Intrauterine infection with the oral commensal anaerobe Fusobacterium nucleatum has been associated with adverse pregnancy outcomes. We have previously established a mouse model to study the mechanism of hematogenous F. nucleatum leading to fetal and neonatal death. Here, we report that Toll-like Receptor 4 (TLR4) from the maternal rather than paternal, and endothelial rather than hematopoietic cells mediate placental inflammation, especially the production of the proinflammatory cytokine interleukin-1 beta. Downstream of TLR4, a spatiotemporal pattern of the transcription factor NF-kB activation was observed spreading from the decidual endothelium to the surrounding spongiotrophoblasts within the first six hours of infection. Maternal TRIF, an adaptor protein downstream of TLR4 pathway, but not NLRP3, a cytosolic signaling receptor that constitutes inflammasome complex, mediated the fetal and neonatal death. In an effort to find a prophylactic preventive method against the detrimental birth outcome induced by F. nucleatum placental infection, omega-3 fatty acids were tested for their anti-inflammatory properties. Omega-3 oil supplementation in pregnant mice inhibited the transcription and release of inflammatory cytokines, prevented fetal and neonatal death, and also suppressed the proliferation of F. nucleatum in the placenta. Moreover, omega-3 supplementation was shown to enhance neutrophil recruitment to the site of infection. However, omega-3 supplementation did not protect the pregnancy from Listeria monocytogenes infection in vivo, despite the in vitro results where inflammation induced by both Gram-negative and Gram-positive bacteria were suppressed by omega-3 fatty acids. This study presents the first direct evidence of maternal, rather than fetal, signal leading to adverse pregnancy outcome, and suggests an exciting therapeutic potential of dietary omega-3 fatty acids.

No description available.

No description available.

No description available.

Preterm birth is a leading cause of both maternal and neonatal morbidity and mortality. It occurs in roughly one in every ten pregnancies, and at an even higher rate among Black Americans and residents of underdeveloped nations. Preterm birth can be initiated in response to a maternal or neonatal indication, or can occur spontaneously. Though indications for the former may vary, the most frequent indication for indicated preterm birth is preeclampsia, a disorder of pregnancy marked by high blood pressure and systemic organ damage. While spontaneous preterm birth and preeclampsia account for a substantial fraction of the burden of prematurity, our understanding of the triggers for and pathogenesis of both diseases are lacking. As a result, we are not able to accurately identify women early in pregnancy who are at high risk of having a spontaneous preterm birth or of developing preeclampsia. There is mounting evidence that local and systemic inflammation, infection, and environmental exposures impact the vaginal ecosystem and may be triggers of spontaneous preterm birth and preeclampsia. In this thesis, I explore the role of vaginal microbes, metabolites, and immune factors in spontaneous preterm birth and preeclampsia. After reviewing what is known about the vaginal ecosystem in spontaneous preterm birth and preeclampsia, I present a paired study of the vaginal microbiome and metabolome in a cohort of 232 women, 80 of whom delivered spontaneously preterm, and whose vaginal ecosystems were profiled during the second trimester of pregnancy. In this study I identify several metabolites strongly associated with spontaneous preterm birth, and suggest that many of these may be exogenous in origin. I also use metabolic models to investigate tyramine, a metabolite found to be associated with lower risk of spontaneous preterm birth. Finally, using predictive models I show that vaginal metabolite levels can be used to identify women at risk of spontaneous preterm birth months in advance. I then present a second study of the vaginal microbiome and immune factors in a cohort of 124 women, 62 of whom developed severe preeclampsia, and whose vaginal ecosystems were profiled at the end of the first trimester. In this study, I demonstrate for the first time that the levels of vaginal microbes early in pregnancy as well as genomic variation in the vaginal microbiome are associated with the risk of developing preeclampsia. I also identify that many vaginal immune factors are significantly depleted in the vaginal ecosystem of women who develop severe preeclampsia. I then use predictive models to show that the levels of vaginal microbes are modestly predictive of preeclampsia risk, and that features from the vaginal ecosystem can be used to improve current methods for the identification of women at risk for severe preeclampsia. Finally, I show that the microbiome signature associated with severe preeclampsia replicates in an independent cohort, suggesting that the early pregnancy vaginal microbiome is robustly associated with the diagnosis of preeclampsia months later in pregnancy. Overall, the microbial and molecular signatures that I identify in these studies contribute novel insight to our understanding of the signs and pathogenesis of both spontaneous preterm birth and preeclampsia, and in doing so, suggest novel approaches to intervention and diagnosis.

This dissertation investigates the pressing issue of education in cardiac arrest during pregnancy, an emergency of life-threatening significance that necessitates a coordinated response from maternal and neonatal healthcare teams. The study encompasses three primary chapters, each addressing a crucial facet of this intricate scenario. In the chapter titled "Cardiac Arrest in Pregnancy: A Scoping Review on Knowledge and Confidence in a Maternal & Neonatal Response," an extensive examination of existing literature illuminated substantial knowledge gaps in the resuscitation of pregnant individuals, a concern that has persisted for over a decade. These gaps encompass critical domains, including a dearth of high-quality research with a heavy reliance on limited experimental designs, small sample sizes that curtail the generalizability of findings, a lack of comprehensive comparisons among various teaching strategies for enhancing knowledge and confidence, an emphasis on short-term outcomes without adequate longitudinal assessments of knowledge retention and clinical impact, a need for tailored education programs catering to diverse healthcare professionals, and a scarcity of research on collaborative learning experiences, particularly concerning neonatology teams. These identified gaps offer valuable opportunities for future research aimed at fortifying the evidence base, refining educational approaches, and ultimately enhancing the management of cardiac arrest during pregnancy and neonatal resuscitation. This manuscript underscores the pressing need to expand educational initiatives beyond obstetrical units and to foster interdisciplinary collaboration among healthcare teams. The chapter titled, "Escaping PowerPoint: Enhancing Knowledge, Satisfaction, and Self-Confidence in Cardiac Arrest in Pregnancy," introduces an innovative teaching strategy known as the Virtual Escape Room (VER). The randomized controlled study compares the effectiveness of this virtual gamified approach with a traditional online PowerPoint method in improving knowledge acquisition, learner satisfaction, and self-confidence. The findings demonstrate the statistically significant superiority of the VER in enhancing these critical outcomes, highlighting the potential of immersive learning experiences in healthcare education. Notably, the data reveal a substantial increase in mean scores from the knowledge pre-test (M = 59.58, SD = 16.30) to the knowledge post-test (M = 68.24, SD = 17.42), t(64) = 5.635, p < .001 . The assessment tools employed included a knowledge quiz and The National League for Nursing (NLN) Student Satisfaction and Self-Confidence instruments. The chapter titled "Puzzling Out the Correlates of Learner Engagement and Exploring Motivational States within a Virtual Escape Room," delves into the intricate aspects of learner engagement within the gamified learning environment of the VER. It uncovers the relationships between engagement, learner satisfaction, and specific engagement components such as enjoyment, creative thinking, and dominance. This manuscript underscores the multifaceted nature of engagement and highlights the imperative need for further research to achieve a more profound comprehension of its role in shaping learning outcomes. The study employed the Gameful Experience Scale (GAMEX) and the Telic/Paratelic State Measure (TPSI) instrument. Notably, statistically significant positive correlations were observed, including r = 0.346 (p = 0.005) between the Enjoyment Score and knowledge post-test, r = 0.305 (p = 0.013) between the Creative Thinking Score and knowledge post-test, and r = 0.255 (p = 0.04) between the Dominance Score and knowledge post-test. Additionally, a significant interaction effect emerged between the T/PSI score (pre vs. post) and the educational intervention (VER vs. control group). T/PSI score increased from 35.83 (SD = 8.67) before the intervention to 38.86 (SD = 9.91) after the intervention, indicating a substantial change. In contrast, there was no statistically significant difference in T/PSI scores before and after the traditional PowerPoint intervention for the control group, where the mean scores changed from 35.89 (SD = 7.02) to 35.57 (SD = 7.94). These findings strongly suggest that the VER condition contributes to a paratelic state among participants when compared to the control condition. This dissertation underscores the paramount importance of effective education in managing cardiac arrest during pregnancy, given the persistent knowledge gaps among resuscitation teams. The introduction of the VER as an innovative educational strategy represents a significant advancement in addressing these deficits. Furthermore, the exploration of engagement and motivational states within the gamified learning environment offers valuable insights into the complexities of learner engagement, paving the way for more effective educational strategies in healthcare settings. Ultimately, these findings have the potential to empower healthcare teams, potentially reducing maternal mortality rates and improving neonatal outcomes in the face of this critical emergency.

No description available.

Behavioral and physiological reactivity, and its relationship to cardiovascular disease has been studied in men for a number of years, and the expression of anger has been identified as a possible contributing factor. Few studies, however, have focused specifically on the reactivity of women, and those which have suggest that women are less reactive to laboratory tasks than men. For the present study, 45 undergraduate women, ages 19-21 were selected from a larger sample of 135 women to represent three discrete groups: (1) low anger/low denial, (2) high anger/low denial, and (3) low anger/high denial, based on their scores on the State-Trait Anger Expression Inventory, P and the Marlowe-Crowne Social Desirability Scale. It was hypothesized that the three groups would show reliable differences in heart rate and blood pressure during presentation of a stressful laboratory stimulus, the Stroop Color and Word Test. Each subject received three counterbalanced conditions: (1) no feedback, (2) error feedback without observer present, (3) error feedback with observer present. As hypothesized, women who reported a high level of denial and a low level of anger exhibited reliably greater systolic blood pressure to the no-feedback condition than subjects who reported low levels of denial and anger. The hypothesis that all groups would display greater A reactivity in a condition which provided error feedback with observation was not supported. / Master of Science

The effect of comprehensive weight reduction program on selected blood parameters, body composition, and nutrient intake was investigated in 56 obese black women, 22 to 51 years old. Subjects attended nutrition and behavior modification classes once per week for 3 months. Twenty subjects participated in a low impact aerobics programs 3 times per week for 3 months. A 3.8 kg average weight loss was observed. A 2.6% significant reduction in body fat (BF) was observed in the exercise group. Total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) fell significantly from 198 to 175 mg/dL, and 130 to 109 mg/dL, respectively, in the exercise group. High density lipo-protein2-cholesterol (HDL2-C) was lowered significantly from 24 to 17 mg/dL in the non-exercise group. Triglycerides, HDL-C, TC/HDL-C ration, glucose, thyroxin, and insulin values were not significantly altered. Significant reductions in protein, fat, and cholesterol intake were reported. A comprehensive weight loss treatment promoted gradual weight loss, changes in body composition and food intake patterns, and significantly altered some blood lipid levels in obese black females. / Master of Science

The current study investigated the impact of Learned Helplessness (LH) training on normal (N), depressed (D), and bulimic (B) female college students (N=135). Participants were selected through a screening procedure using an eating behavior questionnaire and the Beck Depression Inventory (BDI; Beck, 1971) as the primary instruments. Bulimic subjects met the DSM-III criteria for that disorder, and depressed subjects met a criterion of 20 or above on the BDI. Normal subjects had BDI scores below 10 and endorsed 1 or less of the critical items regarding eating behavior which had been used to select bulimic subjects. A11 three groups were matched for weight, height, and age. Each category of subjects was divided into three groups which were exposed to Learned Helplessness (LH), Contingent Feedback (CF), or No Training Control (NTC) conditions. Dependent measures included performance on an anagram test (latency and errors), performance prediction and performance satisfaction questionnaires, and a Self-Statement Test. Results indicated no difference in anagram performance following LH training relative to CF and NTC conditions for normal and bulimic subjects, although depressed subjects demonstrated longer response latency and more errors as a function of training (LH>CF). NTC subjects did not differ significantly from the other conditions, however. Ratings of performance satisfaction differed as a function of training condition in the expected directions. Bulimic subjects demonstrated an interesting pattern of declining ratings of performance satisfaction across training trials within the CF condition. Also, bulimic subjects were found to make more errors on anagrams of nonfood words relative to food words, although this pattern was not reliably related to training condition. Self-Statement Test items did not produce the expected group x training condition effects. The present findings provide limited support for the experimental hypothesis that ineffective coping in stressful situations, mediated by cognitive self-statements, is a useful model for understanding bulimia. Methodological issues are discussed, particularly issues related to subject classification. The present study was likely confounded by the presence of depression (i.e., high BDI scores) among the bulimic subjects. Future research should systematically‘ address the relationship between bulimia and depression. / Ph. D.