Medicine and Health Sciences Commons^™

Investigating The Physiological Use Of An Organ-On-A-Chip Device Through The Design And Fabrication Of A Micro-Electrical Blood-Brain Barrier (Μe-Bbb) System, Amrita Srinivasan, Kiana Aran, Jonalyn Herce, Noor Chaudhry, Allexa Ortiz

CMC Senior Theses

Aging is considered the main risk factor for various neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Aging is associated with an increase in neuroinflammation, which is a significant contributor to cognitive impairment observed in these age-related neurodegenerative diseases. However, studying brain behavior remains a challenge due to the complex nature of isolating brain tissue from an organism. Modeling the brain allows for further study of these neurodegenerative diseases. Organ-on-a- chip (OoC), a system containing engineered or natural tissues grown within microfluidic chips, has emerged as a promising tool for mimicking human physiology in a controlled microenvironment. A …

Expansion On The Use Of The Novel Compound, Elp-004, Using A Mycobacterium Tuberculosis Experimentation Model, Kendyl Marie Berry

Graduate Theses, Dissertations, and Problem Reports

Osteoarticular tuberculosis (OAT) is a bone degenerative disease that results in bone erosion, joint effusion, joint swelling, and sometimes, nerve compression. OAT occurs from the hematogenous dissemination of Mycobacterium tuberculosis (Mtb) bacilli spreading from the primary site of infection to the bones and joints; the primary site of infection tends to be the lungs as pulmonary tuberculosis infections are the most common. OAT can occur as the result of an active or latent infection. Latent infections result in OAT when bacilli are able to escape granulomas. The incidence of OAT is not as high as pulmonary infections, making up about …

How Sleep Disturbances Affect Those With Borderline Personality Disorder And The Implications For Treatment, Molly L. Schmanke

Regis University Student Publications (comprehensive collection)

This thesis argues that there is limited research on Borderline Personality Disorder’s comorbidity with sleep disorders, and by pointing out the gaps in knowledge this will encourage researchers and doctors to consider this topic as important in the health care field. Sleep disorders can be anything from reduced total sleep time, fragmented sleep, and changes in sleep architecture, and all of these can cause and be caused by disruption of the circadian clock. There are various ways in which circadian clock disruption can cause diseases, cancer, and mental disorders through genes, sleep, and the environment. Borderline Personality Disorder comorbid with …

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …

Effects And Outcomes Of Different Laboring Positions And The Influence From Societal Norms, Amberlyn Heskett

Nursing | Senior Theses

Background

Within labor and delivery, every birth is different. Alarmingly, the U.S. has the highest maternal mortality rate, including death during labor, among developed countries (World Health Organization, 2022). Many maternal deaths may be preventable.

In the U.S., the use of forceps, vacuum-assisted birth, episiotomies, and emergency C-sections are common for women during childbirth. Even though some laboring positions may assist birthing more than others, there often is resistance to allowing various positions due to outside influences, including societal norms, hospital management, and healthcare professional training. Women in labor are vulnerable and look to their nurses for support during the …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Biomedical Applications Of Protein Films And Polymeric Nanomaterials, Sanjana Gopalakrishnan

Doctoral Dissertations

Biomaterials are widely applied for the diagnosis and treatment of numerous diseases. In addition to fulfilling specific biological functions, biomaterials must also be non-toxic, biocompatible, and sterilizable to be regarded as safe-for-use. Polymers are excellent candidates for fabricating functional biomaterials due to their wide availability and varied properties and may be natural or synthetic. Polymer precursors are fabricated into coatings, foams, scaffolds, gels, composites, and nanomaterials for several biomedical applications. This dissertation focuses on two types of polymeric biomaterials – protein-based materials and synthetic polymeric nanoparticles. Proteins are biopolymers that naturally occur with a variety of structural and functional properties. …

Roles Of Oxidative Stress And Dna Methylation In Cigarette Smoking-Induced Accelerated Acute Myeloid Leukemia Progression, Mary Figueroa

Dissertations & Theses (Open Access)

Acute myeloid leukemia (AML) is a commonly diagnosed cancer in smokers. When current or former smokers have AML, they have worse survival compared to never smoking patients. This has been observed clinically for decades, but then it is unknown how smoking leads to worsened AML survival. Smoking causes oxidative stress and altered DNA methylation that persists for decades in peripheral blood mononuclear cells, but these changes from smoking have not been evaluated in the context of AML. We hypothesize that smoking-induced molecular changes, including altered DNA methylation associated with poor AML prognosis, promote AML. We developed a novel model to …

Radioluminescence Based Biochemical Sensing And Imaging Strategies To Measure Local Drug Release And Ph, Gretchen B. Schober

All Dissertations

In this dissertation we describe methods for measuring infection relevant biochemical analytes using radioluminescent and ultrasound luminescent materials. Films and nanoparticles fabricated with europium doped gadolinium oxysulfide (Gd₂O₂S:Eu³⁺) are used to quantitatively measure radiolabeled pharmaceutical concentration, specifically tritium labeled vancomycin (³H-vancomycin). Europium and dysprosium doped strontium aluminate is used to fabricate an ultrasound modulated, pH sensing film. These methods are indicated for theranostic evaluation of implant associated infection. Bacterial biofilms are inherently resistant to traditional antibiotic treatment and can coat biomedical implants. These biofilm related infections are difficult or impossible to eradicate …

Ribonucleotide Reductase Subunit Switching In Hepatoblastoma Drug Response And Relapse, Anthony Brown

Theses and Dissertations (ETD)

Hepatoblastoma is the most common primary liver cancer in infants and young children. Despite being a very rare cancer that accounts for only 0.5-2% if all childhood cancer cases, HB has the largest increase in incidence among childhood cancers in the United States and worldwide. The five-year survival rate of children with the aggressive forms of HB, including those that have developed metastatic or recurrent diseases, is less than 40% due to the lack of effective treatment. We aim to identify targetable mechanisms underlying the progression and drug resistance of high-risk HB. Our recent work on HB mouse and organoid …

Nursing Perspectives And Opinions On Early Or Delayed Sepsis Treatment: A Mixed Methods Approach, Pamela L. Harris

Theses and Dissertations (ETD)

Purpose. Each year at least 1.7 million adults in America develop sepsis. Sepsis can lead to life threatening organ dysfunction, severe hypotension, and death when severe sepsis or septic shock is involved. Sepsis is responsible for 50% of acute kidney injury (AKI), which is the most common form of organ dysfunction seen in critical care. Sepsis associated AKI results in loss of, or decreased renal function, is associated with adverse long-term outcomes, and carries a higher mortality rate than non-septic AKI, sepsis without AKI, or septic shock without AKI. Surviving sepsis guidelines suggests a 1-hour window from the time of …

Otulin's Novel Regulatory Mechanisms In Genotoxic And Inflammatory Nf-Kb Signaling, Mingqi Li

Theses and Dissertations (ETD)

Triple negative breast cancer (TNBC) is aggressive but cannot be treated with hormone therapy or molecular therapy due to the lack of a target. Chemotherapy is a systemic treatment that works by attacking rapidly growing cells, which is initially more effective for TNBC patients than those individuals with the hormone receptor-positive breast cancer. However, patients with TNBC tend to develop resistance to chemo drugs, called chemoresistance. After years of effort, the signaling pathways involved in TNBC chemoresistance are gradually revealed, including the nuclear factor-kappa B (NF-kB) pathway. Transcription factor NF-kB is widely involved in cancer development and progression, and its …

Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib

Theses and Dissertations (ETD)

Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. Immunosuppressive myeloid cells comprise Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) and can suppress T cells via production of immunosuppressive factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs), mainly conventional dendritic cells (cDCs) and macrophages, to present or cross-present tumor antigens to T cells. Thus, targeting immunosuppressive myeloid cells while simultaneously enhancing APCs represents a promising strategy …

A Systematic Review Of Music Therapy For Children With Autism Spectrum Disorder, Alana Andrus

Honors Theses

Music therapy has been suggested to be effective in Autism. The purpose of this systematic review was to assess the effectiveness of music therapy as a potential treatment option for individuals with autism spectrum disorder, or ASD. To obtain published records, a PubMed search was conducted with the search term “music therapy autism,” which generated 187 studies. Each study was evaluated for relativity to the topic at hand. The remaining 151 articles were assessed for support status, as well as other later suggested research, in order to more confidently support music therapy as a treatment option for ASD patients. Approximately …

Leukocyte Subsets In The Peripheral Blood And Spleen Of Gastrointestinal Cancer Patients, Kathryn E. Cole

Theses & Dissertations

In 2022, an estimated 62,210 people will be diagnosed with pancreatic ductal adenocarcinoma (PDAC) and approximately 49,830 will die from the disease. Current treatment strategies for gastrointestinal (GI) cancer patients, such as PDAC, have shown limited benefit, suggesting the need to develop novel, multimodality therapeutic approaches. Adoptive cellular therapy (ACT) using autologous tumor infiltrating lymphocytes (TILs) has shown efficacy in patients with melanoma; however, this approach is costly and requires extensive cell culture for sufficient numbers of T-cells for infusion. GI cancer patients with borderline resectable disease, whose primary tumor is adjacent to the splenic vasculature, can sometimes undergo a …

Efficacy Of Δ-9-Tetrahydrocannabinol For Hiv-Related Neuropathic Pain, Kaia Horne

Honors Theses

Despite the availability and success of antiretroviral therapeutics, ~30% of patients living with HIV experience neuropathic pain that is often intractable. The mechanisms are not known, but there is evidence to support a role for the HIV virotoxins, Tat and/or gp120, which can damage or degenerate neurons and peripheral nerves. One mechanism by which Tat and gp120 promote nerve damage involves the stimulation of proinflammatory cytokine production from immune cells which can damage or kill bystander cells. Notably, compounds found in Cannabis exert anti-inflammatory effects and many studies report HIV patients to consume more marijuana than seronegative individuals. When people …

Targeting Metabolic Adaptations To Anti-Angiogenic Therapy In Ovarian Cancer, Deanna M. Glassman, Deanna Glassman

Dissertations & Theses (Open Access)

ABSTRACT

Background: Ovarian cancer is the most lethal gynecologic malignancy. Despite modest clinical improvements with anti-VEGF antibody (AVA) therapy, adaptive resistance is nearly ubiquitous and additional therapeutic options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance.

Purpose: To assess the efficacy of a glutaminase inhibitor as a means of exploiting the metabolic vulnerability of glutamine dependence that develops as a result of adaptive resistance to AVA therapy.

Experimental Design: We used a glutaminase inhibitor (GLSi) synthesized at MD Anderson Cancer Center for all in vitro and in vivo experiments. …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

“Translation Of Hdac6 Pet Imaging Using [18f]Ekz-001 – Cgmp Production And Measurement Of Hdac6 Target Occupancy In Nhps” – A Review, Dania Rahal

Chemistry & Biochemistry Undergraduate Honors Theses

The inhibition of histone deacetylase 6 (HDAC6) has been reported to alleviate the effects of neurodegenerative diseases such as Alzheimer’s disease. The brain-penetrant PET radioligand [¹⁸F]EKZ-001 has high affinity and selectivity towards HDAC6 and therefore suggests great promise in therapeutic treatment studies and development for neurodegenerative diseases. “Translation of HDAC6 PET imaging using [¹⁸F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs” has achieved an effective, fully automated method of producing [¹⁸F]EKZ-001 in compliance with current good manufacturing practices (cGMP) to support the translation of [¹⁸F]EKZ-001 PET for …

An Investigative Study Into Alzheimer’S Disease (Ad): Development, Pathway And Progression, And Novel Treatment, Aruha Khan

Chancellor’s Honors Program Projects

No abstract provided.

Targeting Protein Degradation To Uncover Novel Oncoprotein Drivers Of Acute Leukemia, Fatemeh Keramatnia

Theses and Dissertations (ETD)

Acute Lymphoblastic Leukemia (ALL), the most common childhood cancer and the second most common acute leukemia in adults, arises from clonal expansion of undifferentiated lymphoid precursor cells in bone marrow. Despite the extensive knowledge on its cytogenetic and molecular biology, ALL treatment remains highly challenging especially after relapse. Conventional chemotherapy has shown significant improvement in overall survival rates of pediatric patients up to 90%, however, treatment failure due to ALL relapse occurs in 15-20% of the cases. On the other hand, adults and elderly patients with ALL are considered difficult to treat populations with the 5-year overall survival of 30–40%. …

Current And Novel Neuroregenerative Therapies, Arrin Brooks

Theses, Dissertations and Capstones

Underlying the physical and cognitive deficits consequent of many neuropathologies is one common factor, the loss of neurons. While neurodegenerative diseases, stroke, and traumatic brain injury arise from a variety of etiologies, they all ultimately result in injury and/or death of neuronal cells and concomitant functional deficits. In the present work we primarily focus on current and potential treatments for localized lesions, particularly those in the striatum of Parkinson’s disease (PD) or the cortex as in stroke. First, we discuss a new surgical technique for deep brain stimulator (DBS) placement, as DBS is a mainstay treatment for movement disorders including …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Increasing Continuous Positive Airway Pressure Compliance With Various Telemedicine Interventions: An Integrated Literature Review, Tracy Partington

Doctor of Nursing Practice (DNP) Projects

Aims and Objectives. This literature review's objective was to synthesize evidence from previously published literature on telemedicine interventions' effectiveness on CPAP (Continuous Positive Airway Pressure) therapy compliance.

Background. It is estimated that 22 million Americans suffer from a form of Sleep Apnea (SA), and those up to 80 percent of the cases of moderate to severe Obstructive Sleep Apnea (OSA) are undiagnosed (Sleep Apnea, n,d). The first-line therapy for OSA is CPAP. However, CPAP therapy is associated with low compliance rates.

Design. Systematic review.

Method. A multi-database literature search was conducted to identify published literature between 2009 and 2020. …

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

Lgr5 Regulation Of Stat3 Signaling And Drug Resistance In Colorectal Cancer, Tressie Posey, Tressie Alexandra Posey

Dissertations & Theses (Open Access)

LGR5 Regulation of STAT3 Signaling and Drug Resistance in Colorectal Cancer

Tressie Alexandra Capri Posey B.S.

Advisory Professor: Kendra Carmon, Ph.D.

The greatest difficulty in treating colorectal cancer (CRC) is the development of drug resistance which leads to relapse after treatment and progression to metastasis. Cancer stem cells (CSCs) are believed to drive relapse because of their capacity to self-renew, acquire resistance mechanisms, and differentiate promoting tumor growth and heterogeneity. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is a bona-fide marker of CSCs and has been considered a viable target for CSC specific therapeutic development. While we showed targeting LGR5 …

Investigative Study Into Huntington's Disease: Development, Diagnosis, And Therapeutic Treatment, Allison N Mathews

Chancellor’s Honors Program Projects

No abstract provided.

Evaluation And Feasibility Of A Head Positioning Intervention In Patients With Intraparenchymal Hemorrhage, Wendy L. Dusenbury

Theses and Dissertations (ETD)

Stroke caused by intraparenchymal hemorrhage (IPH) is most commonly the result of hypertension-induced blood vessel rupture in the brain and is associated with devastating disability and high rates of death. To date, no intervention has improved outcomes in IPH stroke patients; however, head elevation may be one of the most important first steps to promote clinical stability in the hyperacute stage of IPH stroke because of the risk of increased intracranial pressure (ICP) in these patients. Nursing research completed in the late 1970s and early 1980s in patients with increased ICP due to traumatic brain injury showed that elevating the …

Role Of Limonene In An Experimental Model Of Rotenone Induced Parkinson’S Disease, Lujain Mohamad Bader Eddin

Theses

Parkinson's disease (PD) is one of the prevalent neurodegenerative diseases in elderly population. The symptoms of PD often begin with motor and cognitive impairment that are attributed to the dopaminergic neurons degeneration. Rotenone (ROT) is a naturally derived pesticide that is used in agriculture to control pests. It is a neurotoxin well-established for use in resembling PD symptoms in research. Limonene (LMN) is a plant derived monoterpene extracted from citrus peel with a wide range of therapeutic effects. Due to the shortage in available therapeutic agents that can cure or halt the progressive degeneration of PD, the main aim of …