This thesis explores the relationships between self-esteem and socio-economic factors and characteristics of maternity group home program participation. Self-esteem is used sometimes as the independent variable and sometimes as the dependent variable in this study. A sample of 268 women was used representing the data available in an administrative database on women admitted to the Villa Rosa program for the period from May 1998 to February 2009, after removing cases with too much of the self-esteem measure missing. Methods of analysis included; paired samples t-tests, independent samples t-tests, analysis of variance, repeated measures analysis of variance, standard multiple regression, sequential multiple regression, and multinomial logistic regression. Attempts were made to control for the influence of the several factors. The main findings of the research included: 1) Ethnicity was not found to be significantly related to discharge self-esteem. 2) Self-esteem of residents was found to be significantly healthier at discharge from the program than at intake to the program. 3) Self-esteem was not found to be significantly different between women who participated in a post-natal semi-independent living component of the program and those who did not when controlling for control variables. When the control variable of length of time in the program was removed self-esteem was found to be significantly healthier for women who participated in the post-natal semi-independent living component of the program than those who did not. 4) A significant difference was not found between the discharge self-esteem of women who reported as living with a disability at intake, and women who did not. 5) Self-esteem at discharge was found to be healthier with an increased number of days spent at Villa Rosa. 6) Less healthy intake self-esteem was associated with plans not to breastfeed. 7) More supportive attitudes of social support network as measured at intake were shown to be linked to healthier self-esteem at discharge. 8) Experiences of abuse were not shown to be significantly related to discharge self-esteem. Both support received from the significant findings, and a lack of support from insignificant findings, were found for several self-esteem theories.

This thesis explores the relationships between self-esteem and socio-economic factors and characteristics of maternity group home program participation. Self-esteem is used sometimes as the independent variable and sometimes as the dependent variable in this study. A sample of 268 women was used representing the data available in an administrative database on women admitted to the Villa Rosa program for the period from May 1998 to February 2009, after removing cases with too much of the self-esteem measure missing. Methods of analysis included; paired samples t-tests, independent samples t-tests, analysis of variance, repeated measures analysis of variance, standard multiple regression, sequential multiple regression, and multinomial logistic regression. Attempts were made to control for the influence of the several factors. The main findings of the research included: 1) Ethnicity was not found to be significantly related to discharge self-esteem. 2) Self-esteem of residents was found to be significantly healthier at discharge from the program than at intake to the program. 3) Self-esteem was not found to be significantly different between women who participated in a post-natal semi-independent living component of the program and those who did not when controlling for control variables. When the control variable of length of time in the program was removed self-esteem was found to be significantly healthier for women who participated in the post-natal semi-independent living component of the program than those who did not. 4) A significant difference was not found between the discharge self-esteem of women who reported as living with a disability at intake, and women who did not. 5) Self-esteem at discharge was found to be healthier with an increased number of days spent at Villa Rosa. 6) Less healthy intake self-esteem was associated with plans not to breastfeed. 7) More supportive attitudes of social support network as measured at intake were shown to be linked to healthier self-esteem at discharge. 8) Experiences of abuse were not shown to be significantly related to discharge self-esteem. Both support received from the significant findings, and a lack of support from insignificant findings, were found for several self-esteem theories.

[Truncated abstract] Periodontal disease is a common and underdiagnosed disease in humans that may have adverse effects on pregnancy outcomes. The aim of this thesis was to investigate the effects of periodontal disease in pregnancy by means of two observational human studies and the development of animal models of fetal and uterine exposure to periodontopathic bacteria and lipopolysaccharide. I performed a prospective study examining the rates of preterm birth, small for gestational age neonates and neonatal inflammation in 277 women who had undergone a detailed antenatal periodontal examination and oral health questionnaire. Periodontal disease was associated with small for gestational age neonates, and increased CRP levels in umbilical cord blood, but no effect was seen on the rate of preterm birth. Maternal oral health symptoms predicted both periodontal disease and newborn biometry. In a retrospective case control study, I examined the role of periodontal disease in perinatal mortality. Participants included 53 women who had experienced a perinatal loss for which no cause could be found after thorough investigation, and 111 control women. Women who had experienced a perinatal loss were more than twice as likely as controls to have periodontal disease. The incidence of periodontal disease was even higher in women in whom the perinatal loss was due to extreme prematurity. In contrast to my prospective study, risks to the pregnancy could not be predicted by maternal oral health behaviours or oral health symptoms. In order to better understand the mechanisms regulating the associations described in the human studies, two animal models were developed; one to investigate acute exposure and the second to investigate long-term exposure to periodontal pathogens. The first study examined the effects of administration of a bolus of periodontopathic bacteria and lipopolysaccharide to the pregnant sheep. Injection of bacteria and lipopolysaccharide in the amniotic fluid of the pregnant preterm sheep caused a high rate of fetal lethality, disturbance of fetal acid base status and inflammation of the fetus and membranes. Given the circumstances of exposure to periodontopathic pathogens in human periodontal disease, a model investigating long-term exposure to periodontopathic lipopolysaccharide on pregnancy outcomes was developed. ... Overall, I have demonstrated that maternal periodontal disease is associated with adverse pregnancy outcomes including fetal growth restriction and possibly perinatal loss. Mechanisms regulating these effects are likely to be mediated by fetal adaptations to intrauterine inflammation resulting in altered fetal development, growth or survival. Randomised controlled trials that are currently in progress will provide further information on the effects of periodontal disease in human pregnancy, and the efficacy of treatment to reduce these adverse outcomes.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

O prognóstico da gestação é influenciado pelo estado nutricional materno. Sabe-se que, desde a infância, as pessoas portadoras da doença falciforme apresentam crescimento deficiente. Pouco se conhece sobre a evolução do estado nutricional materno na anemia falciforme. O objetivo foi analisar o estado nutricional de gestantes portadoras de anemia falciforme, avaliando o ganho de peso, o consumo dietético materno e os resultados adversos maternos e perinatais. Métodos: Foram avaliadas 26 gestantes portadoras de anemia falciforme SS e 23 SC, a partir do início do pré-natal especializado até o puerpério. Como grupo controle foram utilizadas 63 gestantes, sem comorbidades. O estado nutricional das gestantes foi avaliado de acordo com índice de massa corporal, pré-gestacional e ao final da gravidez, bem como analisado o ganho de peso materno. O consumo dietético foi analisado utilizando-se questionário de frequência alimentar, em cada trimestre, caracterizando-se o valor energético total e a ingestão de macronutrientes e micronutrientes. As complicações maternas e perinatais foram investigadas. O nível de significância foi 0,05 (alfa=5%). Resultados: O IMC pré-gestacional foi significativamente menor no grupo SS (mediana 20,3 kg/m2) quando comparado com os grupos SC (22,7 kg/m2, p < 0,05) e controle (23,2 kg/m2, p < 0,05). O baixo peso pré-gestacional (IMC < 18,5 kg/m2) foi significativamente mais frequente no grupo SS (15,4%) quando comparado aos grupos SC (4,4%) e controle (1,6%, p=0,009). Ao final da gestação, o grupo SS apresentou menor IMC (mediana 23,1 kg/m2) quando comparado com o grupo SC (26,1 kg/m2, p < 0,05) e controle (28,5 kg/m2, p < 0,05). O ganho ponderal na gestação foi menor no grupo SS (mediana 8,0 kg) quando comparado com o grupo SC (11,9 kg, p < 0,05) e Controle (13,7 kg, p < 0,05). Na análise do consumo dietético no 2º trimestre, constatou-se que os grupos SS e SC apresentaram menor consumo de proteínas (medianas, 73 g/d e 69 g/d) quando comparados aos controles (96 g/d, p < 0,05); e o consumo de cálcio foi menor no grupo SS comparado ao controle (mediana, 410 vs. 748 g/d, p<0,05). No 3º trimestre, houve menor consumo de proteínas pelo grupo SS quando comparado com os controles (mediana, 68 g/d vs. 93 g/d, p < 0,05); o consumo de vitamina A foi menor no grupo SS quando comparado aos controles (mediana, 447 vs. 940 mcg/d, p < 0,05); o consumo de vitamina E foi menor no grupo SS (mediana, 6 mg/d) quando comparado aos grupos SC (10 mg/d) e controle (7 mg/d, p < 0,05). As complicações maternas mais frequentes foram: crise álgica, 58% no grupo SS e 44% no SC (p=NS); infecção urinária, 31% no SS e 17% no SC (p=NS); e infecção pulmonar, 35% no SS e 9% no SC (p=NS). Houve diferença significativa no diagnóstico de sofrimento fetal: SS (36%), SC (14%) e controle (13%, p=0,032). Resultados perinatais adversos foram mais frequentes nos grupos SS e SC quando comparados aos controles. Conclusões: O estado nutricional das gestantes portadoras de doença falciforme SS caracterizou-se pela desnutrição materna, com baixo ganho ponderal na gestação. O consumo dietético de macronutrientes demonstrou ingestão inadequada de proteínas nos 2º e 3º trimestres. As complicações maternas e resultados perinatais adversos foram eventos frequentes nas gestantes portadoras de doença falciforme / The prognosis of pregnancy is influenced by the mother\'s nutritional status. It is known that, from childhood, people with sickle cell disease have deficient growth. Little is known about the evolution of maternal nutritional status in sickle cell anemia. The objective was to analyze the nutritional status of pregnant women with sickle cell anemia, assessing their weight gain, maternal dietary intake, and adverse maternal and perinatal outcomes. Methods: A total of 26 pregnant women with sickle cell anemia SS and 23 SC, from the start of pre-natal to the postpartum period. It was used as a control group 63 pregnant women without comorbidities. The nutritional status of pregnant women was evaluated according to body mass index, prepregnancy and late pregnancy and maternal weight gain. Dietary intake was assessed by food frequency questionnaire in each quarter, characterizing the total energy, macronutrients and micronutrients intake. Maternal and perinatal complications were investigated. The significance level was 0.05 (alpha=5%). Results: The pre-pregnancy BMI was significantly lower in the SS group (median 20.3 kg/m2) compared to the SC group (22.7 kg/m2, p < 0.05) and control (23.2 kg/m2, p < 0.05). The low pre-pregnancy weight (BMI < 18.5 kg/m2) was significantly more frequent in the SS group (15.4%) when compared with the SC group (4.4%) and control (1.6%, p=0.009). At the end of pregnancy, the SS group had lower BMI (median 23.1 kg/m2) compared to the SC group (26.1 kg/m2, p < 0.05) and control (28.5 kg/m2, p < 0.05). Weight gain during pregnancy was lower in the SS group (median 8.0 kg) compared with the SC group (11.9 kg, p < 0.05) and control (13.7 kg, p < 0.05). The dietary intake analysis in the 2nd quarter showed that the SS and SC groups have a lower protein intake (median, 73 g/d and 69 g/d) compared to controls (96 g/d, p < 0.05); and calcium intake is lower in the SS group compared with controls (median, 410 vs. 748 g/d, p < 0.05). In the 3rd quarter, the protein intake was lower in the SS group compared with controls (median, 68 g/d vs. 93 g/d, p < 0.05); the vitamin A intake was lower in the SS group compared to controls (median, 447 vs. 940 mcg/d, p<0.05); the consumption of vitamin E was lower in the SS group (median, 6 mg/d) groups when compared to SC (10 mg/d) and control (7 mg/d, p < 0.05). The most frequent maternal complications were: a pain crisis, 58% in the SS group and 44% in SC (p=NS); urinary tract infection in 31% of SS and 17% of SC (p=NS); and pulmonary infection, 35% in the SS and 9% in the SC group (p = NS). There were significant differences in the diagnosis of fetal distress: SS (36%), SC (14%) and control (13%, p=0.032). Adverse perinatal outcomes were more common in SS and SC groups when compared to controls. Conclusions: The nutritional status of pregnant women with sickle cell disease SS is characterized by maternal malnutrition with low weight gain during pregnancy. Dietary intake of macronutrients demonstrates inadequate protein intake in the second and third quarters. Maternal complications and adverse perinatal outcomes are frequent events in pregnant women with sickle cell disease

L'infection par le cytomégalovirus humain (HCMV) est une cause majeure de mortalité chez les patients immunodéprimés et représente la première cause d'infection congénitale. HCMV est un virus complexe qui s'est adapté au système immunitaire humain en développant de multiples mécanismes d'évasion. L'infection primaire à HCMV est associée à une réplication virale prolongée avant l'établissement de la latence. Il a été montré que cette intense réplication lors de la phase initiale de l'infection était associée à une épuisement fonctionnel des lymphocytes T CD4 spécifiques du virus. Alors que les anticorps jouent un rôle dans la limitation de la dissémination virale et la prévention de l'infection à HCMV, les réponses des lymphocytes B sont peu caractérisées. Dans le présent travail, nous avons étudié l'impact de l'infection à HCMV sur le phénotype et la fonctionnalité des sous-populations de LB du sang circulant chez une cohorte de femme enceintes avec une primo-infection par HCMV en utilisant comme contrôles des sujets sains séropositifs et séronégatifs pour HCMV ainsi que des femmes enceintes séronégatives. Nous montrons que l'infection primaire par HCMV induit une expansion significative et prolongée de deux sous-populations de LB :les LB mémoires activés (CD27+CD21low) et mémoires atypiques (CD27-CD21low), précédemment décrites lors d'infection chroniques. Les LB mémoires atypiques démontrent des signes d'épuisement fonctionnel comme en témoigne une expression élevée de récepteurs inhibant le BCR et une moindre réponse à la stimulation in vitro mesurée par la production de TNF-α. Les expansions de ces deux sous-populations sont corrélées entre elles et liées à la virémie. Ces résultats contribuent à la compréhension de la régulation des réponses des LB lors d'infections virales, en montrant que l'épuisement fonctionnel de LB, précédemment décrit lors d'infections chroniques, peut également survenir lors d'infections primaires.<p>Dans un deuxième temps, nous avons étudié l'acquisition des réponses B mémoires spécifiques de HCMV dirigées contre la principale glycoprotéine de surface, la glycoprotéine B (gB), et deux polypeptides du tégument. Lors de l'infection primaire par HCMV, la production d'anticorps neutralisant le virus, dirigés contre les glycoprotéines d'enveloppe, est retardée par rapport aux anticorps dirigés contre le tégument qui sont non neutralisant. Nous montrons que le phénotype des LB mémoires spécifiques de gB est différent de celui des LB mémoires spécifiques du tégument. La majorité des LB mémoires spécifiques de gB exprime un phénotype CD27+CD21+ alors que la majorité de ceux du tégument exprime le phénotype CD27+CD21low. Nous montrons par la suite chez des sujets sains que ces deux sous-populations de LB mémoires présentent des différences phénotypiques, au niveau de l'expression de récepteurs liés au "trafficking" cellulaire ainsi qu'au niveau de la fonctionnalité. Les LB mémoires CD21low, contrairement au LB mémoires CD21high, expriment des taux bas des récepteurs CXCR5 et CCR7, qui permettent la migration vers les centres germinatifs, mais des taux élevés de CD11c promouvant la migration vers les tissus périphériques. Après stimulation in vitro, les LB mémoires CD21low vont avoir une capacité de production d'immunoglobulines immédiate mais une réponse proliférative plus faible comparée aux LB mémoires CD21+. Nous démontrons la relevance de cette division des LB mémoires sur base de l'expression du CD21 dans un modèle de vaccination de rappel contre la toxoïde tétanique (TT). Après rappel, nous observons une expansion significative de LB mémoires spécifiques de la TT exprimant un phénotype CD27+CD21lowCXCR5lowCD11chigh. Nous proposons ainsi un nouveau mécanisme de manipulation des réponses humorales par des pathogènes qui se traduit par une limitation de l'induction de réponses B effectrices. Nos travaux permettraient également une meilleure approche des réponses B mémoires physiologiques chez l'homme en proposant une classification des LB mémoires basées sur leur fonctionnalité et leur phénotype.<p><p>Human cytomegalovirus (HCMV) infection is a major cause of mortality in immunocompromised patients and is the first cause of congenital infection worldwide. HCMV is a complex virus that has developed multiples immune evasions mechanisms during its co-evolution with mankind. Although often asymptomatic, primary HCMV infection is associated with an intense and prolonged viral replication. It has been previously shown that this intense viral replication is associated with functional exhaustion of virus-specific CD4+ T cells. Although neutralizing antibodies limits viral dissemination and play a role in the prevention of HCMV infection, B cell responses during HCMV infection have been poorly studied so far.<p>In this work, we have studied the impact of HCMV infection on the phenotype and functionality of peripheral-blood B cell subsets in a cohort of pregnant women with a primary HCMV infection. Controls were healthy seronegative and seropositive HCMV donors and HCMV seronegative pregnant women. We show that primary HCMV infection induces a significant and prolonged expansion of two B-cell subsets, previously described in chronic infections :activated memory B cells (MBC) (CD27+CD21low) and atypical MBC (CD27-CD21low). Atypical MBC display signs of functional exhaustion with increased expression of inhibitory receptors and a lower response to in vitro stimulation as assessed by TNF-α production. Expansion of these two subsets are correlated and higher in subjects with detectable viremia. These results contribute to the understanding of the regulation of B cell responses during viral infections and indicate that B cell exhaustion, previously described during chronic infections, can be observed in primary infection.<p>Next, we have characterized the acquisition of HCMV-specific B cell responses directed against envelope glycoprotein B (gB) and two tegument polypeptides (pp150 and pp52). During primary HCMV infection, the production of neutralizing antibodies targeting envelope glycoproteins is delayed when compared to non-neutralizing anti-tegument antibodies. We show that gB and tegument-specific MBC have distinct phenotype during primary HCMV infection. The majority of gB-specific MBC have a CD27+CD21+ phenotype while the majority of tegument-specific MBC have a CD27+CD21low phenotype. We show that CD27+CD21+ and CD27+CD21low MBC express different pattern of chemokine receptors pattern but also have distinct functionality. CD27+CD21low MBC, on the contrary to CD27+CD21+ MBC, express low levels of CXCR5 and CCR7 that favor migration to lymph nodes and germinal centers but express high levels of CD11c that promotes migration to inflammatory tissues.<p>In vitro stimulation of sorted subsets of healthy individuals indicates that CD27+CD21low MBC have higher capacity of immediate immunoglobulin production but a lower proliferative potential as compared to CD27+CD21+ MBC. We further show the relevance of a division of MBC subsets based on CD21 expression in a model of TT booster immunization. Following booster immunization, a significant expansion of TT-specific MBC expressing the phenotype CD27+CD21lowCXCR5lowCD11chigh is observed. <p>We propose that HCMV manipulates the host humoral response by limiting the induction of gB-specific CD27+CD21low "effector" MBC. Our work also indicates that human MBC physiological responses should be studied according to their respective phenotype and functions.<p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

In this work, we found that proliferation-related prognostic gene signatures could aid treatment decision-making independent of age. This is clinically relevant for the younger breast cancer population given the potential long-term side effects of adjuvant systemic chemotherapy and hence the need to identify patients who are less likely to benefit adjuvant chemotherapy. In addition, it was clear that young age at diagnosis adds extra biological complexity, which is independent of differences in breast cancer subtype distribution. This includes enrichment with known breast cancer targets like RANKL. Whilst these results require further validation, either experimentally or in other clinical data sets, it suggests that separate therapeutic approaches may need to be specifically designed in order to improve outcomes for breast cancer arising in young women. In this regard, and based on our results and supportive evidence from other studies, we initiated a proof-of-concept prospective phase II neoadjuvant study investigating the role of denosumab, a RANKL inhibitor on modulating tumor biology in young premenopausal breast cancer patients. <p>We found that diagnosis during pregnancy does not significantly influence the classic pathological features or the prevalence of breast cancer subtypes. We also did not find obvious differences in the distribution of PIK3CA mutations. However, we found that tumors diagnosed during pregnancy have activated serotonin receptor signaling and high expression of potential breast cancer targets; of particular interest IGF1, and PDL1. Such differences appeared to be reflected in the normal pregnant breast underscoring the potential role of the pregnant breast microenvironment on the tumor transcriptome. We were not able to associate these genes with prognosis, which could be partly due to lack of statistical power. Of note, we cannot confirm whether any of these aberrations are key drivers of the biology of tumors diagnosed during pregnancy. Nevertheless, this remains the first study to look into the biology of this relatively rare disease and hence we believe it would serve as a very valuable resource for future research in this field. We are planning to perform targeted gene sequencing to further refine our understanding of the potential effect of pregnancy on the biology of these tumors. <p>In the last part of this work addressing the safety of pregnancy following breast cancer diagnosis, we identified that available studies suffered major limitations related to study design including selection bias and lack of information on patients with history of an ER-positive disease. This has resulted in advising against pregnancy in women with prior history of breast cancer. Our subsequent study has robustly addressed most of the limitations in older studies and clearly showed that pregnancy following breast cancer is safe even in women with a history of ER-positive disease. Hence, this study would provide a very important resource for the oncology community, which would aid adequate fertility counseling for young breast cancer survivors. This work is currently serving as the basis for a new prospective study by the IBCSG to test the safety of early interruption of tamoxifen in young women with early breast cancer seeking subsequent pregnancy. <p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

MA (Psychology) / Department of Psychology / See the attached abstract below

MCur / Department of Advanced Nursing Sciences / MAAS / Centre for African Studies / See the attached abstract below