Medicine and Health Sciences Commons^™

Obesity-Induced Inflammation In Human Mammary Tissue: A Potential Microenvironment Favorable To The Development Of Postmenopausal Breast Cancer Via The Wnt Signaling Pathway, Agathe A. Roubert

Masters Theses

In the United States, over one third of adult women are obese, and one in eight women will be diagnosed with breast cancer in their lifetime. Obesity has been shown to be a risk factor for postmenopausal breast cancer and is associated with increased aggressiveness and poor prognosis regardless of menopausal status. However, the mechanisms involved in the relationship between obesity and breast cancer are still not fully understood. Wnt signaling is often elevated in breast tumors (~60%) and is suspected to play a key role in cancer development. It has been shown that inflammatory cytokines, such as TNF-α, IL-1β, …

The Human Intruder Test: An Anxiety Assessment In Rhesus Macaques (Macaca Mulatta), Emily J. Peterson

Masters Theses

The human intruder test (HIT) is a noninvasive tool widely used for assessing anxiety in rhesus macaques (Macaca mulatta). This thesis explores the HIT procedure and applies it to a population of monkeys with a self-injurious behavioral pathology. Individual variation on this test can be used to assess anxiety and temperament. The first experiment of this thesis applied two different procedures of the HIT to 17 monkeys at UMass. Monkeys displayed little response to the intruder, and no significant differences were detected for the two procedures. To determine whether these responses were unique to the UMass monkeys, their …

Characterization Of The Reconstituted And Native Pseudomonas Aeruginosa Type Iii Secretion System Translocon, Kathryn R. Monopoli

Masters Theses

The Type III Secretion (T3S) system is a system utilized by many pathogenic bacteria to inject proteins into host cells during an infection. Effector proteins enter the host cell by passing through the proteinaceous T3S translocon, which forms a pore on the host cell membrane. Pseudomonas aeruginosa is an opportunistic pathogen that utilizes the T3S system, and very little is known about how the P. aeruginosa translocon forms.

The proteins PopB and PopD are believed to assemble into the P. aeruginosa translocon. A pore-forming heterocomplex of PopB and PopD has been reconstituted in model membranes, however this heterocomplex has not …

The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu

Doctoral Dissertations

Among all the cancers, the death rate of colorectal cancer is one of the highest. Evidence from both murine xenograft model and human trials have shown cancer stem cells (CSCs) are responsible for the initiation, metastasis and recurrence of multiple cancers therefore targeting colorectal CSCs would be a promising chemo-preventive/ therapeutic strategy. Polymethoxyflavones including nobiletin (NBT) and 5-demethylatednobiletin (5DN) are exclusively found in citrus peels and have been shown to have anti-cancer effects. Our previous studies in the biotransformation and tissue distribution of NBT and 5DN have shown that in order to fuller evaluate the biological impact of those two …

Economics Of Fixed-Dose Combination Drugs Approved In The United States, Jing Hao

Doctoral Dissertations

Patent is the most important form of intellectual property protection for new drugs. Patent extension and market exclusivity currently serve as major regulatory incentives to promote new drugs. Combination drug, or fixed-dose combination (FDC) are formulations that contain two or more active ingredients in a single pill. FDCs, especially combinations of singe drugs that are already in the market, are common strategy for brand-name drug companies to extent the patent and exclusivity life. The substitution of single drug products that soon have generic alternatives with newer, brand-name combinations lead to potential increases in pharmaceutical expenditures and raises concerns on economic …

Molecular Mechanisms Underlying The Muscle Response To Exercise-Induced Muscle Damage In Chronic Cigarette Smokers, Nina Moore

Doctoral Dissertations

Smoking increases risk for musculoskeletal injury and protracts healing. The underlying mechanisms have not been explored, yet dysregulated inflammatory responses may contribute. To investigate these risks, Study 1 of this dissertation monitored typical responses to muscle damaging eccentric contractions (ECC) in smokers and nonsmokers. Smokers experienced greater muscle fatigue both during and immediately after ECC and greater delayed hyperalgesia, a phenomenon known as delayed onset muscle soreness (DOMS), than did non-smokers. DOMS (driven by inflammation) peaks 48h after ECC, when there is a shift from pro- to anti-inflammatory signaling; thus I chose to investigate this time further in smokers. The …

Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli

Doctoral Dissertations

Finding and treating cancer is difficult due to limited sensitivity and specificity of current detection and treatment strategies. Many chemotherapeutic drugs are small molecules that are limited by diffusion, making it difficult to reach cancer sites requiring high doses that lead to systemic toxicity and off-target effects. Tomographic detection techniques, like PET, MRI and CT, are good at identifying macroscopic lesions in the body but are limited in their ability to detect microscopic lesions. Biomarker detection strategies are extremely sensitive and able to identify ng/ml concentrations of protein, but are poor at discriminating between healthy and disease state levels due …

Impact Of A Preschool Workplace Intervention On Classroom Teachers’ Physical Activity Levels And Quality Of Life, Ogechi O. Nwaokelemeh

Doctoral Dissertations

PURPOSE: To examine the feasibility and efficacy of a three-month, cluster-randomized workplace PA intervention on PA levels and wellbeing measures in preschool classroom teachers. METHODS: Ten preschool centers were randomized into two groups; short-bouts of structured PA (SBS-PA, n=5) or traditional unstructured PA (TRAD-PA, n=5). The SBS-PA intervention consisted of 10-minute structured, teacher-led PA routines implemented within the classroom setting, followed by 20 minutes of unstructured playtime. The TRAD-PA intervention consisted of supervised 30-minute of unstructured free playtime. Both interventions were implemented during the morning and afternoon designated gross-motor playtime for 30 min/session, five days/week for three months. Participants’ …

Impact Of Exercise During Pregnancy On Maternal Outcomes Among A High-Risk Population, Carrie Nobles

Doctoral Dissertations

Prior observational research has suggested an association between increased physical activity during pregnancy and improved maternal outcomes including a reduced risk of gestational diabetes mellitus (GDM). Despite this, randomized controlled trials of prenatal exercise are sparse and only one had been conducted in a high-risk population. Therefore, we examined the association between physical activity during pregnancy and risk of adverse pregnancy outcomes in the Behaviors Affecting Baby and You (B.A.B.Y.) Study, a randomized controlled trial of a 12-week exercise intervention among a diverse group of inactive pregnant women at high-risk for GDM. The first project examined the effect of participation …

Factors Affecting The Quality Of Services Provided To Female Survivors Of Sexual Violence In Nairobi, Kenya: Perspectives From Health Practitioners, Leso Munala

Doctoral Dissertations

This study examined the experiences of practitioners facing the challenges of providing services to female survivors of sexual violence in Kenya. Specifically, the study examined how health practitioners understand their experience in responding to the needs of sexual violence survivors, how they view these women, in what ways they are helping them to heal, and in what ways the health system fails to help these women. In-depth interviews were conducted with 28 health practitioners, from eight post-rape care facilities located in Nairobi, Kenya. The questions focused on the practitioners’ workload, challenges and rewards, the emotional impact of working with survivors, …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

Recognition And Comprehension Of Speech In Noise In School-Aged Children With Unilateral Hearing Loss, Amanda M. Griffin

Doctoral Dissertations

Sentence recognition and auditory comprehension abilities of young adults with normal hearing (NH) and school-age children with NH and unilateral hearing loss (UHL) were tested in a mixed design. In Experiment 1, subjects’ sentence recognition abilities were measured in the presence of speech spectrum noise (SSN) and two-talker child babble (TTB) in co-located and spatially-separated target and masker configurations. In all conditions, reception thresholds for sentences (RTS) improved with age from six-to 12 years. Speech spectrum noise proved to be a more effective masker than TTB in all listening conditions, suggesting subjects were able to take advantage of temporal and …

Injection Drug Users’ Perceptions Of Received Nursing Care: A Case Study, Kimberly Dion

Doctoral Dissertations

The primary aim of the exploratory case study was to explore the injection drug users’ experience with received nursing care while hospitalized on a medical unit. Data were gathered using semistructured interviews with nine injection drug users at two needle exchange services. Five men and four women were interviewed for 27–90 minutes. Travelbee’s (1971) interpersonal nursing model served as the theoretic framework for this study. Data were analyzed through the process of coding, pattern matching, and the convergence of emerging themes. For the rival case, the theme of Understanding Addiction emerged. For the comparison cases, the overarching themes of Marginalization …

Guidelines For Scheduling In Primary Care: An Empirically Driven Mathematical Programming Approach, Hyun Jung Alvarez Oh

Doctoral Dissertations

Primary care practices play a vital role in healthcare delivery since they are the first point of contact for most patients, and provide health prevention, counseling, education, diagnosis and treatment. Practices, however, face a complex appointment scheduling problem because of the variety of patient conditions, the mix of appointment types, the uncertain service times with providers and non-provider staff (nurses/medical assistants), and no-show rates which all compound into a highly variable and unpredictable flow of patients. The end result is an imbalance between provider idle time and patient waiting time. To understand the realities of the scheduling problem we analyze …

Differential Microglial Activation Following Immune Challenge In Peripubertal And Adult Outbred Mice, David J. Placzek

Masters Theses

Pubertal development is a time of growth and development in the brain, leading to high sensitivity during this period. Past research in our lab has shown that shipping female inbred and outbred mice during pubertal development alters their sensitivity to steroid hormones in adulthood, thus affecting sexual receptivity, cognition, depression-like behavior, and anxiety-like behavior. Here, we test the hypothesis that mice treated with lipopolysaccharide during pubertal development would have more active microglia, the brain's immune cells, after injection than mice treated with lipopolysaccharide in adulthood. No significant interactions were observed between treatment and age between any brain area measured, suggesting …

Associations Between Alexithymia And Executive Function In Younger And Older Adults, Gennarina Diane Santorelli

Masters Theses

The prevalence of alexithymia, a condition characterized by difficulties identifying and verbalizing one’s emotions, increases across the lifespan, with older adults reporting greater alexithymic features than young and middle-aged adults. This late-life increase in alexithymia may be the product of age-related decline in prefrontal brain circuitry implicated in emotional awareness and executive processes, notably in the anterior cingulate cortex (ACC). There is a dearth of research on the link between executive function and alexithymia in healthy adults. This study determined associations between alexithymia and executive function in healthy younger and older adults. Higher alexithymia scores were predicted to be associated …

Identifying Menstrual Symptom Patterns In Young Women Using Factor And Cluster Analysis, Felicia A. Quintana-Zinn

Masters Theses

Approximately 80% of reproductive age women experience physical or emotional symptoms prior to onset of menses. Of these women, approximately 20% experience symptoms severe enough to interfere with social functioning and life activities and meet criteria for premenstrual syndrome (PMS). More than 100 different symptoms are associated with PMS, the most common of which include breast tenderness, headache, anger, and depression. Symptom groupings tend to be stable within an individual but can vary distinctly between women. Potential differences in the etiology of symptoms suggest that PMS should not be considered a single condition in research or clinical studies, but rather …

The Effects Of Ovarian Hormones And Exercise On Gene Markers Of Cardiac Dysfunction, Anisha S. Patel

Masters Theses

Heart disease is the leading cause of death in women in the United States. Premenopausal women appear to have better cardiac function and lower risk of heart disease compared to male postmenopausal female counterparts. Ovarian hormone loss influences blood pressure homeostasis and causes systemic inflammation, which may result in chronic stress on the heart. Two key physiological changes in cardiac dysfunction are reemergence of the fetal gene pattern and myocardial remodeling. Physical activity has been linked to improved cardiac function. The purpose of this study was to investigate the effects of ovariectomy on early markers of cardiac dysfunction and fibrosis …

The Quality Of Life Among Adults With Autism Spectrum Disorder, Katharine F. Moroney

Masters Theses

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that may affect several aspects of communication, including social and pragmatic functioning. There is a paucity of research in general involving adults with ASD, especially in the United States. Moreover, the strand of research that is significantly lacking involves the quality of life among adults with ASD. While considering the increase in the prevalence of ASD, it is important to empirically investigate the Quality of Life (QoL) of adults with ASD. The World Health Organization (WHO) defines QoL as, “the individual’s perception of their position in life… ranging from the person’s physical …

Do Word-Level Characteristics Predict Spontaneous Finiteness Marking In Specific Language Impairment?, Patrick S. Wilson

Masters Theses

The correct use of morphological suffixes in obligatory contexts reflects linguistic knowledge and competence of speakers. Grammatical knowledge is acquired during a child’s period of primary language acquisition, and may be partial or incomplete due to normal linguistic variation found during acquisition, due to a child’s level of progression through typical chronological development, or due to the presence of language disorders, like specific language impairment (SLI). In the current study, we ask whether characteristics of verbs make it more or less likely that children will correctly use an inflectional morpheme. The morphemes of interest in the current study were third …

Urinary Phthalate Metabolite Concentrations And Cancer Mortality In Nhanes, 1999-2006, A B. Kaiser

Masters Theses

Four in ten people in the US will be diagnosed with cancer during their lifetime. Environmental exposures are important determinants of cancer risk, causing as many as 19% of cancers worldwide. Phthalates are a group of chemicals used to increase the flexibility of plastics and vinyl in household materials such as food packaging, plastic toys, wood finishes and adhesives. Some phthalates may act as endocrine disruptors with hypothesized links to endometriosis, breast cancer, and reproductive outcomes. However, no research yet exists on phthalate exposure and all-cancer mortality. We investigated the relationship between seven urinary phthalate metabolites among 5,205 adults in …

Pre-Pregnancy Bmi And Preterm Birth Among Hispanic Teens, Allison C. Hope

Masters Theses

Preterm birth affects 12% of infants in the United States annually and is the main contributor to infant deaths and long-term neurological disabilities in offspring. Obesity is a growing problem in the U.S., and is increasingly being considered a major risk factor for adverse health outcomes. Puerto Rican teenagers have disproportionately high rates of preterm birth and obesity when compared to non-Hispanic White teenagers. Studies evaluating risk factors for preterm birth among adolescents are sparse, have inconsistent findings, and were conducted among predominantly non-Hispanic populations. Therefore, we investigated the association between BMI and preterm birth among the 419 teenage (ages …

Examining Implementation Of The Massachusetts Act Relative To Safety Regulations For School Athletic Programs (Sessions Laws: Chapter 166 Of The Acts Of 2010): A Multiple-Case Study, Mitchell L. Doucette

Masters Theses

Background/Purpose: Reducing the incidence and negative consequences of concussion among youth athletes is a public health priority. Fifty states have adopted legislation addressing the problem of sports-related concussions among youth-athletes. In 2010, Massachusetts adopted legislation based on Washington State’s Lystedt Law, enacting state-wide requirements for high school athletic programs. This study explored how the legislation has been implemented within Massachusetts schools and school-districts and identified factors influential to local implementation.

Methods: A qualitative multiple-case study approach was utilized. US Census data concerning the household median income and population size of the school-district’s representative town(s) were used to purposively recruit cases. …

Does Change In Physical Activity Predict Mental Health Outcomes In Pre-Adolescent African American Girls?, Sarah A. Burkart

Masters Theses

Pediatric obesity is a significant clinical and public health issue for African American girls in which low physical activity (PA) is a contributor. The mother-daughter relationship (MDR) has rarely been examined in the context of improving health behaviors such as PA and mental health outcomes (MHO) within this population. PURPOSE: To examine if change in PA following a 12-week culturally-tailored mother-daughter PA intervention predicts change in MHO variables (self-esteem, depressive symptoms, body image dissatisfaction) and MDR in pre-adolescent African American girls. METHODS: Mothers (n=27; age=36.0±17.0 years; body mass index (BMI)=34.0±7.4 kg/m²) and daughters (n=27; age=9.0±1.4 years; BMI=20.3±5.7 kg/m …

Thermo-Responsive Poly(N-Isopropylacrylamide) And Its Critical Solution Temperature Type Behavior In Presence Of Hydrophilic Ionic Liquids, Purnendu K. Nayak

Masters Theses

Thermo-responsive homopolymer poly(N-isopropylacrylamide), is a widely studied and used polymer. Our recent observations on thermal behavior of aqueous solutions of this polymer requires a short overview of existing results in order to understand the formation of different phases, both stable and unstable with the addition of hydrophilic Ionic liquids (ILs) 1-Butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF₄]), 1-Butyl-3-methylimidazolium acetate ([BMIM][OAc]) and 1-Butyl-3-methylimidazolium thiocyanate ([BMIM][SCN]) to the system. PNIPAM is soluble in cold water due to its inter- and intramolecular hydrogen bonding but phase separates upon heating at T > 32 , which is its lower critical solution temperature (LCST). PNIPAM exists in an …

Live Well Springfield – A Community Transformation Movement: Evaluation Of The Live Well Springfield Website, Jesse A. Mushenko

Masters Theses

The Live Well Springfield (LWS) movement is a collaborative effort of partner organizations in Springfield, Massachusetts. The project promotes healthy living by increasing knowledge and awareness of food and physical activity. A key LWS strategy was the creation of a website to function as an information hub. In addition to local event and health information, the website features 16 narratives depicting residents practicing healthy lifestyle choices, designed to encourage community engagement. To date, there has been no evaluation of the website’s reach and effect.

A mixed methods approach, surveys and focus group discussions, was designed to collect data from people …

The Role Of The Extracellular Matrix In Mediating Muscle Soreness, Karen L. Riska

Doctoral Dissertations

The goal of this dissertation was to examine the role of the extracellular matrix (ECM) in muscle soreness. Study 1 examined how the disruption of the ECM from a minor surgery (e.g. muscle biopsy) affected muscle soreness. Study 1 showed that soreness levels increased at 24 h post-biopsy compared to baseline and resolved within 96 h. However, the level of muscle soreness at 24 h post-biopsy (20 mm) was lower than that reported for performing a strenuous and naïve exercise (40–80 mm). These results will help review boards at institutions where muscle biopsies are performed understand how a muscle biopsy …

The Effects Of Menopausal Vasomotor Symptoms And Changes In Anthropometry On Breast Cancer Etiology, Victoria Hart

Doctoral Dissertations

One of the strongest predictors of breast cancer risk is mammographic density; however, incomplete understanding of the mechanisms relating density to risk has limited its use as a marker for breast cancer susceptibility. Hormone fluctuations during the menopausal transition may influence declines in mammographic density and may also trigger the onset of menopausal vasomotor symptoms (VMS), which have been associated with lower breast cancer risk. The effects of hormone changes on density, VMS, and breast cancer risk are complicated by external factors such as changing body mass and hormone therapy use during the menopausal transition. We evaluated the association between …

A Novel Population Of Natural Killer Cells Plays A Critical Role In The Depletion Of Splenic B2 B Cells During Experimental African Trypanosomiasis, Deborah Frenkel

Doctoral Dissertations

Loss of humoral immune competence in T. brucei-infected mice is associated with the apoptotic depletion of splenic transitional, marginal zone and follicular B cells as well as a depletion of CD8⁺ T cells. This occurs rapidly after infection and impairs responses to vaccine antigens in addition to responses to newly arising VSG antigenic variants, leading to uncontrolled parasite growth and death of the infected mice. Infection-induced B2 B cell and CD8⁺ T cell loss requires the presence of a novel population of natural killer (NK) cells and is mediated by a perforin-dependent process consistent with perforin- and …

Model-Based Guidance For Human-Intensive Processes, Stefan Christov

Doctoral Dissertations

Human-intensive processes (HIPs), such as medical processes involving coordination among doctors, nurses, and other medical staff, often play a critical role in society. Despite considerable work and progress in error reduction, human errors are still a major concern for many HIPs. To address this problem of human errors in HIPs, this thesis investigates two approaches for online process guidance, i.e., for guiding process performers while a process is being executed. Both approaches rely on monitoring a process execution and base the guidance they provide on a detailed formal process model that captures the recommended ways to perform the corresponding HIP. …