Medicine and Health Sciences Commons^™

Therapy-Induced Senescence In Cancer: Developing Senolytic-Based Combination Strategies To Delay Re-Emergence Of Triple-Negative Breast Cancer, Eesha Chakraborty

Theses and Dissertations

Therapy-induce senescence (TIS) represents a major biological outcome of many anticancer treatments and is increasingly recognized as a strategic vulnerability in triple negative breast cancer, which is a highly aggressive subtype with limited therapeutic options and frequent relapse. Here, we probed TIS as a primary cellular response that may ultimately compromise long-term outcomes using standard chemotherapeutic agents in TNBC as well as the antibody-drug conjugate sacituzumab govitecan (SG). Both chemotherapy and SG reliably induced pronounced senescence across TNBC models, yielding durable growth arrest, however, also generating a persistent reservoir of viable tumor cells capable of eventual proliferative recovery, a hallmark …

Effectiveness Of Immersive Virtual Reality Combined With Task-Specific Training On Hemiplegic Arm Function Following Stroke: A Single Case Series Study, Rahsaan J. Holley

Theses and Dissertations

Motor recovery of the arm following a neurological injury is a common goal of the rehabilitation process for individuals impacted by the condition . Due to the long-term functional implications of impaired arm movement, individuals are often trained to use compensatory strategies to complete functional tasks without incorporating the weakened limb. While compensatory strategies offer stroke survivors the opportunity to regain a level of independence, such approaches fail to directly address the underlying causes of the disability (i.e., limited range of motion, decreased strength, poor coordination, motor planning difficulties) which can unfortunately result in long-term impairment and functional disability.

Motor …

Place, Culture, And Care: A Socioecological Examination Of Type 2 Diabetes Among Hispanics In The U.S., Danielle Montoya

Theses and Dissertations

Introduction: Type 2 diabetes (T2D) disproportionately affects U.S. Hispanic populations. This dissertation examined whether structural determinants fundamentally drive T2D disparities among Hispanics, with attention to within-group racial heterogeneity.

Methods: Three studies utilized nationally representative data. Study 1 examined neighborhood segregation and ethnic enclave residence associations with T2D using restricted NHANES data (2011-2018, n=5,056). Study 2 investigated acculturation and T2D associations using restricted NHANES data (2011-2018, n=4,540). Study 3 analyzed patient-provider racial/ethnic concordance and adequate diabetes care using MEPS data (2008-2021, n=17,138).

Results: Structural factors demonstrated primacy across all studies. Neighborhood segregation (aOR=1.17, p>0.05) and ethnic enclave residence showed no …

Opioid Tolerance And Withdrawal In The Mouse Colon, James Fune

Theses and Dissertations

Constipation is a major clinical obstacle associated with opioids, prompting patients to discontinue treatment due to pain, discomfort, and psychosocial stressors. Moreover, chronic users become tolerant to the analgesic effects of opioids, but not to their constipating effects. Upon cessation of long-term treatment, serious diarrhea–among other somatic signs of withdrawal–may ensue. These symptoms become a driving factor for relapse, causing patients to restart opioid treatment. In this study, we aim to understand mechanisms that contribute to opioid tolerance and withdrawal in the colon. Previous findings suggest that constipation occurs partly due to the colon’s lack of tolerance to opioids’ inhibitory …

Establishing A Conventional Linac-Based Electron Flash Beam, Justin Defrancisco

Theses and Dissertations

Problems: A rediscovered radiotherapy technique, FLASH, involves increasing the dose rate to >40 Gy/s. For a given dose, FLASH is shown to decrease the normal tissue complication probability without affecting the tumor control probability. More preclinical studies are necessary to confirm and enable these desirable properties on humans. Current preclinical investigations have diverse constraints, requiring FLASH apparatuses with flexible parameters and accurate control. However, there are limited FLASH platforms available, the existing ones are costly. Our institution is not in possession of any such infrastructure. Even if available, dosimetry and beam control in FLASH are extremely lacking. There is …

Understanding The Transitional Needs Of Servicemembers To Veterans: A Focus On Mental, Social, And Behavioral Health, Marieann C. Raguso

Theses and Dissertations

This applied dissertation was designed to fill the gaps on the transitional American veterans’ lived experience using their own voice. The reconstruction of an American Veteran’s identity after transitioning back into civilian life is a process with many challenges. Transitional practices often fail to help veterans to acculturate back into the civilian world. This includes the formulation of identities and associations. There is a lack of consistency in military transitional practices leading to identity loss and the formulation of mental and behavioral disorders. The aim of this study is to examine the lived experiences of veterans who have transitioned back …

Ecological And Pathological Applications Of The Heat Shock Response, Taylor Rae Stanley

Theses and Dissertations

The heat shock response (HSR) is a cytoprotective stress response pathway that regulates cellular proteostasis. The HSR is an evolutionarily conserved pathway that is essential for normal cellular functioning. Here, we explore the broad ecological and pathological impacts of the HSR. In an ecological context, we perform gene level analysis of the transcriptomes of two closely related sunfish. We found that the more invasive bluegill sunfish has gene expansions in two HSR gene families, the HSP70 family and the HSP90 family compared to the redear sunfish. These gene expansions were also observed in several other teleost fish species and were …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Investigation Of Reproductive Inhibition During Chronic Heat Stress In C. Elegans, Macy Makenna Nielander

Theses and Dissertations

Nearly all organisms experience heterogeneity in environmental conditions that can negatively impact fitness. A common adaptive strategy to reduce the impact of this stress is called facultative diapause, where development and reproduction are temporarily arrested to promote survival. Facultative diapause is characterized by three major criteria, the arrest must be (i) induced by an unfavorable environmental condition, (ii) reversible, and (iii) driven by genetically regulated mechanisms. The aim of this thesis was to determine whether chronic heat-induced inhibition of egg laying in Caenorhabditis elegans represents a novel form of facultative diapause. It was found that the inhibition of egg-laying is …

Regulation And Function Of The Rna-Binding Protein Khsrp During Neuronal Development, Regeneration And Axonal Injury Response, Courtney Nicole Buchanan

Theses and Dissertations

Axons, which extend long distances from neuronal cell bodies, rely on localized mRNA translation to swiftly respond to extracellular stimuli and physiological states. This work investigates the mechanism underlying the RNA-binding protein KHSRP’s, axonal mRNA translation and regulatory pathways involved in neuronal growth and regeneration. Our results indicate that KHSRP deletion in mice leads to upregulation of growth-associated mRNAs linked to neuronal morphology and function, resulting in increased axon growth and altered memory consolidation. Indicating a critical role for KHSRP in neuronal development and function through post-transcriptional regulation (Chapter 2). Additionally, we show there is a rapid increase in axonal …

Towards Understanding The Relationship Between Hearing Loss And Cognition In Healthy Aging, Samaneh Nemati

Theses and Dissertations

Age-related hearing loss (ARHL) has been increasingly linked to cognitive decline, both directly and through structural brain changes. This study utilized data from the Aging Brain Cohort project at the University of South Carolina (ABC@UofSC) to investigate the relationships between hearing impairments, cognitive performance, and gray matter volume across key brain regions. Specifically, the study aimed to: (i) examine the mediating role of gray matter volume in the relationship between ARHL and cognitive impairments; (ii) investigate the role of regional brain age gap in mediating the relationship between ARHL and cognitive decline; and (iii) delineate the distinctive impact of ARHL …

Information Exchange Through Social Networks Links To Adoption Of Child Feeding Practices In Nepal, Mohammad Masudur Rahman

Theses and Dissertations

While there have been notable decreases in child undernutrition (i.e., stunting) over the past few decades, it remains a major concern in Nepal, with 25% of children under the age of five experiencing chronic undernourishment. There is considerable scope for improving nutrition-related behaviors to address this ongoing issue. In Nepal, knowledge regarding appropriate child feeding practices is often inadequate, and thus additional sources of accurate information are required. Information through multiple sources (i.e., interpersonal communication, mass media, and mobile SMS) provides opportunity to reach households who inadequately practice childcare. Information improves knowledge and information exchange (i.e., receiving or sharing) usually …

Sex Differences In Active Avoidance And Neural Circuit Mechanisms In Contextual Fear Generalization, Carly Vincent

Theses and Dissertations

The current studies were aimed to investigate two behavioral hallmarks of anxiety and stress-related disorders, avoidance responses and the over-generalization of fear. In the first set of studies, active avoidance and extinction learning, that parallels exposure therapy in preclinical rodent models, were used. It is known that stress can influence aversive learning and extinction training, which can result in poor extinction retention. However, it is not well understood how the stress response is facilitating extinction resistance in active avoidance learning across sexes. Therefore, the first set of studies aimed to investigate the role of biological sex and glucocorticoid receptor (GR) …

Discovering Therapeutic Strategies In Colorectal Cancer Via Synthetic Lethal Genetic Screens On Patient-Derived Organoid Models, Sana Khalili

Theses and Dissertations

Precision medicine is a revolutionary approach of targeting genetic alterations that are present only in tumor cells to find vulnerabilities that can be targeted with therapy. Identifying genetic dependencies in human colon cancer could help identify effective treatment strategies. Genome-wide CRISPR-Cas9 dropout screens can reveal all genetic dependencies, some of which could be exploited as therapeutic targets using existing drugs.

In this dissertation, I comprehensively characterized genetic dependencies present in a colon cancer organoid avatar, and validated tumor-specific selectivity of select pharmacologic agents. I identified all somatic mutations, all expressed genes, and conducted a genome-wide CRISPR dropout screen to elucidate …

Factors Affecting The Transition From Pediatric To Adult Care Among Culturally Deaf Young Adults And Young Adults Who Are Deaf Or Hard Of Hearing, Anna Strickland Kell

Theses and Dissertations

Introduction: Adolescence to adulthood is marked by many transitions, including the transition from a pediatric to an adult medical home, also referred to as a health home. For young adults who are culturally Deaf, deaf, or hard of hearing, this transition may be complicated by population-specific needs related to language, literacy, and accessibility. Prior research with transition-age adolescents and young adults who are culturally Deaf, deaf, or hard of hearing has primarily focused on education or hearing health exclusively. The purpose of this research was to investigate the transition of health care from pediatric to adult services among culturally Deaf …

Mitochondrial Function In The Maternal Brain: A New Perspective On Gestational Stress And Pathology Of Postpartum Depression, Erin Rene Gorman-Sandler

Theses and Dissertations

Postpartum depression (PPD) is a major psychiatric complication of childbirth, affecting up to 20% of mothers, yet remains understudied. Mitochondria, dynamic organelles crucial for cell homeostasis and energy production, share links with many of the proposed mechanisms underlying PPD pathology. Brain mitochondrial function is affected by stress, a major risk factor for development of PPD, and is linked to avoidance and social behaviors. Considering the importance of mitochondria in regulating brain function and behavior, we hypothesized that mitochondrial dysfunction is associated with behavioral alterations in a chronic stress-induced rat model of PPD. Chronic mild unpredictable (CMUS) stress during late gestation …

The Role Of The Physical Therapist In Managing Type 2 Diabetes: Systematic And Qualitative Perspectives, Garrett Matthew Hainline

Theses and Dissertations

Introduction: Physical activity (PA) is an effective tool in the management of Type 2 Diabetes (T2D). PA recommendations for people with T2D are to achieve at least 150 minutes per week of moderate intensity PA. This assists to maintain blood glucose control and reduce cardiovascular disease risk factors. Unfortunately, people with T2D are less likely than their normoglycemic peers to meet PA recommendations.

Veterans of the armed forces experience T2D at even greater levels than the general population, with prevalence at about 20%. In addition, T2D and pre-diabetes are elevated among younger veterans, including those of recent conflicts. Reducing rates …

Early Intervention System Contextual Factors Contributing To Treatment Attendance And Clinical Outcomes, Anthony Eldridge

Theses and Dissertations

Early Intervention Programs (EI) are an established method of addressing and treating earlier childhood developmental problems that involves a system of complex processes which families must navigate to secure and maintain care. Extensive wait times and multiple service providers burdensome caregivers which may impact treatment engagement. Telehealth offers some clinical utility for improving EI service provision. However, little is known how system contextual factors predict a child’s Part B Eligibility and level of engagement with treatment. The primary aim of this study is to describe the effect that wait time, number of service providers, number of treatment services, and treatment …

Development Of A Haptic System For Robot-Assisted Femur Fracture Surgery, Fayez H. Alruwaili

Theses and Dissertations

Robot-assisted surgery has emerged within the field of surgical technology, driven by the need for greater accuracy and speed in the ongoing evolution of healthcare. This advancement has influenced numerous areas requiring enhancements to achieve optimal surgical results. However, surgical robotics tends to lack the surgeon’s connection to the operation, creating a gap in the intuitive skill set required for successful operations. The gap is seen through the lack of sense of touch, which may result in tissue damage and additional injury when the robot interacts with the patient. Furthermore, challenges faced during femur fracture surgery have positioned robot-assisted surgery …

Nanofiber-Hydrogel Composite Scaffold Fabrication Methods For Peripheral Nerve Regeneration, Jacob Lee Carter

Theses and Dissertations

Nerve graft conduits (NGCs) are a rapidly advancing field for treating peripheral nerve injuries that aim to guide the growth of regenerating axons across damaged gaps. A more effective NGC can be manufactured by combining the use of nanofibers to act as guidewires within a 3-D hydrogel that imitates the extracellular matrix of nerve tissue. Several methods have been developed to embed aligned nanofibers in an ordered architecture within a hydrogel matrix. The first method involves layer-by-layer additive manufacturing to create NGCs with rows of polycaprolactone (PCL) nanofibers surrounded by a gelatin methacrylate (GelMe) hydrogel in a 3-D structure. A …

Role Of Customized Visual And Multifactorial Interventions In Preventing Falls Among Individuals With Visual Impairment In South India, Ramya S

Theses and Dissertations

Falls are the second leading cause of unintentional injuries and extensively studied among the elderly. Hence, intervention studies for falls prevention are restricted to the elderly with or without visual impairment (VI). Even among studies with VI, strategies for treatable VI are widely explored. Hence this study aimed to understand falls and interventions that may reduce falls in all the age groups especially among those with untreatable VI.

This mixed methods study included identification of subjects aged ≥ 18 years with VI from clinical records of Medical Research Foundation, Chennai and details of previous history of falls were enquired over …

Improving Ligand Pharmacokinetics Via Bioisosteric Substitution Of Amides With 1, 2, 3-Triazoles While Maintaining Dopamine D4 Receptor Selectivity And Potency, Mohammad Alkhatib

Theses and Dissertations

Several neurophysiological functions, such as attention, cognition, and emotional regulation, are regulated by the binding of dopamine on G-Protein coupled receptors. D4Rs are mainly located in the prefrontal cortex and the hippocampus and are known to have a key role in decision-making, memory formation, cognition, and attention. Administration of D4Rs- selective ligands during the preclinical studies enhance the outcomes and the results in animal models suffering from neuropsychiatric disorders, including ADHD, substance use disorders (SUD), and Alzheimer's disease. Recently, we reported a group of D4R-selective ligands with different efficacies depending on their phenylpiperazine ring scaffold to illustrate D4R function during …

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.

Investigations On V2o5 And Its Derivative Nanocomposites For Photocatalytic Textile Organic Dye Degradation, Jenifer A

Theses and Dissertations

In recent times, organic dyes from industrial sludge become one of the significant causes of water contamination due to their utility in textile and paper manufacturing industries. These organic dyes are highly toxic and carcinogenic. Fortunately, the photocatalytic degradation process is a practical tool for decomposing toxic organic matter in wastewater by utilizing light. The photodegradation process can be performed using semiconductor materials to purify wastewater. Thus, semiconductor photocatalysis is a desirable alternative technique for decolorizing various organic pollutants.

In this context, the present work reports the preparation and characterization of V2O5 nanocomposites by facile methods and tests them against …

Multilevel Factors Affecting Covid-19 Vaccination Among African American Communities In South Carolina, Ran Zhang

Theses and Dissertations

Background: Persistent health disparities has led to significant public health challenges, especially for African American (AAs) communities, and have been exacerbated by the COVID-19 pandemic. Achieving high population vaccination rates are crucial to controlling the virus’ spread. However, AAs have higher rates of COVID-19 infection and mortality than Whites, yet their vaccination rates remain relatively low. The dissertation aimed to investigate the multilevel factors and mechanisms that affect AAs’ vaccination behavior. The first objective is to assess the impact of the intrapersonal level factor (i.e., perceived barriers to vaccination) on vaccination behavior. The second objective is to investigate the impact …

The Crucial Role Of The Ahr-Ilc3-Il22 Pathway In I3c-Mediated Protection Against Colitis And Associated Microbial Dysbiosis, Chandani Mitchell

Theses and Dissertations

Colitis is an inflammatory bowel disease characterized by dysregulation of the immune system that results in chronic inflammation and dysbiosis. Previously we showed that a naturally sourced aryl hydrocarbon receptor (AhR) ligand, indole-3-carbinol (I3C), was effective in the reduction of colitis-associated disease severity through innate lymphoid type 3 cells (ILC3s) in an interleukin-22 (IL-22) dependent manner. In one of our studies, we used single cell RNA sequencing (scRNAseq) analysis of colonic lamina propria cells from colitis models treated with I3C. Our results indicated that there were changes in the expressions of genes integral to IL-22 signaling when I3C was used …

Evaluating Nutrient Limitation Of Phytoplankton Growth In North Inlet Estuary, Sc, Catherine Schlenker

Theses and Dissertations

The biolimiting nutrients nitrogen (N) and phosphorus (P) are vital components of molecules essential to life. In marine systems, N:P ratios tend to follow the “Redfield ratio” of 16:1, which is often used to infer nutrient limitation of phytoplankton biomass. Traditionally, estuaries are thought to be N-limited (N:P < 16), but there have been increasing instances of P-limitation (N:P > 16) in coastal waters worldwide. Over the last few decades, nutrient loading in North Inlet Estuary (NIE) has changed such that dissolved inorganic nitrogen (DIN):dissolved inorganic phosphorus (DIP) ratios have increased by ca. 130%. This increase suggests that the estuary may be transitioning to N and P colimitation or primary P-limitation. We …

Neural Mechanisms Of Estrogen And Inflammation In Female Stress Susceptibility, Samantha Jane Bouknight

Theses and Dissertations

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are highly debilitating psychiatric disorders that notably share stress as an etiological factor. Stress is a common occurrence experienced daily by virtually everyone and, while most people are resilient, a substantial portion of the population exhibit risk factors that yield them susceptible to developing stress-related psychiatric disorders. One prominent factor that has long been known to increase this risk is the female biological sex with women presenting at least twice as often with disorders like PTSD and MDD compared to men. Interestingly, this bias exists distinctly during the reproductive years and …

Association Between Autoimmune Diseases And Lymphoma Risk Using The Uk Biobank, Hannah Grace Dice

Theses and Dissertations

Background. Lymphoma is a blood cancer that develops when white blood cells multiply in an abnormal way and collect in the lymph nodes. Autoimmune diseases result when the immune system is overactive, causing it to attack and damage the body’s own tissues. Limited studies have been conducted to investigate the association between autoimmune diseases and lymphoma risk.

Literature review. Based on prior research, six autoimmune diseases (rheumatoid arthritis (RA), lupus, Sjögren’s syndrome, sarcoidosis, Crohn’s disease, and ulcerative colitis (UC)) were examined to better understand their association with lymphoma risk. Prior research has concluded that certain aspects of these autoimmune diseases …

The Role Of Telehealth And Obstetrics Capacity On Maternal Health Care: A Mixed Methods Approach, Shanikque L. Barksdale

Theses and Dissertations

Background: The United States (US) is experiencing a maternal health crisis, with rising severe maternal morbidity and mortality rates and persistent racial, ethnic, and geographic disparities. While telehealth can address access challenges, there is limited evidence of its impact on access to maternity care and outcomes among rural and minoritized communities. The overall objective of this study was to analyze the disparities in maternal outcomes and user satisfaction by hospital-based telehealth and obstetric care availability.

Methods: A convergent parallel mixed methods approach was used. A multinomial logistic regression was used to analyze whether the changes in the proportions of hospitals …