Medicine and Health Sciences Commons^™

The Importance Of Protein Context In Spinocerebellar Ataxia Type 3, Sean Luis Johnson

Wayne State University Dissertations

Spinocerebellar Ataxia Type 3 (SCA3) is a member of the family of polyglutamine (polyQ) neurodegenerative disorders that includes Huntington's Disease and several other SCAs. SCA3, the most common dominant ataxia in the world, is caused by polyQ tract expansion in the protein, ataxin-3. How SCA3 occurs and how to treat it remain unresolved issues. The primary culprit of toxicity in all polyQ diseases is the glutamine repeat: its abnormal expansion leads to neuronal dysfunction and death. With that said, there is indisputable evidence that the way polyQ-dependent toxicity presents—areas impacted, cellular processes perturbed—is predicated in large part on regions outside …

Novel Interaction Of Cxcr4 And Pi4kiiiα In Prostate Cancer, Barani Govindarajan

Wayne State University Dissertations

The CXCR4-CXCL12 chemokine signaling axis plays a key role in migration and bone metastasis in prostate cancer (PC). Androgens regulate CXCR4 expression and its receptor activation in lipid-raft micro domains of PC cells, resulting in higher protease expression and invasion. In order to identify some novel CXCR4 co-regulators associated within the lipid-raft, a SILAC (Stable isotope labeling using amino acid in cell culture)-based proteomic analysis was performed with PC3 stable cell-lines over-expressing or knocking-down CXCR4. Phosphatidylinositol 4-kinase III alpha (PI4KIIIα or PI4KA) and SAC1 lipid phosphatase were identified as candidate proteins enriched in CXCR4 expressing cells. PI4KA is an evolutionarily …

Dancing The Storm: Neurobiological Correlates Of Trauma-Related Psychopathology In Youth Resettled As Refugees, And The Efficacy Of Creative Arts And Movement Therapies To Address Trauma-Related Psychopathology, Lana Ruvolo Grasser

Wayne State University Dissertations

Exposure to stress and trauma activates key adaptive pathways, including the sympathetic adrenomedullary system and the immune system, which can result in long-term health impacts of trauma especially when experienced during sensitive developmental periods. Alterations in these systems are measurable through non-invasive methods including skin conductance response (SCR), fear potentiated startle (FPS), and inflammation. Research regarding the impact of trauma, and more specifically posttraumatic stress disorder, has primarily focused on adults, and there is a paucity of neurobiological research in displaced populations—like refugees—who may experience higher rates of trauma exposure and related psychopathology. The present study measured SCR to a …

Backward Walking: A Novel Marker Of Fall Risk, Cognitive Dysfunction, And Myelin Damage In Persons With Multiple Sclerosis, Erin Edwards

Wayne State University Dissertations

Multiple sclerosis (MS) is a progressive, neurologic disease of the central nervous system that causes debilitating motor, sensory and cognitive impairments. As a result, persons with MS are at an increased risk for falls and falls represent a serious public health concern for the MS population. The current clinical measures used to assess fall risk in MS patients lack sensitivity and predictive validity for falls and are limited in their ability to capture to multiple functional domains (i.e., motor, sensory, cognitive and pathological domains) that are impaired by MS. Backward walking sensitively detects falls in the elderly and other neurologic …

Characterizing The Post-Translational Modifications Of The Pro-Oncogenic Type Ii Transmembrane Serine Protease Tmprss13, Carly Elizabeth Martin

Wayne State University Dissertations

TMPRSS13, a type II transmembrane serine protease discovered at the turn of the century, has recently been shown to be significantly overexpressed in both breast cancer (BCa) and colorectal cancer (CRC), and to mediate chemoresistance in cell lines from both cancer types. Furthermore, loss of TMPRSS13 in a genetic model of mouse mammary carcinoma significantly reduced tumor burden and growth rate, and increased overall tumor-free survival. Its location on the cell surface as well as its low expression in normal breast and colon make TMPRSS13 an attractive candidate as an oncogenic biomarker and therapeutic target in cancer. However, little is …

Hearing And Other Factors Influencing Memory Performance In Remote Assessment, Erika Squires

Wayne State University Dissertations

With the revitalization of aural rehabilitation (AR) and increased use of telepractice services, there is a paucity of research examining factors that have the potential to affect remote assessment. An assessment of memory is commonly included in a comprehensive AR assessment because recently developed auditory-cognitive training programs include auditory-based cognitive activities, such as auditory memory tasks. This investigation explored the effect of presentation modality on speech discrimination performance and whether self-reported hearing ability correlated with remote memory assessment in older adults.Older adults self-reported their hearing abilities and completed speech discrimination and memory tasks. Data were collected remotely via a telephone …

The Lived Experiences Of Muslim Women With Infertility, Samia Abdelnabi

Wayne State University Dissertations

Background: Infertility, ranked as the 5th highest global disability, is estimated to impact 180 million couples worldwide. Muslim couples associate parenthood or the ability to have children as an accomplishment in their marriage, adulthood, social status, and security in later life. A failure to conceive in Muslim societies may lead to stigma, social isolation, grief, and despair. There is a gap in the literature on how Muslim women perceive, understand, and cope with infertility in the U.S. This knowledge gap limits the ability in to understand how social, religious, and cultural practices impact a diagnosis of infertility on Muslim American …

Family Needs For Witnessing Ventilator Withdrawal In Intensive Care Units, Azzah Moubaraki

Wayne State University Dissertations

Background: Witnessing ventilator withdrawal and the subsequent death of a loved one in the ICU is a traumatic experience for family members, whose needs thus differ from those of other families in the ICU. Although various studies have noted the importance of preparing family members for ventilator withdrawal, based on retrospective interviews, little is known about which needs should be met, prospectively, to equip family members to witness and cope with ventilator withdrawal or about how sociodemographic characteristics affect those needs. Purpose: To prospectively determine the needs of family members who will witness a loved one undergo the process of …

The Changes In Dietary Patterns Of Saudi Women Residing In Saudi Arabia, South Korea, And The United States: The Effects Of Length Of Residency On Dietary Acculturation, Nouf Alharbi

Wayne State University Dissertations

ABSTRACT

THE CHANGES IN DIETARY PATTERNS OF SAUDI WOMEN RESIDING IN SAUDI ARABIA, SOUTH KOREA, AND THE UNITED STATES: THE EFFECTS OF LENGTH OF RESIDENCY ON DIETARY ACCULTURATION

by

NOUF ABDULLAH ALHARBI

August 2021

Advisor: Dr. Kai-Lin Catherine JenMajor: Nutrition & Food Science Degree: Doctor of Philosophy Given the large and growing numbers of Saudi individuals living abroad, examining how their dietary patterns have changed and influenced by acculturation with host countries, as well as the health consequences of these changes is a research area that needs to be investigated. The primary objectives of the present study were to compare …

An Emergent Legionnaires' Disease Syndemic: Water Supply Systems, Infrastructural Violence, And Afflicted Lives In The South Bronx, Ny, Eduardo Piqueiras

Wayne State University Dissertations

This dissertation examines how contemporary approaches to Legionnaires’ disease (LD) narrowly view it as a biomedical entity that obscures critical moral, temporal, and contextual dimensions creating gaps in how LD “cases” are defined and mitigated. Those who receive an LD diagnosis experience many unique challenges (e.g., personal, existential, community-based, and environmental) yet little is known about how this group of individuals experience recovery and attach meaning to their individual experiences. Using an anthropological lens of illness and recovery and a syndemics view of infrastructural violence this study examines those inadequately addressed multiple dimensions which limit our ability to confront the …

Exploring The Association Of Health Belief And Spiritual Coping With The Use Of Complementary Medicine By Parents Of Children And Adolescents With Cancer In Saudi Arabia, Logayn Hussamaldin

Wayne State University Dissertations

ABSTRACTExploring the Association of Health Belief and Spiritual Coping with the Use of Complementary Medicine by Parents of Children and Adolescents with Cancer in Saudi Arabia

byLOGAYN HUSSAMALDIN 2021 Advisor: Hossein N. Yarandi Major: Nursing Degree: Doctor of Philosophy Complementary and alternative medicine (CAM) is a term applied to treatments that are not part of conventional medicine, and in some cases, they may be used instead of conventional medicine. One national study and several international studies have identified the frequency of CM use in pediatric populations. The overall frequency of CM use among children in Saudi Arabia reached 87.8%-95% in …

Clinical Significance, Functional Role And Molecular Mechanism Of 2’-O-Methyltransferase Ftsj3 In Promoting Cancer Progression, Morenci Manning-Powell

Wayne State University Dissertations

2’-O-methylation (2’-O-Me), one of the most common modifications within RNA, has multiple roles in modulating RNA structure, stability, and interactions, as well as gene transcription and translation. We previously performed integrative genomic and transcriptomic analysis of 58 RNA methyltransferases, and identified FTSJ3 (FtsJ RNA 2ʹ-O-methyltransferase 3) as significantly amplified/overexpressed in breast cancer. Knockdown of FTSJ3 inhibits breast cancer cell growth in vitro. However, the clinical significance, functional role, and molecular mechanism of FTSJ3 in human cancer remains to be elucidated. In the present study, we first analyzed the differential mRNA and protein expression of FTSJ3 between tumor and normal tissues …

Modulation Of Pharyngeal Health In Bacterial Diet-Dependent Survival, Deniz Sifoglu

Wayne State University Dissertations

ABSTRACT

MODULATION OF PHARYNGEAL HEALTH IN BACTERIAL DIET-DEPENDENT SURVIVAL

by

DENIZ SIFOGLU

August 2021

Advisor: Dr. Joy Alcedo Major: Biological Sciences Degree: Doctor of Philosophy Both diet and bacterial microbiome modulate insulin signaling, which regulates key physiological processes that are important for survival. However, the mechanisms through which diet and the microbiome modulate insulin signaling remain unclear. To understand these mechanisms, I turned to the nematode worm C. elegans, whose diet consists of different types of bacteria. Like humans and other animals, C. elegans has to modulate its responses to its diet and to bacteria to optimize its survival. Because …

Hypochlorite-Mediated Oxidation Of Dopamine: Implications In Parkinson’S Disease And Manganism, Praneet Kaur Marwah

Wayne State University Dissertations

Both Parkinson’s disease and manganism (a condition caused by chronic exposure to excessive levels of manganese) affect the extrapyramidal system of the brain, disrupt dopaminergic signaling and cause similar motor symptoms. While there is no physiological explanation for the susceptibility of dopamine-rich regions of the brain in both disorders, dopamine itself is a likely candidate. Dopamine can undergo both enzymatic and spontaneous oxidation, and the principal product of dopamine oxidation in vivo is cysteinyl dopamine. We demonstrate here that hypochlorous acid, which is produced in the brain by the enzyme myeloperoxidase, converts cysteinyl dopamine into a neurotoxic dihydrobenzothiazine, DHBT-1, that …

Determinants Of Successful Diabetes Self-Management Behaviors Among Women Of Arab Descent With Type 2 Diabetes, Mona R. Alanzi

Wayne State University Dissertations

ABSTRACT

Type 2 Diabetes (T2D) continues to be an escalating public health problem that contributes to increased morbidity and mortality worldwide (American Diabetes Association, 2017b). According to the National Diabetes Statistics Report (2017), approximately 30.3 million (9.4%) Americans have T2D. It accounted for 252,806 deaths in 2015 in the United States. Although the complications of T2D is a major threat to the health of women of Arab descent, there is lack of information about the health practices and diabetes self-management behaviors of this population. The purpose of this dissertation is to examine the impact of diabetes knowledge, social/family support, acculturation, …

Mental Health Service Utilization Among Urban Adolescents: The Roles Of Perceived Mental Health Problems, Attitudes Towards Professional Help, And Stigma, Yi Tak Tsang

Wayne State University Dissertations

Mental health among adolescents is widely acknowledged as a significant concern in the United States. Based on a national survey, Merikangas et al. (2010) found that among 13-17 year olds, 42% to 48% reported experiencing mental health concerns. It is estimated that only half of adolescents with mental health problems utilize mental health services (Costello et al., 2014). An initial study found that caregivers of disadvantaged youth appeared to function as the “gatekeepers” to mental health services (Tsang et al., 2020). Also, the results suggested that positive attitude towards professional psychological help, but not stigma, predicted service enrollment. The current …

Age Differences In Hippocampal Glutamate Modulation During Associative Learning And Memory: A Proton Functional Magnetic Resonance Spectroscopy (1h Fmrs) Study, Chaitali Anand

Wayne State University Dissertations

Episodic and associative memory decline is one of the earliest cognitive impairments in normal aging and among the defining cognitive features of Alzheimer’s disease (AD). Since, age-related cognitive decline gradually devolves into AD, with neuropathology preceding cognitive changes by many years, the identification of biomarkers of early disease progression is crucial. Reduction in glutamate, the main excitatory neurotransmitter involved in associative memory, in key brain regions such as the hippocampus, has been theorized as one of the cellular mechanisms underlying cognitive decline in aging and AD. A few neuroimaging studies that demonstrated a link between older adults’ weaker cognitive performance …

Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog

Wayne State University Dissertations

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …

The Effects Of Postpartum Depression, Acculturative Stress, And Social Support On Mother-Infant Bonding Among U.S. Immigrant Women Of Arabic Descent, Darin Mansor Mathkor

Wayne State University Dissertations

Purpose and Background/Significance: The transition from “woman” to “mother” is a significant life event and can be extremely stressful when merged with the transition from ‘local’ to ‘immigrant’. The development of mother-infant bonding is considered a critical process in the postpartum period. Immigrant women have higher rates of PPD compared with women in their native countries. Among the general population, PPD is strongly associated with lower quality mother-infant bonding. Social support can play a central role in lowering the levels of PPD, and may contribute to higher quality of mother-infant bonding. Moreover, limited data suggests that acculturative stress is found …

Dynamic Resource Allocation For Coordination Of Inpatient Operations In Hospitals, Najibesadat Sadatijafarkalaei

Wayne State University Dissertations

Healthcare systems face difficult challenges such as increasing complexity of processes, inefficient utilization of resources, high pressure to enhance the quality of care and services, and the need to balance and coordinate the staff workload. Therefore, the need for effective and efficient processes of delivering healthcare services increases. Data-driven approaches, including operations research and predictive modeling, can help overcome these challenges and improve the performance of health systems in terms of quality, cost, patient health outcomes and satisfaction.

Hospitals are a key component of healthcare systems with many scarce resources such as caregivers (nurses, physicians) and expensive facilities/equipment. Most hospital …

Parametric Study Of Short Latency Vestibular Evoked Potentials In Healthy Young Adults, Sabahet Fatima Rizvi

Wayne State University Dissertations

The purpose of this study was to evaluate the feasibility of developing a novel approach of otolith assessment in humans. This approach used vestibular short-latency evoked potentials (VsEP) to evaluate some fundamental characteristics of VsEP responses in healthy young adults. Currently, measures for direct assessment of the otoliths are non-existent, as vestibular evoked myogenic potentials (VEMPs) rely on neck muscle contraction for cVEMPs or are a reflection of the vestibulo-ocular reflex (VOR) for oVEMPs, rather than the otoliths themselves (Fujimoto, Suzuki, Kinoshita, Egami, Sugasawa, & Iwasaki, 2018).

Stimuli consisted of bone-conducted vibrations elicited by a specialized vibrator (Bruel & Kjaer, …

Investigating Gray And White Matter Microstructure In Parkinson Disease Patients Using Diffusion Weighted Imaging, Wafaa Sweidan

Wayne State University Dissertations

Parkinson disease (PD) is a neurodegenerative disorder characterized histologically by the loss of dopaminergic neurons in the substantia nigra (SN), and clinically by motor symptoms. PD pathology extends beyond the SN, and involves the presence of intraneuronal inclusions in neuronal bodies (Lewy bodies) and dendrites (Lewy dendrites). A staging system for Lewy pathology has been proposed, where it is hypothesized that the disease initiates in the peripheral nerves system and spreads along a caudal-rostral pathway to the brain stem and the cerebral cortex. Histological and imaging studies highlight a role for cortical Lewy pathology and atrophy, respectively, in mediating the …

Development Of A Novel Cardiac Ischemia-Reperfusion Model In The Axolotl, Jeremy Tolentino Llaniguez

Wayne State University Dissertations

The Center for Disease Control’s National Center for Health Statistics data for mortality from diseases of the heart show the age-adjusted death rate has fallen from almost 600 deaths in the 1950s to just over 190 deaths per 100,000 U.S. residents today. With the recognized limitations of pharmacotherapy of myocardial infarction (MI), cell-based therapies have been undergoing rapid development and clinical testing. However, there is still no consensus about cell types, delivery routes, dosing and treatment schedules and pretreatment conditioning of cells prior to administration. Furthermore, a fundamental question remains unanswered about the reasons for the poor capacity for myocardial …

Nutrition And Health Status Of Hemodialysis Patients In Dhaka, Bangladesh, Tanjina Rahman

Wayne State University Dissertations

Methods to identify patients at risk for End stage renal disease (ESRD) are a high priority in Bangladesh, where kidney transplants/dialysis options are limited and costly. Every year, 35,000 to 40,000 people reach ESRD in Bangladesh, but currently available facilities can hardly accommodate only 9000 to 10,000 new patients with twice weekly dialysis and the remaining 66% have no access to any kind of renal replacement therapy (RRT) in the form of dialysis or transplantation. Nutrition is an important factor in maintaining good health of hemodialysis patients. However, data on nutritional status of Bangladeshi dialysis patients is limited and is …

Evaluating Historical Paradigms Of Sterility In Perinatal Microbiology And Ramifications For Pregnancy Outcomes, Jonathan Greenberg

Wayne State University Dissertations

Next-generation sequencing technologies, especially 16S rRNA gene and metagenomic sequencing have allowed investigations of low microbial biomass tissues of the human body. While these sequencing methodologies have provided large amounts of reliable data for higher microbial biomass sites, such as the mouth, intestine, and vagina, tissues of low microbial biomass sites are subject to specific caveats that were not appropriately considered in early investigations of these sites. Low microbial biomass sites of particular interest have included those of the reproductive and urinary systems. Utilization of DNA sequencing methodologies have allowed researchers to challenge existing paradigms of sterility around these sites …

Pilot Evaluation Of The Computer-Based Assessment Of Non-Cognitive Attributes Of Health Professionals (Cana-Hp), Sara Faye Maher

Wayne State University Dissertations

To meet the needs of complex and/or underserved patient populations, health care professionals must possess diverse backgrounds, qualities, and skill sets. Holistic review has been used to diversify student admissions through examination of non-cognitive attributes of health care applicants. The objective of this study was to develop a novel methodology, the computer-based assessment of non-cognitive attributes of health professionals (CANA­ HP), to effectively screen non-cognitive attributes of applicants. Three research questions were delineated; 1.) To determine the CANA-HP instrument reliability (internal consistency & interrater), 2.) To determine if the CANA-HP measured attributes of non­cognitive variables, as demonstrated by low construct …

Investigation Of Physiochemical Properties And Biocompatibility Of Amourphos Calcium Polyphosphate Hydrogel Doped With Antibiotics And Injectable Polymeric Dicalcium Phosphate Dihydrate Bone Cement, Yasaman Chehreghanianzabi

Wayne State University Dissertations

Amorphous calcium polyphosphate (ACPP) is an inorganic polymer ceramic. Here we use a simple method of preparing ACPP hydrogel in the presence of excess volume of water. Essentially, water availability to polyphosphate chains accelerates water molecule ingress and microstructural transformation of ACPP hydrogels. Antibiotic delivery capacity of ACPP hydrogel increases by the specific mixing and molding method, where the VCM has higher antibiotic encapsulation efficiency with the small burst release for the compressed discs. In part of this study, we investigate impact of ACPP hydrogel replacement by monomeric calcium phosphate on the quality of final product (dicalcium phosphate dihydrates (DCPD) …

Toward Enhancing Ecological Validity Of Cognitive-Linguistic Assessment: The Role Of Individual Differences In Cognitive Capacity On Oral Discourse Processing, Nancy Naperala

Wayne State University Dissertations

A growing body of multidisciplinary research indicates the need for more holistic tests of executive cognitive functioning and complex language metrics that predict real-life performance. However, empirical studies investigating cognitive aging, limited capacity processing and everyday discourse behaviours are still lacking. The present research focused on ecologically valid methods for capturing individual differences in cognitive capacity and the effects of cognitive load on oral discourse processing (ODP) in healthy adult participants. This methodology sought to tease apart the nature of capacity limits and provide a better estimate of age-related differences in everyday discourse behaviors in three parts. First, the effects …

The Role Of Bca2 In Regulation Of Warburg-Like Glucose And Lactate Metabolism In Breast Cancer Cell Lines, Richard T. Arkwright Iii

Wayne State University Dissertations

Modified metabolism is a hallmark of cancer cell biology known as “The Warburg Effect,” characterized by increased glucose-consumption and lactate-production, providing the metabolites and energy necessary for rapid proliferation. Breast-cancer-associated-gene-2 (BCA2) is an E3-Ub-ligase known to modulate AMPK, the “master-regulator of energy-homeostasis.” BCA2 is an oncogene associated with poor patient-survival and breast cancer invasiveness. Phospho-proteomic analysis of siBCA2-MDA-MB-231 knockdown-(KD) revealed enrichment of Nicotinamide-Nucleotide-Adenylyl-transferase-1 (NMNAT1), an essential enzyme in nuclear NAD-synthesis and a tumor-suppressor.

Initial experiments demonstrated that glucose concentration was positively correlated with BCA2 and inversely with NMNAT1 protein expression. shBCA2-KD in MDA-MB-468/-231 reproduced the inverse correlation between BCA2 and …

A Model Of Agitated Behavioral Symptoms In Persons With Alzheimer Disease, Katherine Kero

Wayne State University Dissertations

Background: Worldwide population trends are shifting with the population of Elders expected to dramatically increase in absolute and relative numbers in coming years. Alzheimer Disease (AD) is a common and costly disease of aging with agitation being the most poorly managed and detrimental behavioral symptom of the condition. The Nursing Theory of Unpleasant Symptoms provides a conceptual basis for understanding agitated behavioral symptoms associated with AD in the context of its antecedent causes and outcomes of the symptoms.

Purpose: The purpose of this dissertation was to model the predictors and outcomes of agitated behavioral symptoms in persons with AD. The …