Medicine and Health Sciences Commons^™

Cardioprotective Roles Of Hydrogen Sulfide Donor Treatment In Diabetic Cardiomyopathy, Sumit Kar

Theses & Dissertations

Diabetes mellitus (DM) increases the risk of heart failure 2-4-fold. Intensive glycemic control does not abate this risk in DM patients, suggesting that DM-induced heart failure is beyond hyperglycemia. DM silently induces cardiac muscle disorder termed diabetic cardiomyopathy (DMCM), which progresses to heart failure. The objective of this dissertation is to understand the mechanistic underpinnings of DMCM to develop new solutions to diagnose and treat heart failure in DM.

The heart pumps blood due to the contraction and relaxation of terminally differentiated cardiomyocytes with limited regenerative capacity. The DM environment of hyperglycemia, hyperlipidemia, and inflammation causes cardiomyocyte death and leads …

Beyond The Eye: The Neural Signature Of Cerebral Visual Processing In Children With Cerebral Palsy, Jacy R. Hannan

Theses & Dissertations

Cerebral palsy (CP) is a permanent, non-progressive neuromuscular disorder diagnosed early in childhood. Frequently the lesion that causes the motor impairments in individuals with CP concurrently disrupts the visual networks, placing them at a high risk of cerebral visual dysfunctions. Cerebral visual impairment (CVI) often remains unrecognized or misdiagnosed in people with CP. Despite the crucial role of visual function in the development of movement and cognition, the neurophysiological basis of the cerebral visual dysfunctions is almost entirely unknown. This investigation aimed to examine the neurophysiological mechanisms underlying cerebral visual dysfunction in children with CP. Specifically, this research used magnetoencephalographic …

Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo

Theses & Dissertations

Patients with cancer experience metabolic changes such as hypoglycemia, hyperglycemia, and glycemic variability; collectively termed malglycemia. Glycemic variability, defined as fluctuations in glucose, is a marker of metabolic instability. Higher glycemic variability is associated with adverse health outcomes in the general population and in those with diabetes. Little is known about glycemic variability in patients with cancer, especially those with solid tumor malignancies. Glycemic variability is associated with increased infection, shorter periods of remission, and higher mortality in patients with hematological cancer. This body of work describes the concept and measurement of glycemic variability to assess glycemic control in patients …

Impact Of Immunotherapy On The Survival Of Pancreatic Adenocarcinoma Patients: An Analysis Of The National Cancer Database, Saber A. Amin

Theses & Dissertations

Pancreatic adenocarcinoma (PDAC) represents 7.2% of all cancer deaths, and by 2030, it will become the second leading cause of death due to cancer. The median overall survival (OS) is 17-23 months in resectable and 4-6 months in metastatic PC [8-9]. The 5-year survival of resectable PC is 22%, and unresectable PC is 8%. A majority of patients treated with standard treatments such as surgery, chemotherapy, and radiation therapy eventually succumb to the disease due to widespread micrometastases at the time of diagnosis. Due to the minimal effect of the current treatments, novel treatment strategies such as immunotherapeutics have been …

Development Of An Lc-Esi-Ms/Ms Method For Determination Of A Novel Pyrrolomycin (Mp-1) And Application To Pre-Clinical Adme Studies, Wafaa N. Aldhafiri

Theses & Dissertations

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of a novel Pyrrolomycin (MP-1) in mouse plasma. MP-1 was extracted from plasma utilizing a structural analog (PL-3) as the internal standard (IS). Analyte separation was achieved using a Waters Acquity UPLC®BEH C18 column (1.7 µm, 100 x 2.1 mm) protected with Acquity UPLC C18 guard column. Mobile phase consisted of 0.1% acetic acid in water (10%) and methanol (90%) at a total flow rate of 0.25 mL/min. The mass spectrometer was operated at unit resolution in the multiple reaction …

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …

Characterization Of Novel Animal Models For Parkinson’S Disease, Mohannad Almikhlafi

Theses & Dissertations

Parkinson’s disease (PD) is neurodegenerative disorder characterized by dopaminergic neuronal loss in the substantia nigra (SN) pars compacta. Mutations in DJ-1, PINK1 and Parkin lead to PD in humans; however, in mice, mutations or knockout of these genes do not lead to disease. Development of small animal models mimicking PD pathogenesis would enable better understanding of the disease. Here, we examined two approaches using laboratory rats. First, DJ-1 knockout rats have been reported to develop movement disorders and loss of neurons similar to human PD. Comprehensive analysis of mitochondrial proteomic alteration in isolated synaptic mitochondria from DJ-1 knockout rats using …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma

Theses & Dissertations

Sympatho-excitation is a key characteristic in cardiovascular diseases such as chronic heart failure (CHF) and primary Hypertension (HTN). Evidence suggests that increased sympathetic tone is closely related to activation of the Renin-Angiotensin-Aldosterone system (RAAS) in the central nervous system. An underlying mechanism for sympatho-excitation is thought to be oxidative stress resulting from Angiotensin II (AngII) type 1 receptor (AT1R) activation. Over the past several decades, pharmacological targeting of components of the RAAS have been used as standard therapy in CHF and HTN. However, additional therapeutic strategies are necessary to control these diseases. Oxidative stress is regulated, in part, by the …

The Evolving Management Of Aortic Valve Disease: Trends In The Utilization And Cost Of Savr, Tavr, And Medical Therapy, Andrew Goldsweig

Theses & Dissertations

Aortic stenosis (AS) and regurgitation (AR) may be treated with surgical aortic valve replacement (SAVR), transcatheter AVR (TAVR), or medical therapy (MT). Data are lacking regarding usage and cost of SAVR, TAVR, and MT for patients hospitalized with aortic valve disease. From the Nationwide Readmissions Database, we determined utilization and cost trends for SAVR, TAVR, and MT in patients with aortic valve disease admitted 2012-2016 for valve replacement, heart failure, unstable angina, non-ST-elevation myocardial infarction, or syncope. From 2012 through 2016, there was a 48.1% increase in the number of patients hospitalized for aortic valve disease annually. Overall, 19.9%, 6.7%, …