Medicine and Health Sciences Commons^™

Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) is a rapidly progressing, rare and highly lethal form of breast cancer. IBC is a clinical diagnosis, requiring >1/3 involvement on the affected breast and/or skin by erythema, and disease onset of < 6 months. The clinical symptoms of IBC vary in severity and presentation, these include redness, warmth, skin thickening and bruised or pink/purple discoloration appearance and skin changes such as peau d’orange. These skin symptoms are not attributed to inflammation, rather IBC is characterized by florid lymphovascular tumor emboli clogging dermal lymphatics. This leads to “classic” symptoms of breast swelling and skin edema or discoloration. To date, unique genomic drivers which differentiate IBC from non-IBC invasive breast cancers have not been identified highlighting a role for the microenvironment. Several epidemiological studies have unveiled subtype-specific risk factors associated with IBC that are known to alter the microenvironment. Obesity is an established risk factor for all subtypes of IBC. Never-breastfeeding increases risk for developing the most aggressive, triple-negative IBC. Further, never breastfeeding is associated with later clinical stage and worse outcomes. We worked to model these overlapping risk factors to understand microenvironment changes that may lead to the lymphatic change’s indicative of IBC.

First, we investigated the association of a “classic” triad of clinical IBC signs with overall survival among patients to demonstrate the most overt clinical findings of lymphatic involvement were impacting prognosis. We evaluated a triad of IBC signs, including swollen involved breast, nipple change, and diffuse skin change, using breast medical photographs from patients enrolled on a prospective IBC registry. We reported that the …

A Serological Analysis Of Sars-Cov-2 Infection In The Obstetric Population, Sophia Rose

CMC Senior Theses

In December 2019, the surfacing and spread of a novel coronavirus, SARS-CoV-2, resulted in the global COVID-19 pandemic. As a viral antigen, SARS-CoV-2 poses a particular threat to the obstetric population due to physiological and immunological changes that women face during pregnancy. While recent studies have found that SARS-CoV-2 may have better clinical outcomes as compared to other betacoronaviruses, adverse pregnancy events such as ICU admission, preeclampsia, and/or preterm birth have been associated with COVID-19. Progress has been made in better understanding the pathophysiology of SARS-CoV-2 in pregnancy, but there is still much to be known about the interaction …

The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson

Electronic Thesis and Dissertation Repository

Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted …

The Autoimmune System: The Effect Of Physiological Stressors On Autoantibody Glycosylation And Fidelity Of Autoantibody Profiles, Rahil Kheirkhah

Graduate School of Biomedical Sciences Theses and Dissertations

The presence of thousands of autoantibodies (aABs) in the human sera is typical, and therefore it is possible to identify an aAB profile for each individual. In the first part of this thesis, we will show the cerebrospinal fluid also exhibits an extraordinarily complex immunoglobulin G aAB profile that is composed of thousands of aABs. We show that the pattern of expression of individual aABs in CSF closely mimics that in the blood, indicative of a blood-based origin for CSF aABs. In addition, using longitudinal serum samples obtained over a span of nine years, we show remarkable stability in aAB …

Relation Of Flt-1 And Endothelial Function In Women Soon After Delivery: Effect Of Physical Activity And Sedentary Behavior, Chloe W. Caudell

Senior Theses

Adverse pregnancy outcomes (APOs) are believed to be caused by poor placental formation. APOs can be characterized by elevated levels of a circulating Fms-like tyrosine kinase biomarker called Flt-1, produced by the placenta when its blood vessels are shallow or inadequately formed. Flt-1 acts directly on the maternal endothelium to impair vascular function during pregnancy and contributes to maternal features of APOs. This study aimed to evaluate the relation of Flt-1 and endothelial function in women soon after delivery. This study also aimed to evaluate the relation of Flt-1 and physical activity and sedentary behavior in women during and soon …

Assessment Of Presumed Sterility Of The Human Placenta And Maternal Bladder, Ali Alhousseini

Wayne State University Dissertations

Introduction

Preterm birth is the number one cause of neonatal morbidity and mortality. A causal link has been established between infection and preterm birth. Urinary tract infection is the number one infection in pregnancy. Evaluating the existence of a placental and maternal bladder microbiome is a major scientific and clinical milestone in perinatal medicine.

Methodology and Results

Chapter 2: This is a prospective case control study. 69 placentas were collected in a sterile fashion from six groups of women without infection: Term cesarean not in labor (n=18), term cesarean in labor (n=9), term vaginal (n=21), preterm cesarean not in labor …

The Effect Of Maternal Dietary Habits During Pregnancy On Neonate Leptin Methylation Patterns And Gestational Age, Sean Fitzpatrick

Legacy Theses & Dissertations (2009 - 2024)

The health of a newborn baby is inextricably linked to the health status of its mother and in turn the mother’s diet during pregnancy. Leptin (LEP) is an adipokine hormone involved in metabolism regulation and has been linked fetal development through the hypothalamic-pituitary-adrenal axis (HPA). Prior work suggests that gestational epigenetic alterations the LEP gene may be sensitive to adverse exposures during pregnancy, which in turn could explain variation in neonate outcomes. However, no prior work has examined this possibility explicitly. The objective of this study was to investigate the association between dietary patterns of mothers during pregnancy and their …

An Evaluation Of The Use Of A Clinical Research Data Warehouse And I2b2 Infrastructure To Facilitate Replication Of Research, Bret Gardner

Theses & Dissertations

Replication of clinical research is requisite for forming effective clinical decisions and guidelines. While rerunning a clinical trial may be unethical and prohibitively expensive, the adoption of EHRs and the infrastructure for distributed research networks provide access to clinical data for observational and retrospective studies. Herein I demonstrate a means of using these tools to validate existing results and extend the findings to novel populations. I describe the process of evaluating published risk models as well as local data and infrastructure to assess the replicability of the study. I use an example of a risk model unable to be replicated …

The Effect Of Asymmetry On Pregnancy-Related Pain In The Postpartum Period, Krista G. Meder

Graduate Theses, Dissertations, and Problem Reports

Nearly 50% of women experience back pain and other lower extremity pain during pregnancy, with many reporting lasting pain postpartum. Pregnant women experience changes to their pelvis and lower extremities that do not always return to pre-pregnancy baseline. Not much is known of the lingering effects of pregnancy related asymmetry and its relationship to pain. Therefore, the purpose of this study was to assess asymmetries of the pelvis and lower extremities to determine whether malalignment is related to areas of pain at the low back, hip, thigh, knee, leg, and foot/ankle. Methods: Seventeen postpartum women and seven nulliparous controls were …

The Effects Of Pre-Pregnancy Tobacco Use On Food Cravings And Weight Gain In Pregnancy, Lauren E. Blau

Legacy Theses & Dissertations (2009 - 2024)

Smoking cessation is associated with greater frequency of food cravings, even when controlling for body mass index. Recent studies have indicated similarities between obese women and women who smoke tobacco in mood states and food craving frequency. This is consistent with the common substrate hypothesis, which postulates that shared neural pathways mediate craving across multiple domains, and could explain why it is common for women attempting to quit smoking to gain weight. Smoking cessation prior to pregnancy is strongly encouraged due to the adverse effects of tobacco use on the developing fetus. Studies have shown that women who quit smoking …

The Effects Of Continuous Insulin Pump Therapy On Glycemic Control In Pregnant Type 1 Diabetics, Kimberly Kelsey

Senior Theses

Type 1 Diabetics have various ways of managing their diabetes that have been studied for their effectiveness. Pregnancy in the Type 1 Diabetic has been understudied. It is known that Diabetics in general have poorer pregnancy outcomes because of poor glycemic control. This coupled with the fact that the body needs 3-4 times more insulin as pregnancy comes to an end makes managing blood glucose levels challenging for diabetics (Lowdermilk, 2016, p. 689). For the Type 1 Diabetic, there are two main ways to control diabetes: multiple daily injections using at least two type of insulin and continuous subcutaneous insulin …

Assessing The Effect Of Nutritional Interventions On Body Composition Changes During Pregnancy In Moderately Malnourished Malawian Women, Megan K. Kitagawa

Master's Theses

Background: Malnutrition can affect the body composition changes that occur in healthy pregnancy, resulting in adverse effects to both the mother and infant. Supplementary foods with high quality protein may result in more favorable changes in lean mass and fat mass in pregnant malnourished women.

Objective: To retrospectively assess changes in body composition in moderately malnourished pregnant Malawian women in response to one of three nutritional interventions.

Methods: Height, weight, MUAC, and TSF were measured in pregnant women with MUAC >20.6 cm and19) were compared using ANOVA. If differences were detected, differences between groups were tested using the Tukey HSD …

Preeclampsia: The Roles Of Acute Inflammation And Intrauterine Stress, Nicholas Parchim

Dissertations & Theses (Open Access)

Preeclampsia (PE) is a severe, acute disease of pregnancy affecting approximately 8% of pregnant women after week 20 of gestation. PE is characterized by hypertension and renal damage reflected by proteinuria and has significant morbidity to both mother and fetus. Maternal symptoms range from headaches, nausea, edema, to visual changes, but once maternal symptoms present, damage to the fetus has begun. Mothers who progress untreated through the disease can also experience a condition called eclampsia characterized by seizure, coma, and, ultimately, death. PE-affected newborns experience features similar to prematurity—abnormal lung and renal development, intrauterine growth retardation (IUGR), and, possibly, fetal …

Early Life Events And Motor Development: A Longitudinal Study, Tegan Grace

Theses

Longitudinal studies are important to fully understand the processes of neurological development during gestation and how risk factors present during this time impact motor development outcomes, yet few to date have focused on this critical time period.

The purpose of this study was to identify modifiable risk factors influencing motor development during the prenatal period. Of particular interest was finding out whether these risk factors differed between the sexes.

Participants (N=2900) were from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study began in May 1989 and women were recruited between 16-20 weeks gestation (m = 18 weeks) from …

Maternal Obesity And Incidence Of Depression, Caroline A. Habjan

Honors Capstone Projects - All

Obesity is a national epidemic in the United States, which both directly and indirectly affects the social productivity of individuals, the American macro economy and individuals’ personal health and well being. Depression often interferes with an individual’s ability to work, sleep, study, eat, and enjoy life. A maternal state of both obesity and depression may cause serious adverse medical conditions in the mother’s child. Taking steps to treat depression and obesity are critical in the construct of modern medicine. This project yields results that have the potential to make treatment options better tailored, more efficient, effective and economically-sound for the …

Relationships Between A Prenatal Nutrition Education Intervention And Maternal Nutrition In Ethiopia, Divya Lakshmi Selvakumar

Walden Dissertations and Doctoral Studies

In Ethiopia, 17% of pregnant women ages 18-49 are malnourished and have low awareness of prenatal nutrition, which may relate to increasingly high rates of maternal and infant mortality. The purpose of this mixed methods research study was to determine the effects of a community-based prenatal nutrition education intervention program on maternal nutrition knowledge and attitudes in the Alaje district of Ethiopia. The theoretical framework was Sen's capability theory of poverty, in which opportunities can lead to well-being and promote economic development. Research questions focused on the relationships among 8 independent variables-age, income source, degree of program implementation, marital status, …

The Influence Of Maternal Contexts On Infant Outcomes, Secondary Analysis Of Wpcr Data 2000-2010, Mary Roseanne Butler

Theses and Dissertations

Congenital heart defects (CHD) are the most prevalent birth defect in the world and occur in approximately 6-8 of every 1,000 live births (Hoffman & Kaplan, 2002). CHD continues to be one of the leading causes of infant morbidity and mortality today. Five to ten percent of all cases of CHD can be attributed to a chromosomal abnormality, 3%-5% are linked to single gene defects, and approximately 2% are a result of known environmental factors (Clark, 2001). With only 10%-15% of the causes of CHD are understood, the remaining 85%-90% of all CHD cases, the etiologies remain unknown. The purpose …

Cervical Remodeling/Ripening At Term And Preterm Delivery: The Same Mechanism Initiated By Different Mediators And Different Effector Cells, Juan Miguel Gonzalez Velez

Wayne State University Dissertations

Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied cervical remodeling at term.

We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS)and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophage infiltration and increased serum C3adesArg and C5adesArg …

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring …

Fetal Programming And Later Obesity In A Predominantly Latino Wic Population, Eric George Walsh

Loma Linda University Electronic Theses, Dissertations & Projects

Background: In utero stressors may work to program the metabolism of the developing fetus in such a way that predisposes him/her to obesity later on. Studies have shown that breastfeeding is protective against childhood obesity and suggest that after six months the weight gain in breastfed babies slows opposed to formula fed babies who continue with rapid weight gain. This slowing of weight gain has been shown to be protective against adiposity and later life weight gain.

Purpose: This study looks to further explore these findings in a low income Latino population adding mother’s feelings about the pregnancy and the …

Assessment Of The Nutrition Knowledge And Nutrition Practices Of Crisis Pregnancy Center Clients, Sarah Harger

Honors Theses

Nutrition affects people's health. People often suffer illnesses and premature death that are largely due to poor dietary choices. Some people are aware that they are eating foods that are harmful and others eat poorly out of ignorance. Pregnancy is a time during the lifecycle when nutritional intake is of particular importance. Good choices can promote health and prevent major health problems or even death for the mother and the baby.

Many people are unaware of the benefits or consequences caused by the food they eat. Particularly low-income people may not be exposed to nutrition education. Many young people are …

A Correlative Study Of An At-Risk Population And Low Birth Weight/Infant Mortality In A Northeast Oklahoma City Community, Estacia D. Thrower

McCabe Thesis Collection

Studies show that numerous and complex variables influence pregnancy outcomes and infant mortality rates. These variables include demographic, medical, physical, environmental, behavioral, and attitudinal factors and prenatal care. Improving the health of mothers and infants is a national challenge. In 1987, more than 3.8 million infants were born in the United States. Of these, 38,408 died before their first birthday. Although the infant mortality rate is at an all-time low, the pace of progress has slowed. According to Dr. Robert Deppen of the Oklahoma State Health Department, "In 1992, Oklahoma ranked 29th in the United States for infant mortality and …

Serial Cardiovascular Adaptations During Pregnancy, Mark Vincent Hart

Dissertations and Theses

Maternal cardiovascular adaptations appear to be essential in order to supply extra circulation to both the developing fetus and maternal system during a successful pregnancy. Since inadequate cardiovascular adjustments may produce abortions or maternal morbidity, the characterization of maternal cardiovascular changes during pregnancy and the elaboration of the underlying mechanism for these changes are essential to the understanding of how the heart enlarges during pregnancy and what significance this enlargement might have. To provide needed information regarding this time course and extent of maternal cardiac enlargement and the hormonal and hemodynamic changes which may be responsible for these changes, the …