintes categorias: Conversa, Bom relacionamento, Medo, Alegria, Milagre e Não se relaciona. Com relação à Vivência do câncer na gestação foram evidenciadas as categorias: Enfoque negativo, Enfoque positivo, Dualidade e Normal. Sobre o significado da gravidez, as categorias foram: Enfoque positivo, Responsabilidade e Não sabe explicar. Em relação ao significado atribuído ao câncer, as categorias demonstradas foram: Morte/sofrimento, Cura/tratamento, Superação e Causa / Introduction: Currently, it is estimated that one in every thousand pregnant women are suffering from cancer. The association of the diagnosis of cancer with that of pregnancy puts a woman in a vulnerable condition for the development of psychological disorders. Objective: This Doctoral thesis aimed to evaluate and verify the association between symptoms of depression, anxiety, self-esteem and maternal-fetal bond among pregnant women diagnosed with cancer and pregnant women without a cancer diagnosis. It also proposed to understand the discourse of the experience of the gestational period with and without the diagnosis of cancer. Method: A cross-sectional study was performed with 63 pregnant women diagnosed with cancer, assisted at the Clinic of Tumors in Pregnancy of a tertiary university hospital and 72 pregnant women without a cancer diagnosis, assisted at the Clinic of Low-risk Prenatal care of the same service. These scales were used: MFAS for maternal-fetal bonding, Hospital Anxiety and Depression (HAD), self-esteem sub-scale of Prenatal Psychosocial Profile (PPP) and a semi-structured interview that investigated issues related to pregnancy and illness due to cancer. The Mann-Whitney, Kruskal-Wallis, Dunn, Pearson\'s chi-square and Fisher\'s exact tests were used. The level of significance was 5%. The qualitative analysis was performed by means of the Content Analysis Technique. Results: In this study, the presence of depressive symptoms was found in 33.3% of pregnant women with cancer and in 18.1% pregnant women without cancer. It was observed that the pregnant women diagnosed with cancer when compared to pregnant women without a cancer diagnosis presented lower per capita income (p > .001), lower level of schooling (p=0.001); higher number of pregnancies (p < 0.001), lower paid job (p=0.015), higher prevalence of depression (p=0.041), anxiety (p=0.039) and lowered self-esteem (p < 0.001). In the analysis made through the combination of cancer diagnosis and depression, it was shown that anxiety was associated with depression and not with the diagnosis of cancer. Regarding the self-esteem, the combination of the groups showed that the lowering of self-esteem is related to the presence of cancer and not with depression. These categories were attributed to the qualitative results in both groups: Pregnancy discovery, Prenatal experience, Relationship with the fetus and Meaning of pregnancy. With respect to the interviews only with the pregnant women with cancer, the following categories were defined: How was the discovery of the disease, Cancer treatment experience, Adaptation to the illness, Beliefs about the relationship with the fetus, Cancer experience during pregnancy and Meanings attributed to cancer. Conclusion: This study showed significant differences between the presence of depressive symptomatology, anxiety and low self-esteem among pregnant women diagnosed with cancer when compared to those without the diagnosis. In the qualitative analysis, it was found that with regard to the relationship with the fetus the following categories were identified: Chatting, Good relationship, Fear, Joy, Miracle and Not related. Regarding the Cancer experience during pregnancy, the following categories were highlighted: Negative focus, Positive focus, Duality and Normal. About the meaning of pregnancy, the categories were: Positive focus, Responsibility and Cannot explain. In relation to the meaning attributed to cancer, the categories shown were: Death/suffering, Healing/treatment, Overcoming and Cause

OBJETIVOS: Comparar resultados perinatais entre gemelares, com dopplervelocimetria da artéria umbilical (AU) com fluxo diastólico presente (FDP), discordantes (GD) e concordantes (GC) em relação ao peso estimado fetal (PEF) e de acordo com a corionicidade. MÉTODOS: Estudo retrospectivo, caso-controle, desenvolvido na Clínica Obstétrica HCFMUSP entre janeiro 2005 e dezembro 2015. Para cada GD, foram selecionados 2 controles de GC, pareados pela idade gestacional do parto (IG) e corionicidade. Critérios de inclusão: discordância PEF >= 20%, Doppler da artéria umbilical (AU) com fluxo diastólico presente, ausência de malformação ou cromossomopatias, diamniótica, fetos vivos na primeira avaliação, ausência de complicações da monocorionicidade, parto na instituição. Resultados perinatais considerados: peso no nascimento, IG no parto, internação na unidade de terapia intensiva (UTI) neonatal, tempo de internação na UTI, suporte ventilatório (VM), hemorragia periventricular (HIPV), hipoglicemia (HG), icterícia (Ic), enterocolite necrosante (EN), sepse (Sp), óbito perinatal. Foram comparados os resultados perinatais dos fetos maiores e menores entre os grupos GD e GC. O resultado perinatal do feto menore foi comparado de acordo com a presença ou ausência de restrição de crescimento fetal (RCF). RESULTADOS: Selecionados 14 GD e 28 GC monocoriônicos (MC), e 38 GD e 76 GC dicoriônicos (DC). Fetos menores MC GD apresentaram maior TI (30,60 ± 20,19 vs 10,68 ± 11,64 dias, P<0,001), maior frequência de Ic (78,6% vs 28,6%; P=0,003; RC=9,17) e Sp (21,4% vs 0%; P=0,032; RC=23,42) em comparação com fetos menores GC. Nos DC, fetos menores GD apresentaram maior frequência de Sp (10,5% vs 1,3%; P=0,042; RC=8,82), HG (15,8% vs 3,9%; P=0,003; RC=4,56), EN (5,3% vs 0%; P=0,044; RC=20,63) e Ic (57,9% vs 28,9%, P=0,003; RC=3,38) comparado com fetos menores GC. Dentre os fetos menores MC, 10 (71,4%) tem RCF e dentre os DC menores, 21 (55,3%). Os gemelares menores sem RCF apresentaram frequência de morbidade neonatal similar entre os GD e GC, exceto pelo menor peso no nascimento do feto GD DC (2167,35 vs 2339,68g, P=0,026). CONCLUSÃO: Na presença do Doppler AU com FDP, o feto menor GD apresenta maior frequência de morbidades perinatais comparado aos fetos menores GC, independentemente da corionicidade. A presença da RCF, e não apenas a discordância de peso entre os fetos, parece ser responsável pela piora dos parâmetros de morbidade neonatal dentre os fetos GD / OBJECTIVE: The aim of this study was to compare the perinatal outcome between fetal weight discordance (FwD) with fetal weight concordant (FwC) twins, with umbilical artery (UA) Doppler with positive end-diastolic flow, according to chorionicity. METHODS: This was a retrospective case-control study of twin pregnancy over an 11-year period in a tertiary referral center. For each FwD, it was selected 2 controls of FwC matched for gestational age at delivery and chorionicity. The inclusion criteria were: estimated fetal weight (EFW) discordance >= 20%, UA Doppler with positive end-diastolic flow, absence of fetal malformation or chromosomal abnormalities, known chorionicity, diamniotic pregnancies, both fetuses alive at the first assessment, absence of monochorionic (MC) complications, delivery in our institution. The perinatal outcomes considered were: birth weigh (BW), length of hospital stay (LOS), admission to the neonatal intensive care unit (NICU), length of NICU stay, need for ventilator support, intraventricular hemorrhage (IVH), hypoglycemia (Hp), jaundice (JD), necrotizing enterocolitis (NE), sepsis (SP), intrauterine and neonatal death. Perinatal outcome of the smaller and larger twin comparisons between FwD with FwC were analyzed according to chorionicity. In addition, perinatal outcome from smaller twin was compared between FwD with FwC with and without fetal growth restriction (FGR). RESULTS: A total of 14 pregnancies with FwD and 28 with FwC of MC twin and 38 pregnancies with FwD and 76 with FwC of dichorionic (DC) twin were selected. According to chorionicity, in MC FwD group, the smaller twin presented presented longer LOS (30.60 ± 20.19 vs 10.68 ± 11.64 days, P < 0.001), higher frequency of SP (21.4% vs 0%; P=0.032; OR=23.42) and JD (78.6% vs 28.6%; P=0.003; OR=9.17) compared to smaller FwC twin; whereas in DC FwD group, smaller twin presented higher frequency of SP (10.5% vs 1.3%; P=0.042; OR=8.82), Hp (15.8% vs 3.9%; P=0.003; OR=4.56), NE (5.3% vs 0%; P=0.044; RC=20.63) and JD (57.9% vs 28.9%, P=0.003; OR=3.38) compared to smaller FwC twin. FGR in the smaller MC twin was observed in 71.4% (n=10) and in the smaller DC twin, 55.3% (n=21). Twin pregnancies without FGR had similar frequency of neonatal morbidity in discordant and concordant groups, excepted for the lower BW in FwD DC twins (2167.35 vs 2339.68g, P=0.026). CONCLUSION: Regardless chorionicity, perinatal morbidity is increased in the smaller discordant twin with UA Doppler with positive end-diastolic flow, compared to concordant smaller twin. Probably the FGR is responsible to complicate the perinatal outcome of smaller discordant twin

Choi Wai-wah. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 120-138). / Abstracts in English and Chinese. / Statement --- p.i / Acknowledgements --- p.ii / Abstract --- p.iii / Abstract (Chinese Version) --- p.v / Table of Contents --- p.vii / List of Tables --- p.xii / List of Figures --- p.xiii / List of Abbreviations --- p.xv / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- "Hemoglobin ´ؤ Structures, Types and Functions" --- p.1 / Chapter 1.1.1 --- Structures of Hemoglobin --- p.1 / Chapter 1.1.2 --- Types of Hemoglobin --- p.2 / Chapter 1.1.3 --- Functions of Hemoglobin --- p.3 / Chapter 1.2 --- Human Globin Genes and Their Regulation --- p.5 / Chapter 1.2.1 --- Organization of the Human Globin Genes --- p.5 / Chapter 1.2.2 --- Regulation of Globin Gene Expression --- p.6 / Chapter 1.2.2.1 --- The Locus Control Region (LCR) --- p.6 / Chapter 1.2.2.2 --- Cis-Regulatory Elements --- p.7 / Chapter 1.2.2.2.1 --- Promoters --- p.7 / Chapter 1.2.2.2.2 --- Enhancers --- p.7 / Chapter 1.2.2.2.3 --- Silencers --- p.8 / Chapter 1.2.2.3 --- Trans-Acting Factors --- p.8 / Chapter 1.2.2.3.1 --- GATA Family --- p.9 / Chapter 1.2.2.3.2 --- Kruppel-like Factors --- p.9 / Chapter 1.2.2.3.3 --- Nuclear Factor-Erythroid (NF-E) --- p.9 / Chapter 1.2.2.4 --- Chromatin Remodelling --- p.10 / Chapter 1.2.2.5 --- Intergenic Sequences --- p.11 / Chapter 1.3 --- Mechanisms of Hemoglobin Switching --- p.12 / Chapter 1.3.1 --- Autonomous Silencing --- p.12 / Chapter 1.3.2 --- LCR and Globin Gene Interaction --- p.12 / Chapter 1.4 --- Hemoglobinopathies --- p.14 / Chapter 1.4.1 --- α -thalassemia --- p.14 / Chapter 1.4.2 --- β -thalassemia --- p.14 / Chapter 1.4.3 --- Sickle Cell Anemia --- p.16 / Chapter 1.5 --- Therapies for β-thalassemia --- p.16 / Chapter 1.5.1 --- Blood Transfusion --- p.16 / Chapter 1.5.2 --- Bone Marrow Transplantation --- p.17 / Chapter 1.5.3. --- Gene Therapy --- p.17 / Chapter 1.6 --- Gene Switch Therapy --- p.18 / Chapter "1.6,1" --- Pharmacological Induction of HbF --- p.18 / Chapter 1.6.1.1 --- Hydroxyurea --- p.19 / Chapter 1.6.1.2 --- Butyrate --- p.20 / Chapter 1.6.1.3 --- Summary --- p.21 / Chapter 1.7 --- Objectives --- p.22 / Chapter Chapter 2 --- Induction of HbF by LC978 in K562 / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- Materials --- p.26 / Chapter 2.2.1 --- Chemicals and Reagents --- p.26 / Chapter 2.2.2 --- Kits --- p.27 / Chapter 2.2.3 --- Buffers and Solutions --- p.27 / Chapter 2.2.4 --- Primers --- p.30 / Chapter 2.2.5 --- Equipment and Other Consumables --- p.30 / Chapter 2.2.6 --- Maintenance of K562 --- p.31 / Chapter 2.2.7 --- Handling and Treatment of utilities for RNA isolation --- p.31 / Chapter 2.3 --- Methods --- p.32 / Chapter 2.3.1 --- Dose-response and time-response study of LC978 in K562 by TMB assay --- p.32 / Chapter 2.3.2 --- Detection of γ -Globin Gene Expression in LC978-induced K562 by RT-PCR --- p.33 / Chapter 2.3.3 --- Fetal Hemoglobin Analysis by Human Fetal Hemoglobin (HbF) ELISA Quantitation Kit --- p.36 / Chapter 2.3.4 --- Statistical Analysis --- p.38 / Chapter 2.4 --- Results --- p.39 / Chapter 2.4.1 --- Dose-response and time-response study of LC978 in K562 by TMB assay --- p.39 / Chapter 2.4.2 --- Detection of γ -Globin Gene Expression in LC978-induced K562 by RT-PCR --- p.45 / Chapter 2.4.3 --- Fetal Hemoglobin Analysis by Human Fetal Hemoglobin (HbF) ELISA Quantitation Kit --- p.48 / Chapter 2.5 --- Discussions --- p.51 / Chapter Chapter 3 --- Signal Transduction Pathways Modulated by LC978 / Chapter 3.1 --- Introduction --- p.54 / Chapter 3.2 --- Materials --- p.57 / Chapter 3.2.1 --- Chemicals and Reagents --- p.57 / Chapter 3.2.2 --- Kits --- p.57 / Chapter 3.2.3 --- Buffers and Solutions --- p.58 / Chapter 3.2.4 --- Primers --- p.59 / Chapter 3.2.5 --- Equipment and Other Consumables --- p.60 / Chapter 3.2.6 --- Maintenance of K562 --- p.60 / Chapter 3.2.7 --- Handling and Treatment of utilities for RNA isolation --- p.60 / Chapter 3.3 --- Methods --- p.61 / Chapter 3.3.1 --- Identification of Signaling Pathways by Microarray --- p.61 / Chapter 3.3.2 --- Real-time RT-PCR --- p.65 / Chapter 3.4 --- Results --- p.67 / Chapter 3.4.1 --- Identification of Signaling Pathways by Microarray --- p.67 / Chapter 3.4.2 --- Real-time RT-PCR --- p.74 / Chapter 3.5 --- Discussions --- p.80 / Chapter Chapter 4 --- MAPK pathways and HbF induction by LC978 / Chapter 4.1 --- Introduction --- p.84 / Chapter 4.2 --- Materials --- p.87 / Chapter 4.2.1 --- Chemicals and Reagents --- p.87 / Chapter 4.2.2 --- Kits --- p.88 / Chapter 4.2.3 --- Buffers and Solutions --- p.88 / Chapter 4.2.4 --- Equipment and Other Consumables --- p.90 / Chapter 4.2.5 --- Maintenance of K562 --- p.90 / Chapter 4.3 --- Methods --- p.91 / Chapter 4.3.1 --- "Roles of three MAPKs ´ؤ ERK, JNK and p38 in LC978-mediated γ -globin gene induction in K562 using CASE´ёØ Kits" --- p.91 / Chapter 4.3.2 --- Effect of p38 inhibitor SB203580 on HbF induction --- p.94 / Chapter 4.3.3 --- Statistical Analysis --- p.97 / Chapter 4.4 --- Results --- p.98 / Chapter 4.4.1 --- "Roles of three MAPKs - ERK, JNK and p38 in LC978-mediated γ -globin gene induction in K562 using CASETM Kits" --- p.98 / Chapter 4.4.2 --- Effect of p38 inhibitor SB203580 on HbF induction --- p.106 / Chapter 4.5 --- Discussions --- p.110 / Chapter Chapter 5 --- Summary and Prospects / Appendix / References

OBJETIVOS: Comparar resultados perinatais entre gemelares, com dopplervelocimetria da artéria umbilical (AU) com fluxo diastólico presente (FDP), discordantes (GD) e concordantes (GC) em relação ao peso estimado fetal (PEF) e de acordo com a corionicidade. MÉTODOS: Estudo retrospectivo, caso-controle, desenvolvido na Clínica Obstétrica HCFMUSP entre janeiro 2005 e dezembro 2015. Para cada GD, foram selecionados 2 controles de GC, pareados pela idade gestacional do parto (IG) e corionicidade. Critérios de inclusão: discordância PEF >= 20%, Doppler da artéria umbilical (AU) com fluxo diastólico presente, ausência de malformação ou cromossomopatias, diamniótica, fetos vivos na primeira avaliação, ausência de complicações da monocorionicidade, parto na instituição. Resultados perinatais considerados: peso no nascimento, IG no parto, internação na unidade de terapia intensiva (UTI) neonatal, tempo de internação na UTI, suporte ventilatório (VM), hemorragia periventricular (HIPV), hipoglicemia (HG), icterícia (Ic), enterocolite necrosante (EN), sepse (Sp), óbito perinatal. Foram comparados os resultados perinatais dos fetos maiores e menores entre os grupos GD e GC. O resultado perinatal do feto menore foi comparado de acordo com a presença ou ausência de restrição de crescimento fetal (RCF). RESULTADOS: Selecionados 14 GD e 28 GC monocoriônicos (MC), e 38 GD e 76 GC dicoriônicos (DC). Fetos menores MC GD apresentaram maior TI (30,60 ± 20,19 vs 10,68 ± 11,64 dias, P<0,001), maior frequência de Ic (78,6% vs 28,6%; P=0,003; RC=9,17) e Sp (21,4% vs 0%; P=0,032; RC=23,42) em comparação com fetos menores GC. Nos DC, fetos menores GD apresentaram maior frequência de Sp (10,5% vs 1,3%; P=0,042; RC=8,82), HG (15,8% vs 3,9%; P=0,003; RC=4,56), EN (5,3% vs 0%; P=0,044; RC=20,63) e Ic (57,9% vs 28,9%, P=0,003; RC=3,38) comparado com fetos menores GC. Dentre os fetos menores MC, 10 (71,4%) tem RCF e dentre os DC menores, 21 (55,3%). Os gemelares menores sem RCF apresentaram frequência de morbidade neonatal similar entre os GD e GC, exceto pelo menor peso no nascimento do feto GD DC (2167,35 vs 2339,68g, P=0,026). CONCLUSÃO: Na presença do Doppler AU com FDP, o feto menor GD apresenta maior frequência de morbidades perinatais comparado aos fetos menores GC, independentemente da corionicidade. A presença da RCF, e não apenas a discordância de peso entre os fetos, parece ser responsável pela piora dos parâmetros de morbidade neonatal dentre os fetos GD / OBJECTIVE: The aim of this study was to compare the perinatal outcome between fetal weight discordance (FwD) with fetal weight concordant (FwC) twins, with umbilical artery (UA) Doppler with positive end-diastolic flow, according to chorionicity. METHODS: This was a retrospective case-control study of twin pregnancy over an 11-year period in a tertiary referral center. For each FwD, it was selected 2 controls of FwC matched for gestational age at delivery and chorionicity. The inclusion criteria were: estimated fetal weight (EFW) discordance >= 20%, UA Doppler with positive end-diastolic flow, absence of fetal malformation or chromosomal abnormalities, known chorionicity, diamniotic pregnancies, both fetuses alive at the first assessment, absence of monochorionic (MC) complications, delivery in our institution. The perinatal outcomes considered were: birth weigh (BW), length of hospital stay (LOS), admission to the neonatal intensive care unit (NICU), length of NICU stay, need for ventilator support, intraventricular hemorrhage (IVH), hypoglycemia (Hp), jaundice (JD), necrotizing enterocolitis (NE), sepsis (SP), intrauterine and neonatal death. Perinatal outcome of the smaller and larger twin comparisons between FwD with FwC were analyzed according to chorionicity. In addition, perinatal outcome from smaller twin was compared between FwD with FwC with and without fetal growth restriction (FGR). RESULTS: A total of 14 pregnancies with FwD and 28 with FwC of MC twin and 38 pregnancies with FwD and 76 with FwC of dichorionic (DC) twin were selected. According to chorionicity, in MC FwD group, the smaller twin presented presented longer LOS (30.60 ± 20.19 vs 10.68 ± 11.64 days, P < 0.001), higher frequency of SP (21.4% vs 0%; P=0.032; OR=23.42) and JD (78.6% vs 28.6%; P=0.003; OR=9.17) compared to smaller FwC twin; whereas in DC FwD group, smaller twin presented higher frequency of SP (10.5% vs 1.3%; P=0.042; OR=8.82), Hp (15.8% vs 3.9%; P=0.003; OR=4.56), NE (5.3% vs 0%; P=0.044; RC=20.63) and JD (57.9% vs 28.9%, P=0.003; OR=3.38) compared to smaller FwC twin. FGR in the smaller MC twin was observed in 71.4% (n=10) and in the smaller DC twin, 55.3% (n=21). Twin pregnancies without FGR had similar frequency of neonatal morbidity in discordant and concordant groups, excepted for the lower BW in FwD DC twins (2167.35 vs 2339.68g, P=0.026). CONCLUSION: Regardless chorionicity, perinatal morbidity is increased in the smaller discordant twin with UA Doppler with positive end-diastolic flow, compared to concordant smaller twin. Probably the FGR is responsible to complicate the perinatal outcome of smaller discordant twin