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Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival, Rashmi Chandra

Wayne State University Dissertations

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy …

High Frequency Percussive Ventilation For Tumor Motion Immobilization, Ina Marina Sala

Wayne State University Dissertations

This work investigates the use of High Frequency Percussive Ventilation as a technique for respiratory motion mitigation in radiotherapy. This technique was extensively investigated in several prospective and retrospective studies.

In an initial prospective study, we evaluated the feasibility of HFPV and chest-wall motion reduction, by recruiting 15 healthy volunteers to undergo HFPV with three commercially available interfaces. For direct tumor motion immobilization, a second prospective study was performed in which with ten lung cancer patients underwent HFPV while imaged with high frame rate fluoroscopy. Diaphragm motion and image artifacts were quantified in a prospective study of a healthy volunteer …

Characterizing The Development Of Episodic Memory And Assessing The Reliability Of Fmri Measures, Lingfei Tang

Wayne State University Dissertations

The ability to remember past events is critical for everyday life and showed robust improvement over development from childhood to adulthood. With advances in noninvasive neuroimaging methods such as functional MRI in recent years, research efforts have been focused on identifying neural correlates underpinning developmental gains in memory performance. In my dissertation work, using a widely-validated subsequent memory paradigm, I aim to characterize functional MRI correlates of memory development. Specifically, I focused my investigation on identifying age differences in the functional patterns of two brain regions critical for memory, the prefrontal cortex and the hippocampus. Focusing on the prefrontal cortex …

Role Of Dyslipidemia On Lipid Metabolism In Maintenance Hemodialysis Patients, Eno Latifi

Wayne State University Dissertations

Maintenance hemodialysis (MHD) patients experience various abnormalities such as systemic inflammation (SI), oxidative stress (OS), and dyslipidemia (D). Defined as an imbalance of plasma lipids, lipoproteins, and lipid metabolism enzymes, D has been associated with a rise in morbidity and mortality within ESRD patients due to cardiovascular disease (CVD). However, the contribution of each of these parameters to D is poorly understood; moreover, the impact of the following parameters on dyslipidemia in different ethnicities is unknown. Hence, the objective of this study was to characterize D in a multi-ethnic cohort of ESRD patients. We hypothesized that the degree of dyslipidemia …

Strategies To Enhance The Anti-Leukemic Activity Of Venetoclax (Abt-199) In Aml Through Targeting Of Mcl-1, Daniel Luedtke

Wayne State University Dissertations

Acute Myeloid Leukemia (AML) is a frustratingly difficult to treat disease (67% 5 year survival for children and 24% for adults). The standard of care, similar to outcomes, has seen few improvements over the last several decades. The Bcl-2 family, which controls cell survival and apoptosis, is dysregulated in AML. Bcl-2, which is overexpressed in AML and associated with chemoresistance, is a promising therapeutic target. The now FDA approved venetoclax (ABT-199) is a BH3 mimetic that is able to bind to anti-apoptotic Bcl-2 and prevent it from sequestering pro-apoptotic Bim. While overall response rates are promising, our lab and others …

Development Of More Light Sensitive And Red-Shifted Channelrhodopsin Variants For Optogenetic Vision Restoration, Tushar Harishkumar Ganjawala

Wayne State University Dissertations

Discovery of channelrhodopsin (ChR), a light sensitive protein from green algae, has revolutionized the field of neuroscience research by empowering scientist to control neuron through the light, the technology popularly known as optogenetics. The ChR based optogenetics is one of the promising approaches for treating blindness caused by photoreceptor degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Fundamentally, the approach is about imparting light sensitivity to surviving inner retinal cells by ectopic expression of genetically encoded light sensitive proteins, such as ChR2. Although the concept of optogenetic approach has been proved by using ChR2, a major …

Condom Use Among Urban African American Adolescent Females, Jaquetta Marie Reeves

Wayne State University Dissertations

ABSTRACT

Background: Sexually transmitted infections (STIs) are one of the most common global health problems, having a profound impact on sexual and reproductive health worldwide. The CDC estimates that approximately 20 million new infections occur each year in the U.S., and almost half of them are among adolescents age 15–24. Despite government initiatives on STI prevention programs for adolescents, there is dearth of knowledge regarding the lack of condom use among adolescent high school students, especially concerning African American females who live in urban areas.

Purpose: The purpose of this research was to explore attitudes towards condoms, subjective norms and …

Novel Insights Into The Use Of Ercc1 As A Biomarker For Response To Platinum-Based Chemotherapy In Lung Cancer, Joshua Ryan Heyza

Wayne State University Dissertations

ERCC1/XPF is a DNA endonuclease with variable expression in primary tumor specimens, and has been investigated as a predictive biomarker for efficacy of platinum-based chemotherapy in non-small cell lung cancers where up to 30-60% of tumors harbor low to undetectable ERCC1 expression. The failure of an international, randomized Phase III clinical trial utilizing ERCC1 expression to predict response to platinum-based chemotherapy suggests additional mechanisms underlying the basic biology of ERCC1 in the response to platinum-DNA damage remain unknown. In this work, we aimed to characterize a panel of ERCC1 knockout cell lines generated via CRISPR-Cas9 where we identified a synthetic …

Sprouty4 Is A Negative Regulator Of Erk/Mapk Signaling In Breast Cancer And Plays A Role In The Transition From In Situ To Invasive Disease, Ethan Brock

Wayne State University Dissertations

Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Previous data by our group found that Sprouty4 transcript was differentially expressed between three DCIS cell lines and a non-transformed breast epithelial cell line. Sprouty proteins are important regulators of ERK/MAPK signaling, and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry we …

Inflammation In The Pathogenesis Of Diabetic Retinopathy, Haoshen Shi

Wayne State University Dissertations

The general purpose of these studies is to investigate inflammation in diabetic retinopathy in an effort to identify key intervention points to develop as treatments. Firstly, we showed that the neuropeptide VIP displayed protective immunoregulatory effects on retinal endothelial cells cultured under high glucose conditions. This effect was carried out, in part through the VPAC2 receptor.

Next, we studied the β-adrenergic receptor agonist, Compound 49b, and its effect on the pro-resolving RvD1 pathway. Compound 49b was previously shown to suppress both inflammatory and apoptotic responses in DR. We demonstrated that Compound 49b rescued the high glucose-induced decrese in RvD1 and …

Proactive Coordination In Healthcare Service Systems Through Near Real-Time Analytics, Seung Yup Lee

Wayne State University Dissertations

The United States (U.S.) healthcare system is the most expensive in the world. To improve the quality and safety of care, health information technology (HIT) is broadly adopted in hospitals. While EHR systems form a critical data backbone for the facility, we need improved 'work-flow' coordination tools and platforms that can enhance real-time situational awareness and facilitate effective management of resources for enhanced and efficient care. Especially, these IT systems are mostly applied for reactive management of care services and are lacking when they come to improving the real-time "operational intelligence" of service networks that promote efficiency and quality of …

Kilovoltage Intensity Modulated Radiotherapy, Brian Loughery

Wayne State University Dissertations

Contrast enhanced kilovoltage radiotherapy could be a significant improvement over the standard of care in glioblastoma multiforme, but its potential benefit has been hindered by fears of insufficient dose falloff, high skin and skull dose, contrast delivery concerns, and high cost. This dissertation aims to address the validity of these fears.

Contrast delivery concerns are examined by assuming that sufficient dose can be safely delivered to the tumor. Iodine, gadolinium, and gold nanoparticle biological effect and delivery research is examined and the ideal contrast delivery methods are reported. Dose falloff and skull dose are then investigated through treatment planning and …

Arabic Women’S Experience Of Childhood Sexual Abuse: A Mixed-Methods Study, Shahrazad Mahmoud Timraz

Wayne State University Dissertations

Background and purpose: Childhood sexual abuse (CSA) is an existing social problem that affects children worldwide, leading to poor psychological outcomes in adulthood. Childhood adversities including CSA account for 44.6% of childhood and 26%–32% of adult-onset psychiatric disorders. Furthermore, CSA is the second leading cause of posttraumatic stress disorder (PTSD) and influences an array of other outcomes such as depression, anxiety, hostility, and low self-esteem. Worldwide, approximately 8%–13% of girls have experienced sexual abuse. According to the few studies conducted in Arabic countries, CSA ranges from 7%–27%. Coping with CSA is a well-studied factor in regard to its impact on …

Data-Driven Modeling For Decision Support Systems And Treatment Management In Personalized Healthcare, Milad Zafar Nezhad

Wayne State University Dissertations

Massive amount of electronic medical records (EMRs) accumulating from patients and populations motivates clinicians and data scientists to collaborate for the advanced analytics to create knowledge that is essential to address the extensive personalized insights needed for patients, clinicians, providers, scientists, and health policy makers. Learning from large and complicated data is using extensively in marketing and commercial enterprises to generate personalized recommendations. Recently the medical research community focuses to take the benefits of big data analytic approaches and moves to personalized (precision) medicine. So, it is a significant period in healthcare and medicine for transferring to a new paradigm. …

Non-Invasive Mitochondrial Modulation With Near-Infrared Light Reduces Brain Injury After Stroke, Christos Dionisos Strubakos

Wayne State University Dissertations

Acute ischemic stroke is a debilitating disease that causes significant brain injury.

While rapid restoration of blood flow is critical to salvage the ischemic brain, reperfusion

of tissue can further drive brain damage by inducing generation of mitochondrial reactive

oxygen species (Chouchani et al., 2014a). Recent studies by our group found that noninvasive

mitochondrial modulation (NIMM) with near-infrared (NIR) light can limit the

production of reactive oxygen species following global brain ischemia (T. H. Sanderson

et al., 2018). NIR interacts with the rate limiting step of the mitochondrial electron

transport chain (ETC), cytochrome c oxidase (COX), and modulates mitochondrial

respiration. …

Characterizing Novel Radiologic And Pathologic Tissue-Based Risk Factors For Breast Cancer In African American Women With Benign Breast Disease, Asra N. Shaik

Wayne State University Dissertations

African American women (AAW) suffer a higher breast cancer mortality burden than women of other ethnicities in the US. More likely to be diagnosed with aggressive subtypes resistant to therapy and with rapidly fatal course than European American women (EAW), AAW may benefit greatly from earlier detection of breast cancers. However, it remains difficult to predict with a high degree of accuracy which women will develop breast cancer. Current risk assessment is especially poor for AAW, where models consistently underestimate risk in the subset of women with a prior biopsy. Risk assessment can be improved with the inclusion of new …

The Adaptation To Head And Neck Cancer In The Veteran Population, Diane Marie Sobecki-Ryniak

Wayne State University Dissertations

ABSTRACT

ADAPTATION TO HEAD AND NECK CANCER IN THE VETERAN POPULATION: A PILOT STUDY

By

DIANE SOBECKI-RYNIAK

December 2018

Advisor: Dr. Margaret Campbell

Major: Nursing

Degree: Doctor of Philosophy

Post-traumatic stress disorder in the head and neck cancer veteran population may present a challenge to adaptation during diagnosis and treatment of illness. The evaluation of post traumatic stress disorder, anxiety, depression and quality of life were examined and correlated against symptom occurrence and triggering of post traumatic symptoms across experiences. A significant correlation between PTSD-C and PTSD-S was found (r = 0.91, p = 0.001); there was a non-significant correlation …

Managing Operational Efficiency And Health Outcomes At Outpatient Clinics Through Effective Scheduling, Samira Fazel Anvaryazdi

Wayne State University Dissertations

A variety of studies have documented the substantial deficiencies in the quality of health care

delivered across the United States. Attempts to reform the United States health care system in the 1980s and 1990s were inspired by the system's inability to adequately provide access, ensure quality, and restrain costs, but these efforts had limited success. In the era of managed care, access, quality, and costs are still challenges, and medical professionals are increasingly dissatisfied.

In recent years, appointment scheduling in outpatient clinics has attracted much attention in

health care delivery systems. Increase in demand for health care services as well …

The Impact Of Neonatal Pain And Reduced Maternal Care On Brain And Behavioral Development, Sean Michael Mooney-Leber

Wayne State University Dissertations

In the neonatal intensive care unit (NICU) preterm infants are exposed to a multitude of stressors, which include both neonatal pain and reduced maternal care. Clinical and preclinical research has demonstrated that exposure to neonatal pain and reduced maternal care has a profound negative impact on brain and behavioral development. Currently, the biological mechanism by which both of these stressors impacts brain and behavioral outcomes remains widely unknown. To uncover a potential biological mechanism, the current dissertation project utilized a preclinical model of repetitive needle pokes and developed a novel model of reduced maternal care through tea-ball encapsulation. Briefly, rat …

The Influence Of Protein Context On Polyglutamine Toxicity In Spinocerebellar Ataxia Type 3, Joanna Rae Sutton

Wayne State University Dissertations

The polyglutamine (polyQ) disease family is composed of nine neurodegenerative diseases caused by CAG trinucleotide repeat expansions in the associated genes. Although these diseases are caused by similar mutations, the polyQ proteins are otherwise structurally and functionally unique. Thus, the protein domains surrounding the polyQ tracts, as well as their interacting partners, are thought to be critical to the pathogenesis of these clinically distinct diseases. Spinocerebellar ataxia type 3 is caused by polyQ expansion of ataxin-3, a deubiquitinating enzyme implicated in protein quality control, transcriptional regulation, and DNA repair. Rad23 and VCP are two of ataxin-3’s protein quality control partners …

Improving Aav Transduction Efficiency In Retinal Bipolar Cells For Optogenetic Vision Restoration, Shengjie Cui

Wayne State University Dissertations

Recombinant adeno-associated virus (AAV) vectors are the most promising vehicles for therapeutic gene delivery to the retina. We are developing AAV-mediated expression of optogenetic tools in surviving inner retinal neurons as a potential strategy to restoring vision after the death of photoreceptor cells in retinal degeneration. Targeting optogeneitc tools, such as channelrhodopsin-2 (ChR2), to retinal bipolar cells (RBCs) is particularly attractive. In particular, our lab has recently developed an optimized mGluR6 promoter-based virus vector that can mainly target ChR2 to rod bipolar cells. However, AAV-mediated transduction efficiency in RBCs is relatively low. The transduction efficiency could be affected by a …

The Role Of Neurokinin Receptors And Satellite Glial Cells In Herpes Simplex Virus 1 Latency, Andrew Jerome

Wayne State University Dissertations

The ability of herpes simplex virus 1 (HSV-1) to establish a lifelong infection in neurons of the trigeminal ganglion (TG) make it a constant public health threat. Viral reactivation from its latent state is currently the leading cause of viral induced blindness in the United State, as well as the leading cause of herpes simplex encephalitis. Unfortunately, how the virus is able to both establish and maintain its latent state in the TG is not well understood. The purpose of this work was to better understand how neuropeptide signaling through neurokinin receptors, as well as how satellite glial cells (SGCs) …

Venous Thromboembolism (Vte) Harm Measurement And Risk Assessment In Real-Time Using Electronic Health Records(Ehr), Seyed Mani Marashi

Wayne State University Dissertations

Venous Thromboembolism (VTE) is a deadly disease and is considered as one of the top reasons for avoidable hospital deaths in the United States and around the world. Patients who survive this disease often must face life-long complications such as Post-thrombotic syndrome (PTS), Chronic thromboembolic pulmonary hypertension (CTPH), etc. Therefore, it is important to monitor and reduce the number of VTE instances in hospitals. This study shows how Electronic Health Records (EHRs) can be utilized to achieve this goal.

First, a new near real-time VTE harm measurement model was developed. Not only the developed model can deliver near real-time results, …

Functional Analysis Of Rad6 In Brca1 Wild Type And Brca1 Mutant Triple Negative Breast Cancer Drug Response, Brittany Haynes

Wayne State University Dissertations

TNBCs account for 15-20% of all breast and are unsuitable for common targeted therapies as they lack expression of estrogen, progesterone, and Her2/neu receptors. Cisplatin, a DNA damaging agent, is currently under clinical investigation for treatment of TNBCs and paclitaxel, a mitotic spindle poison, is a first-line treatment option for this disease. While both agents elicit therapeutic benefit BRCA1 mutation status, toxicity, and resistance are limiting factors. Rad6 functions as an E2 ubiquitin conjugating protein and its enzymatic activity is critical for its cellular function. Rad6 is known to play a critical role in the translesion synthesis (TLS) damage response …

Mechanisms Of Hormonal Regulation Of Invasiveness And Metastasis Of Luminal Breast Cancer, Thomas Mcfall

Wayne State University Dissertations

ABSTRACT

MECHANISMS OF HORMONAL REGULATION OF INVASIVENESS AND METASTASIS OF LUMINAL BREAST CANCER

By

THOMAS MCFALL

December 2017

Advisor: Dr. Manohar Ratnam

Major: Cancer Biology

Degree: Doctor of Philosophy

Over 20% of breast cancer cases present with distal metastasis and they are predominantly of luminal subtypes. As luminal breast cancer is relatively indolent, it is believed that progression to metastasis must occur over many years, generally well into post-menopausal years. Unfortunately, very little is known about the mechanisms by which these hormone receptor positive tumors metastasize, likely in part due to their slow metastatic rates in animal model systems as …

Commissioning And Validation Of Analytical And Monte Carlo Based Dose Calculation Algorithms For Proton Spot Scanning, Jatinder Saini

Wayne State University Dissertations

Purpose: Accurate dose calculation is one of the most necessary components of radiation therapy. While the commercially available photon dose calculation algorithm offerings have improved considerably in last decade, proton dose calculations are still performed using the analytical dose calculation algorithms. The goal of this work is to validate a newly available commercial Monte Carlo (MC) dose calculation algorithm using measurements and simulations in GATE software. A secondary goal is to compare and contrast the performance of analytical algorithm against MC algorithm. Finally, GATE simulations are used to evaluate a newly available ceramic marker for ocular melanoma proton therapy.

Methods: …

Arab American Adolescents’ Bullying Experiences And Effects On Their Perceived Stress And Health, Maha Albdour

Wayne State University Dissertations

This study is intended to examine the bullying experience among Arab American adolescents and effects on their perceived stress and health. Adolescents who are vulnerable or marginalized might be at higher risk for bullying. Arab American adolescents have not been included in research studies examining bullying and described as the invisible population.

The Neuman System Model, which focuses on wellness of adolescents in relation to environmental stress, guided this study. Bullying is a tension producing stressor, operationally defined as repeated attacks or intimidation that cause fear, distress or harm and perceived power imbalance between bully and victim. Perceived stress is …

Middle School And High School Students Who Stutter: A Qualitative Investigation Of School Experiences, Tiffany Cobb

Wayne State University Dissertations

ABSTRACT

MIDDLE SCHOOL AND HIGH SCHOOL STUDENTS WHO STUTTER: A QUALITATIVE INVESTIGATION OF SCHOOL EXPERIENCES

by

TIFFANY COBB

MAY 2017

Advisor: Dr. Derek Daniels

Major: Speech-Language Pathology

Degree: Doctor of Philosophy

Purpose: The purpose of this study was to explore and further understand the ways in which middle school and high school students perceive their school experiences within the school environment.

School has an important impact on the social development of children (Milsom, 2006). Learning is not done individually as classrooms are inherently social places. This suggests that students do not learn alone, but rather in the presence of many …

Assessing Parent Invovlment In Applied Behavior Analysis Treatment For Children With Autism, Krista Marie Clancy

Wayne State University Dissertations

The purpose of this study was to compare two groups of parents whose children participated in ABA on their levels of stress, self-efficacy, treatment acceptability, and parents’ level of involvement in their children’s treatment, and to assess variables that may explain variance in parent involvement. Parents in the treatment group participated in a voluntary parent training (n=18) and the comparison group were parents who elected not to participate in the voluntary training (n=22). This was a quasi-experimental design study where parents and their therapists completed a survey regarding parents’ involvement in their children’s treatment programs. Additional parent measures collected as …

Brain Connectivity After Concussion, Armin Iraji

Wayne State University Dissertations

Mild traumatic brain injury (mTBI) accounts for over one million emergency visits in the United States each year. While most mTBI patients have normal findings in clinical neuroimaging, alterations in brain structure and functional connectivity have frequently been reported. In this study, we investigated the large-scale brain structural and functional connectivity using diffusion MRI and resting-state fMRI data. Data from 40 mTBI patients was acquired at the acute stage (within 24 hrs after injury). 35 patients returned for data acquisition at a follow-up (4-6 weeks after injury). Data was also collected from a cohort of 58 healthy subjects, 36 of …