Medicine and Health Sciences Commons^™

Effects Of Dietary Phytoestrogens On Spermatogenesis And Male Reproductive Tract In Mice, Trenton A. Dalm

Masters Theses

Increases in infertility over the past 50 years are linked to environmental exposures to endocrine disrupting chemicals (EDCs). One type of EDC is phytoestrogens, commonly found in soy-based diets and foods such as cauliflower, tofu, and broccoli. Phytoestrogens may bind estrogen receptors and have positive or negative effects on receptor signaling. The developing male reproductive tract is potentially susceptible to endocrine disruptors leading to changes in adult reproductive function and possibly infertility. We hypothesized that dietary phytoestrogen exposure would have a dose dependent effect with the high diet yielding the lowest sperm count and worst performance compared to the medium …

A Machine Learning Approach For Predicting Clinical Trial Patient Enrollment In Drug Development Portfolio Demand Planning, Ahmed Shoieb

Masters Theses

One of the biggest challenges the clinical research industry currently faces is the accurate forecasting of patient enrollment (namely if and when a clinical trial will achieve full enrollment), as the stochastic behavior of enrollment can significantly contribute to delays in the development of new drugs, increases in duration and costs of clinical trials, and the over- or under- estimation of clinical supply. This study proposes a Machine Learning model using a Fully Convolutional Network (FCN) that is trained on a dataset of 100,000 patient enrollment data points including patient age, patient gender, patient disease, investigational product, study phase, blinded …

Social Dominance Alters Stress-Induced Neural Activity And Generates Individual Differences In Stress Vulnerability, Jenna Lee Laymon

Masters Theses

Identifying the physiological and behavioral mechanisms that underlie stress vulnerability is a crucial step toward identifying novel targets for the prevention and treatment of stress-related disorders. Social status is a key environmental factor that contributes to individual variations in stress vulnerability. In particular, achieving a subordinate social status has been shown to produce susceptibility to anxiety-like and depressive-like behavior. In this project, our aim was to identify neural ensembles regulating how dominance status modulated stress-induced changes in avoidant behavior in male and female Syrian hamsters. Using a viral vector that codes for robust activity marker (RAM), we investigated whether stress-induced …

Development Of A Low-Dose Radiation Therapy Device For Acute Respritory Distress Syndrome, Thomas Heath Davis

Masters Theses

This research focuses on the development of a low dose radiotherapy (LD-RT) device for treatment of acute respiratory distress syndrome (ARDS), a respiratory illness that affects millions of people a year. The use of orthovoltage (200 – 500 keV) X-ray energy provides many advantages over traditional radiotherapy delivery with linear accelerators, such as low cost and greater accessibility. In addition, X-ray tubes have been shown throughout history to provide good treatment outcomes for pneumonia, and research has shown LD-RT to be just as effective with ARDS. This proposal summarizes my efforts in determining the dosimetric properties of a LD-RT system …

Blood Flow Restriction And Various Intensity Exercise In The Upper Extremity, Noelle Ashlyn Kaminski, Andrew Lowe

Masters Theses

Purpose: To determine if using Blood Flow Restriction (BFR) combined with low-load exercise can elicit an increase in strength and tendon size of the distal biceps tendon when compared to high-load exercise protocol. Methods: Twenty-one participants (11 M, 10 F; 2 Left-handed: 19 Right-handed; Age range 18-25yoa) were randomized to either the treatment group (BFR + low load exercise) or the control group (high load exercise). Participants were enrolled in a 7-week exercise protocol, with exercise sessions held twice weekly. The first week included measurements of each participant's 1 repetition maximum (1RM) and ultrasound measurements of the dominant distal bicep’s …

Does Epa Cause A Decrease In Inflammation Of Bend.3 Cells Through Ffar4?, Clay J. Weidenhamer

Masters Theses

Atherosclerosis is an inflammatory disease initiated by low and oscillatory shear stress on the endothelium. The inflammatory process recruits leukocytes to the vessel wall by expression of the adhesion molecule VCAM-1. Activation of the NF-κB inflammatory signaling pathway is responsible for the increase in VCM-1 expression. Omega 3 FAs, such as EPA, reduce the risk of atherosclerosis by decreasing this inflammatory response. The pathway by which omega 3 FAs is proposed to inhibit inflammation includes activating FFAR4 to decrease NF-κB activation thereby reducing expression of adhesion molecules. We hypothesized that treatment of endothelial cells with 30 μM EPA would decrease …

From The Dinner Pot To Smoking Pot; How A Better Understanding Of Cannabidiol In Crayfish Could Alleviate Anxiety And Modulate Hunger, Christopher Michael Timmer

Masters Theses

Anxiety affects approximately 1/3 of the US population and presents in many different forms, ranging from social to panic disorders. It also presents with high comorbidity for other mental disorders. One treatment is Selective Serotonin Reuptake Inhibitors (SSRIs) which allow for increased activation of serotonin (5-HT) receptors. SSRIs come with an extensive list of side effects, which can fail to maintain quality of life. Cannabidiol (CBD) is a cannabis derived compound which has been shown to decrease anxiety by activation of multiple subtype 5-HT amine receptors. CBD has few side effects, is not psychoactive, and exhibits anti-psychotic properties. The current …

Microbial Experience Influences Tumor- Infiltrating T Lymphocytes, Hanna Groeber

Masters Theses

Immune cells, including T cells, have been used for anti-cancer therapy with varying degrees of success. One potential reason for immunotherapy failures in clinical trials may be that typical specific pathogen free (SPF) mice do not accurately replicate human microbial experience, which has important influence on shaping the adaptive immune response. Recently, several previous studies have shown that the immune system of SPF mice more closely resembles newborn human immunity, whereas immune systems from mice exposed to diverse pathogens more closely reflect adult human immunity.

To study the impact of microbial experience on the immune response, we have adopted a …

The Determination Of Phosphorylation Of Nato3 By Pka, Miranda M. Regenold

Masters Theses

One of the leading regulators of neuronal cell differentiation in the CNS is the family of basic helix–loop–helix (bHLH) transcription factors. One of these proteins, Nato3, is associated with the formation of dopaminergic neurons. Transcription factors can be regulated by kinase activity, and in order to detect the associated change of phosphorylation of Nato3, we have generated Nato3 with specific epitope tags that allow for the detection and isolation of the Nato3 protein. Through subcloning techniques and a successful transformation of the Nato3 gene with the sequences of the 3X-Flag epitope and the Myc epitope into the pcDNA3.0 vector, we …

The Application Of Machine Learning Models In The Concussion Diagnosis Process, Sujit Subhash

Masters Theses

“Concussions represent a growing health concern and are challenging to diagnose and manage. Roughly four million concussions are diagnosed every year in the United States. Although research into the application of advanced metrics such as neuroimages and blood biomarkers has shown promise, they are yet to be implemented at a clinical level due to cost and reliability concerns. Therefore, concussion diagnosis is still reliant on clinical evaluations of symptoms, balance, and neurocognitive status and function. The lack of a universal threshold on these assessments makes the diagnosis process entirely reliant on a physician’s interpretation of these assessment scores. This study …

Is Tpmt Testing A Predictor Of Duration Of Use Or Long-Term Benefit Of Thiopurine Agents?, Shatoya R. Wilson

Masters Theses

Background: Inflammatory Bowel Disease (IBD) affects as many as 1.3 million Americans and includes both ulcerative colitis (UC) and Crohn’s disease (CD). Recent practices have moved towards using immunomodulators early in the course of disease to prevent disease progression. Patients have shown improved outcomes on immunomodulators compared to aminosalicylates, and reduced risk for tachyphylaxis compared to corticosteroid treatment. Thiopurine agents such as azathioprine and 6-mercaptopurine are immunomodulators often used to treat IBD. Unfortunately, many patients experience cytotoxicity from thiopurine use. Recent studies have shown that patients deficient in thiopurine-S-methyltransferase (TMPT), produce an overabundance of the therapeutic end product, 6-thioguanine nucleotide …

Effects Of Eicosapentaenoic Acid (Epa) On Mouse Endothelial Cell Health, Spencer C. Pageau

Masters Theses

Cardiovascular disease is the number one killer of adults in the US (~800,000 lives every year:1 in 3 deaths). Evidence suggests omega-3 fatty acids like eicosapentaenoic acid (EPA), found in fish oils, reduce the risk of developing cardiovascular diseases. Many of these diseases are caused by atherosclerotic plaque development in vessels due to endothelial cell damage initiating inflammatory responses. Recent work argues omega-3 fatty acids stimulate anti-inflammatory responses by binding to Free Fatty Acid (FFA) receptors. Inflammatory responses in endothelial cells alter the expression of many proteins that affect the function of those cells. In particular, gap junction protein (connexin: …

Impact Of Bodyweight On Tissue-Specific Folate Status, Genome Wide And Gene-Specific Dna Methylation In Normal Breast Tissues From Premenopausal Women, Armina-Lyn Frederick

Masters Theses

Obesity has reached an epidemic level in the United States. A number of epidemiological studies have established obesity as a critical risk factor for postmenopausal breast cancer (post-BC), whereas a reverse association holds prior to menopause. A significant scientific gap exists in understanding the mechanism(s) underpinning this epidemiological phenomenon, particularly the reverse association between obesity and premenopausal breast cancer (pre-BC). This study aimed to understand how folate metabolism and DNA methylation informs the association between obesity and pre-BC. Fifty normal breast tissue samples were collected from premenopausal women who underwent reduction mammoplasty. We developed and measured the breast tissue folate …

The Role Of Affective Forecasting And The Impact Bias In Nutritional Health Behaviors, Matthew D. Fallon

Masters Theses

Previous literature on affective forecasting has studied its role in health decisions, but there is little research investigating affective forecasting in diet choices and eating behaviors. The present study collected affective forecasts from 43 college participants before eating an indulgent snack and then observed emotions immediately after eating the snack. We predicted that emotion predictions would be significantly stronger than observed emotions, in support of previous literature on the impact bias. We also predicted that optimism would predict a stronger impact bias and that extraversion and neuroticism would have a role in forecasts and observed emotions. Contrary to our hypothesis, …

Effects Of Aging And Dietary Phytoestrogens On Sperm Production In Sprague Dawley Rats, Brian Cutler

Masters Theses

Estrogens, in addition to testosterone, are physiologically relevant to normal sperm production in the testis and sperm maturation in the epididymis. Previous studies from our lab demonstrated that daily sperm production declines from 15 to 18 months of age in Sprague Dawley rats, and treatment with estrogen during this period attenuated the age-associated decline. Phytoestrogens are present in standard rodent diets at high levels (350-650 mg/kg) and may be potential endocrine disruptors. The purpose of this study was to investigate the effect of removing dietary phytoestrogens during aging on sperm production. Retired breeder Sprague Dawley rats were obtained at 9 …

The Oncolytic Potential Of Tanapoxvirus To Treat Retinoblastoma, John D. Christie

Masters Theses

Retinoblastoma is the leading cause of intraocular malignancy in children under 2 years of age. Current treatments, while generally effective in eliminating the tumor, have many negative side effects. Oncolytic virotherapy is the use of either wild type or recombinant viruses, to destroy tumor cells. There are currently several viruses being engineered as potential therapeutics for a wide range of cancers. They offer tumor specific alternative to current therapies with lesser toxicity. This study looked at the oncolytic efficacy of multiple tanapoxviruses (TPV) recombinants in an in vitro retinoblastoma. Here we have tested recombinants of TPV for their ability to …

Evaluating A Novel Photochemical Tool For Labeling And Tracking Live, Endogenous Calcium-Permeable Ampars, Rosamund Elizabeth Combs-Bachmann

Masters Theses

The purpose of this research is to advance development of a photochemical tool designed to probe the role of ionotropic glutamate receptor signaling in neurodegenerative processes, and to delve more deeply into the biological processes underlying the role of these receptors in signaling and memory formation. This ligand-targeted nanoprobe was designed and developed in our lab to label endogenous calcium-permeable AMPARs (CP-AMPARs) in live cells with minimal disruption to native receptor activity. Nanoprobe is designed to use naphthyl acetyl spermine (NASPM) as a photocleavable ligand to target and covalently label native CP-AMPARs with a non-perturbing, fluorescent marker that then allows …

An Initial Analysis Of A Long-Term Ketogenic Diet’S Impact On Motor Behavior, Brain Purine Systems, And Nigral Dopamine Neurons In A New Genetic Rodent Model Of Parkinson’S Disease, Jacob Rubin, William H. Church

Masters Theses

A growing body of research suggests that dopaminergic cell death seen in Parkinson’s disease is caused by mitochondrial dysfunction. Oxidative stress, with subsequent generation of reactive oxygen species, is the hallmark biochemical product of mitochondrial dysfunction. The ketogenic diet has been found to enhance mitochondrial energy production, protect against reactive oxygen species-generated cell death, and increase adenosine, a purine that modulates dopamine activity. The current study evaluates the effects of a long-term (5-month) ketogenic diet on behavioral, neurochemical, and neuroanatomical measures in PINK1-KO rats, a new animal model of Parkinson’s disease. Both wild-type and PINK1-KO animals fed a ketogenic diet …

The Neurochemistry Of Group Singing: Bonding And Oxytocin, Jason Keeler

Masters Theses

The purpose of this study was to examine the neurochemical correlates of group vocal improvisation and to determine the feasibility of the research methods. One group of four participants sang together in two conditions: pre-composed and improvised. Concentrations of plasma oxytocin and adrenocorticotropic hormone (ACTH) were measured before and after each singing condition to assess levels of hormones associated with social affiliation, engagement and arousal. Successful implementation of the methodology, including recruitment, data collection, and sample analysis, served as the primary outcome of this study. ACTH concentrations decreased in both conditions, and significantly so in the pre-composed singing condition. Mean …

Effects Of Varus Knee Alignment And Using Toe-Cages On Frontal Plane Knee Biomechanics In Stationary Cycling, Guangping Shen

Masters Theses

Effects of varus knee alignment on the internal knee abduction moment (KAM) in walking has been widely studied. KAM has been shown to be closely associated with the development of medial knee osteoarthritis (OA). Despite the importance of the knee alignment, no studies have explored its effects on knee frontal plane biomechanics during stationary cycling. The purpose of this study was to examine the effects of varus knee alignment and using a toe-cage on the knee frontal plane biomechanics during stationary cycling. Eleven participants in each of the varus and neutral groups participated in the study. The participants performed in …

Optical Tracking System To Monitor Laparoscopic Training, William D. Rytlewski

Masters Theses

Laparoscopic Surgery, also known as Minimally Invasive Surgery, is a surgical technique where surgeons perform surgery through small incisions in the patient’s abdomen using a camera to monitor the movements of the instruments inside the patient. In order for the surgery to be performed, the surgeon must possess a unique set of skills obtained through training using a variety of techniques. Simulators are the preferred method of training for laparoscopic surgery since they provide medical residents with real world scenarios as well as a tremendous amount of feedback on what he/she did wrong or right. However, due to the high …

Biodegradable Nano-Hybrid Polymer Composite Networks For Regulating Cellular Behavior, Charles Henley Sprague

Masters Theses

Photo-crosslinkable polymeric biomaterials have emerged in the field of biomedical research to promote tissue regeneration. For example, scaffolds that can be crosslinked and hardened in situ have been known to make suitable implant alternatives. Since injectable and photo-crosslinkable biomaterials offer the advantage of being minimally invasive, they have emerged to compete with autografts, a current highly invasive method to repair diseased tissue. A series of novel photo-crosslinkable, injectable, and biodegradable nano-hybrid polymers consisting of poly(ε-caprolactone fumarate) (PCLF) and polyhedral oligomeric silsesquioxane (POSS) has been synthesized in our laboratory via polycondensation. To engineer the material properties of the nano-hybrid networks, varied …

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 …

Effects Of Fatty Acid Structure On Endothelial Cell Expression Of Connexin43, Albert E. Sowers Iii

Masters Theses

The epidemic of obesity-related metabolic and cardiovascular diseases is linked to elevated fatty acids (FA). Epidemiological data argue that trans FA contribute to the development and progression of these disease processes. Previous work suggests the similarity in structure between saturated and trans FA may stimulate inflammation through trans FA interactions with toll-like receptor 4 (TLR4). To evaluate the impact of trans FA on cardiovascular health, the response of endothelial cells to trans FA was evaluated. Specifically, responses to the 18-carbon trans FA elaidic acid (EA) were compared to the same length cis FA oleic acid (OA). Endothelial cells were exposed …

The Nutrient Intake Of Homeless Women Of Grand Rapids, Michigan, Emily D. Popma-Metsaars

Masters Theses

Background Homeless individuals comprise about 1% of the American population with 1/3 of this particular population being women. And despite the potential for hunger, the homeless population has a similar prevalence of overweight/obese as other Americans. The Heartside neighborhood of Grand Rapids is a very low-income area of the city, inhabited by the poor and homeless. The Food Access in Michigan Project is studying the relationship between food insecurity and food environments in Michigan.

Objectives The purpose of this study was to determine the characteristics of the diet of homeless women in Heartside. This study examined the level of food …

Comparison Of Dual- And Tri-Axial Accelerometer Accuracy, Lindsay Powell Toth

Masters Theses

The purpose of this study was to investigate the accuracy of the Omron HJ-720ITC and the Fitbit Zip activity monitors with regard to step count, energy expenditure, and distance traveled measurements. The importance of this research rests in the success rates of pedometer-based physical activity interventions which have been shown to increase physical activity while also enabling weight loss and lowering blood pressure in the adult population. Activity monitors available for retail sale must be found accurate for proper participation in exercise interventions especially low-cost devices as used in this study.

In order to test the accuracy of the Omron …

Effects Of Various Partial Body Cooling Techniques On Core Temperature During Recovery From Prolonged Cycling-Induced Heat Stress, Afton Danielle Seeley

Masters Theses

The purpose of this study was to investigate the effects of using an ice-vest and a palm cooling device on core and skin temperatures, heart rate, and perceived thermal comfort during a one hour recovery period following exercise in the heat. Ten recreationally active adults cycled for one hour at 50% V0₂ peak on a cycle ergometer while exposed to 36°C 45%relative humidity environmental conditions. Following exercise, each subjectwas exposed to an ice vest, a palm cooling device, or a non cooling control while seated in the environmental chamber for 60 more minutes. No significant differencewas found betweenany of …

Joint Reaction Force And Contributions Of Surrounding Muscles To Knee Joint Load During Stair Ascent In Total Knee Replacement Patients And Healthy Individuals, Robert Jacob Rasnick

Masters Theses

Total knee replacement (TKR) is commonly used to correct end stage knee osteoarthritis (OA) of the knee joint. Unfortunately, difficulty with stair climbing has been seen to exist, prolonging the challenges of TKR patents. Complete understanding of loading at the knee is of great interest in order to aid patient populations, implant manufacturers, rehabilitation, and future research. The outcome of a TKR is intended to reestablish normal motion and loading of the knee. Musculoskeletal modeling provides a means to accurately approximate joint loading and the corresponding muscle contributions during a movement.

The purpose of the present study was to examine …

Expression Of The Chemokine Receptor, Cxcr4, And Its Ligand, Sdf-1, Are Increased In Purkinje Cells Of The Multiple System Atrophy Cerebellum, Megan Welter

Masters Theses

Multiple System Atrophy (MSA) is a sporadic, neurodegenerative disease that consists of three conditions: autonomic dysfunction, Parkinsonism and cerebellar ataxia. Our lab conducted an Affymetrix global gene expression analysis using pons tissue of MSA patients to determine genes that are differentially expressed when compared to non- MSA controls. This study identified upregulated genes, including the C-X-C chemokine receptor type 4, CXCR4, to which stromal cell-derived factor-I (SDF-1) is the natural ligand. The CXCR4/SDF-1 signaling pair has been sho.wn to play multiple roles in the brain, such as inducing neuronal apoptosis and promoting leukocyte recruitment during inflammation. The MSA cerebellum presents …

Study Of The Insulin Mimetic Sodium Orthovanadate In Glucosamine Induced Insulin Resistnace In Primary Rat Hepatocytes, Kalan Mcpherson

Masters Theses

Insulin resistance and type II diabetes is a disease state characterized by a lack of sensitivity of insulin to provoke a proper response in insulin sensitive tissues. Currently, we utilize glucosamine to increase flux through the Hexosamine Biosynthetic Pathway (HBP) to induce an insulin resistance like state in primary rat hepatocytes. We tested the effectiveness of the insulin mimetic sodium orthovanadate to determine if it could elicit an insulin-like response under these conditions. Mixed results were obtained on the effectiveness of vanadate as an insulin mimetic in this insulin resistant model.