Medical Sciences Commons^™

Terahertz Electromagnetic Effects And Chirality-Induced Spin Selectivity In Dna, F. Matthew Mihelic Md

Faculty Publications

The effects of terahertz electromagnetic stimulation of the DNA molecule can be understood through modeling of the quantum logical mechanics of the DNA molecule.  Coherent conduction of electron spin states along the aromatic nucleotide base pairs and chirality-induced spin selectivity are two characteristics of the DNA molecule that are involved in the precise separation of the double-stranded DNA molecule at a specific location.  Such modeling can inform predictions of DNA strand separation and has significant implications for understanding DNA transcription bubble formation.

Sugammadex For Reversal Of Neuromuscular Blocking Agents Versus Neostigmine - Safety Comparison, Amanda K. Butler, Daniel Belu, Bailey Accardo, Courtney Ayana Bullard, Tracy Mcclinton Dnp, Aprn, Agacnp-Bc, Hget-C, Ebp-C, Dwayne Accardo Dnp, Crna, Faana

Doctor of Nursing Practice Projects

Purpose/Background

Sugammadex and neostigmine are two common drugs used to reverse neuromuscular blockade in anesthesia, but they differ in mechanism of action, side effects, and cost.

Sugammadex provides rapid reversal, has fewer side effects, and has a lower risk of bradycardia than neostigmine. This scoping review examines the frequency of bradycardia in adult surgical patients receiving sugammadex versus neostigmine.

Methods

A scoping review was completed of peer-reviewed articles comparing the incidence of bradycardia in adult surgical patients after the administration of sugammadex and neostigmine for neuromuscular blockade reversal. Findings indicate that sugammadex resulted in fewer adverse events, including bradycardia, than …

Deciphering Genotype-Phenotype Connections: Leveraging Pangenomes And Comprehensive Genome Variation, Flavia Villani

Alternative Theses and Dissertations (AETDs)

My thesis explores the application of advanced techniques for discovery of genetic variation and pangenomic approaches to enhance our understanding of genetic variation and genotype-phenotype relationships in two key model organisms: the HXB/BXH recombinant inbred rat family and the BXD mouse family. Through deep sequencing and innovative computational methods, I constructed com- prehensive pangenome graphs that captured genetic diversity beyond what is accessible through conventional single-reference approaches. In the HXB rat family, I identified approximately 200 million base pairs of sequence absent from the reference genome and discovered novel variants associated with glucose metabolism and chromogranin expression through phenome-wide association …

Synthesis And Design Of Clpp Activators As Novel Antibiotics, Schyler Odum

Theses and Dissertations (ETD)

Purpose. Design and synthesize novel compounds to treat Staphylococcus aureus infections by targeting the dysregulation of the Casein Protease P, ClpP. Methods. Utilize established chemical methods to synthesize ureadepsipeptides, small-molecule ClpP activators, and ureadepsipeptide hybrids. Assess their effectiveness by using minimum inhibitory concentration assays and in vitro biochemical assays for ClpP activation. Explore their potential as antibiotics through mitochondrial toxicity tests, glucose/galactose assays, and biophysical measurements related to metabolism and clearance, including thermal shift and surface plasmon resonance assays. Results. Synthesized and tested 33 novel compounds, comprising a total of 80 synthetic steps. Conclusion. The three-part conclusion from the dissertation …

The Role Of Epigenetic Aberrations In The Cold Tumor Phenotype And Inflammatory Signaling In High-Risk Neuroblastoma, Pamela Morgan Watson

Alternative Theses and Dissertations (AETDs)

Neuroblastoma (NB) is a highly aggressive, heterogeneous disease that arises from the sympathetic nervous system (SNS) and originates from neural crest cells (NCCs) (1). NB is the most common extracranial cancer in pediatric accounts for 15% of pediatric cancer deaths (2). This high mortality rate is the result of the metastatic, immune evasive, and treatment resistant characteristics of the disease (3). It has been proposed that NB arises from blocks in differentiation during development, resulting in a mixture of two distinct cell types within the tumor: mesenchymal and adrenergic (Figure 1.1) (4,5). The adrenergic cell type is more differentiated, and …

Aging Skeletal Muscle: Influence Of Obesity And Role Of The Exercise Responsive Nuclear Receptor Nor-1, Hector G. Paez

Alternative Theses and Dissertations (AETDs)

Skeletal muscle mass and function are critical components of overall health and quality of life. Advanced age is associated with skeletal muscle disease characterized by a loss of muscle mass, function, and quality. Indeed, low muscle mass and function is associated with poor disease outcomes and greater mortality, greater incidence of falls, and a high fiscal and societal cost. Aging contributes to a decline in skeletal muscle health through several intrinsic and extrinsic mechanisms including impaired nutrient sensing, mitochondrial dysfunction, inflammation, physical inactivity, and proteostatic imbalance. Obesity, an increasingly prominent public health concern, is becoming more common in the elderly …

The Role Of Skeletal Muscle Ampk/Mtorc1 Signaling In Disrupted Metabolism During Chemotherapy Treatment And Recovery, Jessica L. Halle

Alternative Theses and Dissertations (AETDs)

Colorectal cancer patient survival rate has increased over the past decade due to improved screening and treatment options. The clinically relevant FOLFOX (5-fluorouracil [5-FU], oxaliplatin, leucovorin) chemotherapy regimen is a mainstay treatment option, despite the development of severe side-effects that can occur acutely or develop as a late effect after treatment cessation. Cancer and chemotherapy can promote systemic metabolic dysfunction; consequently, patients will likely experience debilitating weakness and fatigue, and these symptoms are often accompanied by excessive fat and muscle loss. Although studies have established chemotherapy effects on the tumor, few have investigated mechanisms underlying the metabolic complications associated with …

The Role Of Microrna-152 In The Pathogenesis Of Diabetic Cardiomyopathy, Joy Olaoluwa Gbadegoye

Alternative Theses and Dissertations (AETDs)

Diabetes mellitus, one of the world’s fast-growing diseases, is characterized by high death rates from cardiac complications named diabetic cardiomyopathy (DCM). DCM is a heart disease that occurs in both type 1 and 2 diabetes mellitus patients. Many management options have been explored in the management of DCM, including ACE inhibitors, beta-blockers, etc.; however, limited success has been recorded from these. MicroRNAs, recently discovered gene regulators, have been reported to be associated with various physiology and pathological processes in the mammalian body. These include cell proliferation, cell death, senesis, carcinogenesis, diabetes, and heart failure, among others. Various miRs have been …

A Quantum Logic Gate In The Dna Deoxyribose Moiety, F. Matthew Mihelic

Faculty Publications

The deoxyribose moiety of a nucleotide in the DNA molecule can act as a quantumlogic gate, in which the enantiomeric shift between the C2-endo and C3-endo conformations of each nucleotide, occurs within a logically and thermodynamically reversible situation of electron spin qubits, that are coherently held within the topologically insulating DNA crystalline nanostructure, and that are coherently conducted along the delocalized electrons of the pi-stacked nucleotide base pairs. The enantiomeric symmetry between the C2-endo and C3-endo conformations is logically and thermodynamically reversible because it functions as a symmetry-breaking Szilard engine that is effectively built out of the physicality of the …

Wnt5b As A Therapeutic Target For Osteosarcoma Stemness, Metastasis, And Chemoresistance, Rachel S. Perkins

Alternative Theses and Dissertations (AETDs)

Osteosarcoma is a pediatric bone cancer that has no targeted therapy and has had no treatment advances for the last three decades. Osteosarcoma frequently metastasizes to the lungs and is highly chemotherapy resistant, reducing patient survival with metastatic disease to 20% after 5 years. New therapies targeted to metastasis and drug resistance in osteosarcoma are essential to improving patient outcomes.

Osteosarcoma is a pediatric bone cancer that has no targeted therapy and has had no treatment advances for the last three decades. Osteosarcoma frequently metastasizes to the lungs and is highly chemotherapy resistant, reducing patient survival with metastatic disease to …

The Impact Of Local Physiology On The Corrosion Of Orthopedic Alloys, Madison Nicole Brown

Theses and Dissertations (ETD)

Introduction. Total knee arthroplasty (TKA) is used in the treatment of end-stage osteoarthritis of the knee. It is one of the most common elective surgeries performed with predictions expecting significant increases in the number of procedures performed over the next decade. However, the patient satisfaction rate after TKA is as low as 80%. Cobalt-chromium-molybdenum (CoCrMo) is regularly used for TKA protheses due to the alloy’s mechanical strength, biocompatibility, and corrosion resistance. The corrosion resistance of this alloy relies on a passive oxide layer. This oxide layer can be impacted by phagocytic cells which can leave pits and craters on implant …

Taste And Learning In The Gustatory Cortex, Martin Raymond

Alternative Theses and Dissertations (AETDs)

This research investigates the organization of taste representations in the gustatory cortex (GC) through two experiments utilizing miniscope imaging in mice. The first experiment focuses on conditioned taste aversion (CTA) and reveals that taste representations in GC are heavily dominated by palatability, with shifts in representational space occurring as a function of learning and extinction. The second experiment explores the interrelation of aversive stimuli, the impact of novelty on taste representations, and the role of somatosensory feedback. Findings suggest that familiarity and palatability emerge as positive signals with experience, shaping taste representations in GC. The study contributes to a nuanced …

Biomechanical Outcomes Of Distinct Tka Surgical Alignments And Implant Designs, Alexis Kathleen Nelson-Tranum

Theses and Dissertations (ETD)

Introduction. Total knee arthroplasty (TKA) has advanced over the past two decades from traditional post-operative neutral alignment methods with an overall goal of implant longevity to ones that are more personalized to better replicate individual native knee kinematics. Personalizing TKA knee kinematics to better replicate a patient’s native knee kinematics has evolved in response to a reported 20% dissatisfaction by patients with their TKA. These personalization advancements include innovations in surgical alignment techniques include the kinematic alignment (KA) and joint line obliquity (JLO) restoration, in contrast to the mechanical alignment (MA) technique that places everyone into the same mold. Additionally, …

Characterizing The Cellular Response To Astrovirus Infection In The Central Nervous System, Amy E. Davis

Theses and Dissertations (ETD)

Central nervous system (CNS) diseases caused by infectious agents pose significant health challenges, often leading to severe neurological dysfunction with high morbidity and mortality rates. Astroviruses (AstVs), traditionally known for causing gastroenteritis, have recently been identified as neuroinvasive pathogens capable of inducing neurological diseases. This study explores the cellular and molecular mechanisms by which AstV, specifically non-classical VA1 and classical HAstV1 genotypes, induce CNS pathology in human neurons and astrocytes. Utilizing primary human neurons and astrocytes from various brain regions, this research investigates the cytotoxic effects, apoptotic pathways, and inflammatory responses triggered by these viruses. This study reveals that VA1 …

Pan-Cancer Genomic Characterization Of Human Papillomavirus Associated Tumors, Jeremiah Ray Holt

Theses and Dissertations (ETD)

Infection with high-risk human papillomavirus (HPV) accounts for nearly all cervical cancers (CESC), a subset of other anogenital squamous cancers, and increasing rates of head and neck squamous cell carcinomas (HNSC), with each cancer type having heterogenous outcomes due to a general lack of personalized care. Large scale genomic analyses have catalogued the somatic alterations occurring frequently among squamous tumor types including HNSC and CESC, but few studies have incorporated a thorough analysis of HPV genomics. High-risk HPVs are double-stranded DNA (dsDNA) viruses capable of integrating their genomes into host chromosomes, a phenomenon known to promote HPV-associated cancer formation. HPV …

Ftsk Regulates The Assembly Of The Division Machinery In The Ftsz-Less Chlamydia Trachomatis, Mckenna Katherine Harpring

Theses and Dissertations (ETD)

In evolving to obligate intracellular dependence, Chlamydia trachomatis serovar L2 (Ct), has eliminated several gene products essential for cell division in most other bacteria, including FtsZ, the central coordinator of divisome assembly. In the absence of FtsZ, we show that divisome assembly in Ct is initiated by FtsK, a chromosomal translocase. Chlamydial FtsK forms discrete foci at the septum and at the base of the progenitor mother cell, and our data indicate that FtsK foci at the base of the mother cell mark the location of nascent divisome complexes that form at the site where a daughter cell will emerge …

Interplay Of Antibody Responses To Closely Related Viruses And Autoimmunity, Chun-Yang Lin

Theses and Dissertations (ETD)

Antibodies produced by B cells are crucial for eliminating infectious pathogens and preventing secondary infection. However, antibodies may also bind to self-antigens and contribute to autoimmune disease. While pathogen infections have been associated with development of autoimmune diseases, the precise contributions of viral infections to autoimmunity remain elusive. The presence of autoreactive antibodies is associated with an increased risk of developing autoimmune disease. Thus, analyzing the impact of viral infection and vaccination on the development of autoreactive antibodies will provide essential insight into mechanisms that contribute to autoimmune disease.

Examining How Non-Antifungal Medications Impact Host-Fungal Interactions, Parker Ryan Reitler

Theses and Dissertations (ETD)

Invasive fungal infections (IFIs) are estimated to kill 1.5 million people each year with mortality rates remaining high (around 30-70%), despite the availability of three major classes of antifungal drugs. Furthermore, millions more suffer debilitating infections of the mucosal membranes or destructive subcutaneous mycoses. One of the most common IFIs is invasive candidiasis, mostly commonly caused by Candida albicans infections, with mortality rates of approximately 30%. In addition, the population of susceptible individuals and the incidences of both mucosal and systemic mycoses continue to rise due to the widespread use of broad-spectrum antibacterial agents, cancer chemotherapies, and the immune suppressive …

Genotypes Of Snps Of Key Genes Regulate Susceptibility And Drug Sensitivity To Neovascular Amd, Jinglin Cui

Theses and Dissertations (ETD)

Age-related macular degeneration (AMD), particularly its neovascular form, stands as a leading cause of blindness globally, with its prevalence in our country on a steady rise. This underscores the critical impact of neovascular AMD (nAMD) management on patient quality of life and societal burden. Current optimal treatments hinge on anti-vascular endothelial growth factor (anti-VEGF) therapies, though their efficacy varies across different drugs and individuals, highlighting the importance of precise drug selection in clinical outcomes. Research suggests that factors such as baseline vision, age, disease duration, lesion size, central retina thickness, neovascularization type, and demographic differences influence nAMD prognosis. In addition, …

The Validity And Reliability Of Ultrasound As A Tool For Assessing Skeletal Muscle Characteristics In The Pediatric Population, Elizabeth Seewer

Theses and Dissertations (ETD)

Annually, around 5 million people in the U.S. are admitted to Intensive Care Units (ICU) due to critical conditions, with pediatric patients comprising 21% of these admissions. Approximately 40% of pediatric ICU (PICU) patients require mechanical ventilation and extended stays, and about 6% result in death. Survivors often face long-term disabilities, including loss of skeletal muscle mass (SMM), a risk factor for morbidity and mortality. Abdominal computed tomography (CT) scans, often performed during PICU admissions, can assess muscle mass but pose risks of increased cost and radiation exposure. While CT and Magnetic Resonance Imaging (MRI) are gold standards for muscle …

Anatomical And Physiological Characterization Of Striatal Activation Of The Cerebral Cortex, Yuhan Wang

Theses and Dissertations (ETD)

Purpose. The striatum receives excitatory glutamatergic input from nearly all parts of the cerebral cortex, and its output is delivered by direct pathway medium spiny neurons (dMSNs) expressing D1 type dopamine (DA) receptors (D1Rs) and indirect pathway MSNs (iMSNs) expressing D2 DA receptors (D2Rs). Loss of DA results in the imbalance between the activities of dMSNs and iMSNs in Parkinson’s disease (PD), leading to ab-normal interactions between the cerebral cortex and striatum. Thus, understanding the inter-actions between the cortex and striatum is important. The monosynaptic corticostriatal cir-cuit has been extensively studied. In contrast, due to the poly-synaptic nature of the …

Molecular Determinants Of Trp Channel Gating, Briar J. Bell

Theses and Dissertations (ETD)

Transient Receptor Potential (TRP) ion channels are a family of proteins that contribute to a myriad of physiological functions. They have been extensively studied since their discovery 35 years ago; however, there are still many questions regarding the mechanisms by which they function. This family of proteins is characterized by a generally shared structure: an intracellular N terminus featuring ankyrin repeats, six transmembrane helices including the pore domain, a re-entrant loop and TRP helix, and an intracellular C terminus with varying structure. Each of these regions has been implicated in the regular function of TRPs, while mutations that alter trafficking …

Improving Estimation Of Coronary Artery Disease Risk Using Haptoglobin Genotyping, Emily Kate Mewborn

Theses and Dissertations (ETD)

Atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of death worldwide. While several risk factors contributing to disease progression are well-known, pitfalls and limitations exist for estimating if or when an individual will develop the disease. Coronary artery disease (CAD), a subtype of ASCVD, causes myocardial infarction, contributing to significant morbidity and mortality. Current ASCVD risk estimator calculators lack comprehensiveness and do not include genetic or social determinants of health information, which are known to affect ASCVD risk.

Haptoglobin (Hp) genotype also influences CAD risk. Hp is a protein that binds free hemoglobin released from physiologic or pathologic …

Development Of Novel, Brain Permeable, Mpges-1 Inhibitors For Inflammatory Conditions, Madison Sluter

Theses and Dissertations (ETD)

Prostaglandin E2 (PGE2) is a potent proinflammatory lipid signaling molecule produced downstream of the cyclooxygenase (COX) cascade. The COX pathway has long been implicated for its role in inflammation, with drugs like aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) non-selectively targeting the upstream COX enzymes to suppress inflammation. However, despite displaying potent anti-inflammatory effects it has been demonstrated that when taken chronically, NSAIDs can cause gastrointestinal bleeding. COX-2 selective inhibitors (COXIBs) were then developed to combat the gastrointestinal bleeding induced by nonselective NSAIDs by specifically inhibiting the COX enzyme most infamous for its role in inflammation. Yet, soon after entering …

Studies On The Leukocyte-Associated Ig-Like Inhibitory Receptor-1 Signaling Pathway In T Lymphocytes, Chidi Zacheaus

Theses and Dissertations (ETD)

Inflammation is a natural process in which the immune system concertedly responds to pathogens and abnormal cell growth to protect the host. For an efficient/effective immune response that circumvents tissue atrophy, a delicate balance between stimulatory and inhibitory mechanisms is essential for the proper functioning of the immune system. Immuno-receptor Tyrosine-based Inhibitory Motif (ITIM)-bearing receptors in immune cells, including T lymphocytes, play a major role in preventing autoimmune responses. Leukocyte-associated Ig-like Inhibitory Receptor 1 (LAIR-1) is one of ITIM-bearing receptors. The mechanism by which LAIR-1 attenuates T-cell response has yet to be completely understood. In this study, I investigated a …

The Interaction Between Host G3bp And Viral Nucleocapsid Protein Regulates Sars-Cov-2 Replication, Zemin Yang

Theses and Dissertations (ETD)

G3BP1/2 are RNA-binding proteins that promote condensation to form stress granules in response to various cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP-N interaction in the context of viral infection have remained unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively disrupt their interaction. We found that mutation of N-F17 led to selective loss of interaction with G3BP1 and consequent failure of …

Tcf4 Is A Key Mediator Of Cell Identity And Oncogenesis In Neuroblastoma, Nour Aljouda

Theses and Dissertations (ETD)

Neuroblastomas (NB) are embryonal childhood tumors that derive from the multipotent neural crest cells (NCCs) of the peripheral nervous system. NB accounts for more than 15% of all childhood cancer-related deaths. Despite the most intensive multimodal therapy, more than 50% of patients with high-risk NB relapse with often fatal, resistant disease. Novel therapies are desperately needed to improve cure rates. Previous studies proposed that the deregulation of normal neural crest developmental programs contributes to NB oncogenesis by retaining the highly migratory and proliferative traits of NCCs. Thus, activation or repression of neural crest developmental pathways have been implicated in NB …

Cytochrome P450 1b1 And 12/15 Lipoxygenase Interaction In Paraventricular Nucleus In Angiotensin Ii-Induced Hypertension In Females, Shubha Ranjan Dutta

Theses and Dissertations (ETD)

Background: Angiotensin (Ang) II releases arachidonic acid (AA) from tissue phospholipids that is metabolized by 12/15-lipoxygenase (ALOX15) generating 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) which have been implicated in cardiovascular and renal diseases. This study was conducted to investigate a) the contribution of ALOX15 to Ang II-induced hypertension and associated pathogenesis in female mice, and b) the interaction between the cytochrome P450 (CYP)1B1-generated metabolite of 17β-estradiol (E2) (2-methoxyestradiol, 2-ME) and ALOX15 in the paraventricular nucleus (PVN) as a mechanism that protects against Ang II-induced hypertension and its associated pathogenesis in female mice. Methods: Experiments were conducted in intact and ovariectomized (OVX) …

The Effects Of Exosomal Derived Tsg-6 On Microglia Activation, Jonathan A. Martinez, Rajashekhar Gangaraju Md

Longitudinal Scholar's Project

Following a traumatic brain injury, microglia become overactive for long periods and display pathologic behavior. We have shown that concentrated conditioned media from adipose tissue-derived mesenchymal stem cells (MSC-CCM) can suppress microglial activation. In this pilot study, we evaluated the efficacy of exosomes containing TNF-stimulated gene 6 (TSG6) derived from MSC-CCM on decreasing microglial activation in vitro via phagocytic activity and pro-inflammatory microglial gene expression.

A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang

Theses and Dissertations (ETD)

Introduction. Ischemic heart disease (IHD) is a major concern of human health issue. The structural repair and functional recovery of injured hearts is a major challenge in the clinical setting. Preclinical studies over last 10 years have demonstrated the potential of using stem cells to treat IHD, but the efficacy of this therapy is jeopardized by uncontrollable migration and low survival of the injected stem cells. An approach based on tissue engineering enabling target-specific stem cell delivery such as cardiac patches has emerged as an alternative solution for stem cell therapy for IHD. It employs scaffold materials to engulf various …