Medical Sciences Commons^™

Cross-Contamination Of Crispr Guides And Other Unrelated Nucleotide Sequences Among Commercial Oligonucleotides, Hiroshi Arakawa, Hiromi Miura, Rolen M. Quadros, Masato Ohtsuka, Channabasavaiah B. Gurumurthy

Journal Articles: Genetics, Cell Biology & Anatomy

Custom oligonucleotides (oligos) are widely used reagents in biomedical research. Some common applications of oligos include polymerase chain reaction (PCR), sequencing, hybridization, microarray, and library construction. The reliability of oligos in such applications depends on their purity and specificity. Here, we report that commercially available oligos are frequently contaminated with nonspecific sequences (i.e. other unrelated oligonucleotides). Most of the oligos that we designed to amplify clustered regularly interspersed palindromic repeats (CRISPR) guide sequences contained nonspecific CRISPR guides. These contaminants were detected in research-grade oligos procured from eight commercial oligo-suppliers located in three different geographic regions of the world. Deep sequencing …

Granulocytic Myeloid-Derived Suppressor Cell Activity During Biofilm Infection Is Regulated By A Glycolysis/Hif1a Axis, Christopher M. Horn, Prabhakar Arumugam, Zachary Van Roy, Cortney E. Heim, Rachel W. Fallet, Blake P. Bertrand, Dhananjay Shinde, Vinai Chittezham Thomas, Svetlana Romanova, Tatiana K. Bronich, Curtis Hartman, Kevin Garvin, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI). A primary contributor to infection chronicity is an expansion of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are critical for orchestrating the antiinflammatory biofilm milieu. Single-cell sequencing and bioinformatic metabolic algorithms were used to explore the link between G-MDSC metabolism and S. aureus PJI outcome. Glycolysis and the hypoxia response through HIF1a were significantly enriched in G-MDSCs. Interfering with both pathways in vivo, using a 2-deoxyglucose nanopreparation and granulocyte-targeted Hif1a conditional KO mice, respectively, attenuated G-MDSC-mediated immunosuppression and reduced bacterial burden in a mouse model of S. aureus PJI. …

Innate And Adaptive Immune System Consequences Of Post-Traumatic Stress Disorder, Tatlock H. Lauten, Tamara Natour, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopathologies, which makes diagnosis highly subjective. Moreover, therapies for mental health disorders are aimed specifically at attenuating behavioral manifestations, which overlooks the pathophysiological indices of the disease. This is highly evident in posttraumatic stress disorder (PTSD) where inflammation and immune system perturbations are becoming increasingly described. Further, patients with PTSD possess significantly elevated risks of developing comorbid inflammatory diseases such as autoimmune and cardiovascular diseases, which are likely linked …

Activation Of Renal Epithelial Na+ Channels (Enac) In Infants With Congenital Heart Disease, Laura Ortmann, Shyam Sundar Nandi, Yulong Li, Hong Zheng, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

INTRODUCTION: This study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na

METHODS: Urine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6-8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls. The urine was tested for four proteases and whole-cell patch-clamp testing was conducted in renal collecting duct M-1 cells to test whether patient urine increased Na

RESULTS: Heavy chain of plasminogen, furin, and prostasin were significantly higher in cardiac patients prior to …

Investigation Into Cardiac Myhc-Α 334-352-Specific Tcr Transgenic Mice Reveals A Role For Cytotoxic Cd4 T Cells In The Development Of Cardiac Autoimmunity, Meghna Sur, Mahima T. Rasquinha, Kiruthiga Mone, Chandirasegaran Massilamany, Ninaad Lasrado, Channabasavaiah B. Gurumurthy, Raymond A Sobel, Jay Reddy

Journal Articles: Genetics, Cell Biology & Anatomy

Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4⁺ and CD8⁺ T cells, but defining antigen specificity in disease pathogenesis is challenging. To address this issue, we generated T cell receptor (TCR) transgenic (Tg) C57BL/6J mice specific to cardiac myosin heavy chain (Myhc)-α 334-352 and found that Myhc-α-specific TCRs were expressed in both CD4⁺ and CD8⁺ T cells. To investigate if the phenotype is more pronounced in a myocarditis-susceptible genetic background, we backcrossed with A/J mice. At …

International Consensus On Sleep Problems In Pediatric Palliative Care: Paving The Way, Anna Mercante, Judith Owens, Oliviero Bruni, Magda L. Nunes, Paul Gringras, Shirley Xin Li, Simonetta Papa, Ulrika Kreicbergs, Joanne Wolfe, Boris Zernikow, Ana Lacerda, Franca Benini, Pediatric Sleep And Palliative Care Group

Journal Articles: Munroe-Meyer Institute

OBJECTIVE: Sleep problems constitute a common and heterogeneous complaint in pediatric palliative care (PPC), where they often contribute to disease morbidity and cause additional distress to children and adolescents and their families already facing the burden of life-threatening and life-limiting conditions. Despite the significant impact of sleep problems, clinical evidence is lacking. The application of general pediatric sleep recommendations appears insufficient to address the unique challenges of the PPC dimension in terms of disease variability, duration, comorbidities, complexity of needs, and particular features of sleep problems related to hospice care. Therefore, we initiated an international project aimed at establishing a …

Metabolism Shapes Immune Responses To Staphylococcus Aureus., Prabhakar Arumugam, Tammy Kielian

Journal Articles: Pathology and Microbiology

BACKGROUND: Staphylococcus aureus (S. aureus) is a common cause of hospital- and community-acquired infections that can result in various clinical manifestations ranging from mild to severe disease. The bacterium utilizes different combinations of virulence factors and biofilm formation to establish a successful infection, and the emergence of methicillin- and vancomycin-resistant strains introduces additional challenges for infection management and treatment.

SUMMARY: Metabolic programming of immune cells regulates the balance of energy requirements for activation and dictates pro- versus anti-inflammatory function. Recent investigations into metabolic adaptations of leukocytes and S. aureus during infection indicate that metabolic crosstalk plays a crucial role in …

Elucidating Granulocytic Myeloid-Derived Suppressor Cell Heterogeneity During Staphylococcus Aureus Biofilm Infection, Blake P. Bertrand, Cortney E. Heim, Scott A. Koepsell, Tammy Kielian

Journal Articles: Pathology and Microbiology

Myeloid-derived suppressor cells (MDSCs) are pathologically activated immature myeloid cells with immunosuppressive activity that expand during chronic inflammation, such as cancer and prosthetic joint infection (PJI). Myeloid-derived suppressor cells can be broadly separated into 2 populations based on surface marker expression and function: monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic myeloid-derived suppressor cells (G-MDSCs). Granulocytic myeloid-derived suppressor cells are the most abundant leukocyte infiltrate during PJI; however, how this population is maintained in vivo and cellular heterogeneity is currently unknown. In this study, we identified a previously unknown population of Ly6G+Ly6C+F4/80+MHCII+ MDSCs during PJI that displayed immunosuppressive properties ex vivo. …

C1q Is Elevated During Chronic Staphylococcus Epidermidis Central Nervous System Catheter Infection, Matthew K. Beaver, Lara Bergdolt, Anna Dunaevsky, Tammy Kielian, Gwenn Skar

Journal Articles: Pathology and Microbiology

INTRODUCTION: Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation.

METHODS: We examined complement activation throughout

RESULTS: We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and …

Antimicrobial Activity Of Gallium(Iii) Compounds: Pathogen-Dependent Targeting Of Multiple Iron/Heme-Dependent Biological Processes, Seoung-Ryoung Choi, Mohammed A. Hassan, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth …

Aconitate Decarboxylase 1 Mediates The Acute Airway Inflammatory Response To Environmental Exposures, Aaron Schwab, Amy J. Nelson, Angela Gleason, Oliver Schanze, Todd A. Wyatt, Dhananjay Shinde, Peng Xiao, Vinai Chittezham Thomas, Chittibabu Guda, Kristina L. Bailey, Tammy Kielian, Geoffrey M. Thiele, Jill A. Poole

Journal Articles: Pathology and Microbiology

Background: Environmental lipopolysaccharide (LPS) and microbial component-enriched organic dusts cause significant lung disease. These environmental exposures induce the recruitment and activation of distinct lung monocyte/macrophage subpopulations involved in disease pathogenesis. Aconitate decarboxylase 1 (Acod1) was one of the most upregulated genes following LPS (vs. saline)exposure of murine whole lungs with transcriptomic profiling of sorted lung monocyte/macrophage subpopulations also highlighting its significance. Given monocyte/macrophage activation can be tightly linked to metabolism, the objective of these studies was to determine the role of the immunometabolic regulator ACOD1 inenvironmentalexposure-induced lung inflammation.

Methods: Wild-type (WT) mice were intratracheally (i.t.) instilled with 10 …

Bacterial Single-Cell Rna Sequencing Captures Biofilm Transcriptional Heterogeneity And Differential Responses To Immune Pressure, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilm formation is an important mechanism of survival and persistence for many bacterial pathogens. These multicellular communities contain subpopulations of cells that display metabolic and transcriptional diversity along with recalcitrance to antibiotics and host immune defenses. Here, we present an optimized bacterial single-cell RNA sequencing method, BaSSSh-seq, to study Staphylococcus aureus diversity during biofilm growth and transcriptional adaptations following immune cell exposure. BaSSSh-seq captures extensive transcriptional heterogeneity during biofilm compared to planktonic growth. We quantify and visualize transcriptional regulatory networks across heterogeneous biofilm subpopulations and identify gene sets that are associated with a trajectory from planktonic to biofilm growth. BaSSSh-seq …

Metabolic Diversity Of Human Macrophages: Potential Influence On Staphylococcus Aureus Intracellular Survival, Blake P. Bertrand, Dhananjay Shinde, Vinai C. Thomas, Marvin Whiteley, Carolyn B. Ibberson, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of medical device-associated biofilm infections. This is influenced by the ability of S. aureus biofilm to evade the host immune response, which is partially driven by the anti-inflammatory cytokine interleukin-10 (IL-10). Here, we show that treatment of human monocyte-derived macrophages (HMDMs) with IL-10 enhanced biofilm formation, suggesting that macrophage anti-inflammatory programming likely plays an important role during the transition from planktonic to biofilm growth. To identify S. aureus genes that were important for intracellular survival in HMDMs and how this was affected by IL-10, transposon sequencing was performed. The size of the S. aureus …

Dual Gallium Drug Treatment Against Carbapenem-Resistant Klebsiella Pneumoniae: Efficacy And Potential Mechanism(S) Of Action And Resistance, Zachary Scott, Seoung-Ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Klebsiella pneumoniae (KLP) is a Gram-negative pathogen that can be highly antibiotic-resistant. Our group has worked with gallium-based compounds as a means of treating bacterial infections. Here the possible mechanism is investigated for dual therapy comprised of gallium nitrate (Ga(NO₃)₃) and gallium protoporphyrin (GaPP) on KLP. It is found that in vitro the combination of Ga(NO₃)₃ and GaPP is synergistic against KLP. The in vivo efficacy is of the dual therapy is additionally tested by treating pulmonary KLP infections in mice. Much greater effectiveness are observed in bacterial clearance and survival of mice …

Tetracycline And Oxacillin Act Synergistically On Biofilms And Display Increased Efficacy In Vivo Against Staphylococcus Aureus, Amy K. Tooke, Rebecca E. Hodges, Josie F. Pyrah, Kenneth W. Bayles, Stephen A. Renshaw, Simon J. Foster

Journal Articles: Pathology and Microbiology

Oxacillin (bactericidal) and tetracycline (bacteriostatic) are clinically relevant antibiotics that are routinely prescribed to treat Staphylococcus aureus infections but not conventionally used in combination. There is an urgent need for treatment regimens that can act upon biofilms during infection, associated with chronic infections on indwelling devices, as well as acute planktonic (systemic) infection. Here we show that in an in vitro model oxacillin and tetracycline act synergistically against S. aureus UAMS-1 biofilms, reducing the concentration of both antibiotics necessary to eradicate an established biofilm. Using an in vivo zebrafish larval infection model with S. aureus NewHG, they display improved bacterial …

Potential Prognostic Determinants For Fet::Creb Fusion-Positive Intracranial Mesenchymal Tumor, Frank M. Mezzacappa, Frankie K. Smith, Weiwei Zhang, Andrew Gard, Fatmagul Kusku Cabuk, Ignancio Gonzalez-Gomez, Hector L. Monforte, Jiancong Liang, Omkar Singh, Martha M. Quezado, Kenneth D. Aldape, Murat Gokden, Julia A. Bridge, Jie Chen

Journal Articles: Pathology and Microbiology

Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1::CREM fusion and two featuring an EWSR1::ATF1 fusion. Uniform manifold approximation and projection of DNA methylation array data placed two cases to the methylation class "IMT, subclass B", one to "meningioma-benign" and one to "meningioma-intermediate". A literature review identified 74 cases of IMTs (current five cases included) with a median age of 23 years (range 4-79 years) and …

Chemoreflex Sensitization Occurs In Both Male And Female Rats During Recovery From Acute Lung Injury, Kajal Kamra, Irving H. Zucker, Harold D. Schultz, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

Introduction: Sex-specific patterns in respiratory conditions, such as asthma, COPD, cystic fibrosis, obstructive sleep apnea, and idiopathic pulmonary fibrosis, have been previously documented. Animal models of acute lung injury (ALI) have offered insights into sex differences, with male mice exhibiting distinct lung edema and vascular leakage compared to female mice. Our lab has provided evidence that the chemoreflex is sensitized in male rats during the recovery from bleomycin-induced ALI, but whether sex-based chemoreflex changes occur post-ALI is not known. To bridge this gap, the current study employed the bleomycin-induced ALI animal model to investigate sex-based differences in chemoreflex activation during …

Targeted Insertion Of Conditional Expression Cassettes Into The Mouse Genome Using The Modified I-Pitt, Hiromi Miura, Ayaka Nakamura, Aki Kurosaki, Ai Kotani, Masaru Motojima, Keiko Tanaka, Shigeru Kakuta, Sanae Ogiwara, Yuhsuke Ohmi, Hirotaka Komaba, Samantha L. P. Schilit, Cynthia C. Morton, Channabasavaiah B. Gurumurthy, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Transgenic (Tg) mice are widely used in biomedical research, and they are typically generated by injecting transgenic DNA cassettes into pronuclei of one-cell stage zygotes. Such animals often show unreliable expression of the transgenic DNA, one of the major reasons for which is random insertion of the transgenes. We previously developed a method called "pronuclear injection-based targeted transgenesis" (PITT), in which DNA constructs are directed to insert at pre-designated genomic loci. PITT was achieved by pre-installing so called landing pad sequences (such as heterotypic LoxP sites or attP sites) to create seed mice and then injecting Cre recombinase or …

Single-Cell Profiling Reveals A Conserved Role For Hypoxia-Inducible Factor Signaling During Human Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Lee E. Korshoj, Joseph P. Menousek, Cortney E. Heim, Rachel W. Fallet, James Campbell, Carol Reynolds Geary, Bo Liu, Santhi Gorantla, Larisa Y Poluektova, Bin Duan, Walter S. Campbell, William Thorell, Tammy Kielian

Journal Articles: Pathology and Microbiology

Neurosurgeries complicated by infection are associated with prolonged treatment and significant morbidity. Craniotomy is a common neurosurgical procedure; however, the cellular and molecular signatures associated with craniotomy infection in human subjects are unknown. A retrospective study of over 2,500 craniotomies reveals diverse patient demographics, pathogen identity, and surgical landscapes associated with infection. Leukocyte profiling in patient tissues from craniotomy infection characterizes a predominance of granulocytic myeloid-derived suppressor cells that may arise from transmigrated blood neutrophils, based on single-cell RNA sequencing (scRNA-seq) trajectory analysis. Single-cell transcriptomic analysis identifies metabolic shifts in tissue leukocytes, including a conserved hypoxia-inducible factor (HIF) signature. The …

Understanding The Function Of Pax5 In Development Of Docetaxel-Resistant Neuroendocrine-Like Prostate Cancers, Sreyashi Bhattacharya, Hannah Harris, Ridwan Islam, Sanika Bodas, Navatha S. Polavaram, Juhi Mishra, Dipanwita Das, Parthasarathy Seshacharyulu, Achyuth Kalluchi, Anirban Pal, Manish Kohli, Subodh M. Lele, Michael Muders, Surinder K. Batra, Paramita M. Ghosh, Kaustubh Datta, M. Jordan Rowley, Samikshan Dutta

Journal Articles: Biochemistry & Molecular Biology

Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small-cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential. During t-NEPC transformation, adenocarcinomas lose their luminal features and adopt neuro-basal characteristics. Whether the adaptive neuronal characteristics of t-NEPC are responsible for such taxane resistance remains unknown. Pathway analysis from patient gene-expression …

The Expression Of The Claudin Family Of Proteins In Colorectal Cancer, Kristin E. Cox, Shanglei Liu, Robert M. Hoffman, Surinder K. Batra, Punita Dhawan, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

Claudins (CLDN1-CLDN24) are a family of tight junction proteins whose dysregulation has been implicated in tumorigeneses of many cancer types. In colorectal cancer (CRC), CLDN1, CLDN2, CLDN4, and CLDN18 have been shown to either be upregulated or aberrantly expressed. In the normal colon, CLDN1 and CLDN3-7 are expressed. Although a few claudins, such as CLDN6 and CLDN7, are expressed in CRC their levels are reduced compared to the normal colon. The present review outlines the expression profiles of claudin proteins in CRC and those that are potential biomarkers for prognostication.

Citrullinated And Malondialdehyde-Acetaldehyde Modified Proteins Promote Cellular Inflammatory And Fibrotic Responses Associated With Rheumatoid Arthritis, Nozima Aripova

Theses & Dissertations

Rheumatoid arthritis (RA) is a systemic, autoimmune disease primarily characterized by perpetual synovial inflammation that results in synovial tissue proliferation and fibrosis (pannus). Although joint involvement is the predominant manifestation of RA, extra-articular features, such as interstitial lung disease (ILD), contribute significantly to the elevated mortality associated with the condition. Post-translational modifications play a significant role in RA and RA-ILD pathogenesis. Circulating anti-citrullinated protein antibodies (ACPAs) are a highly diagnostic tool implicating a potential role for citrullinated antigens in RA and RA-ILD.

Recently, antibodies to malondialdehyde acetaldehyde adducts (MAA) have been markedly elevated in patients with RA and RA-ILD. MAA …

Identification Of Immune Biomarkers In Thyroid Cancer, Anupam Kotwal

Theses & Dissertations

Thyroid cancer is the most common endocrine malignancy, estimated to be the second most common cancer in women by 2030. The frequency of differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, is higher in patients with autoimmune thyroid disease but the influence of the immune milieu on thyroid carcinogenesis remains unclear. To address this gap in knowledge, we performed clinical and translational experiments to identify immune biomarkers for the occurrence and prognosis of DTC. Multiparameter flow cytometry of peripheral blood from 32 adults found advanced thyroid cancer either at presentation or during the disease-course to be associated …

The Co-Oncogenic Function Of Ecdysoneless Protein With Erbb2 In Mammary Epithelial Cells, Benjamin B. Kennedy

Theses & Dissertations

The Ecdysoneless (ECD) protein is highly evolutionarily conserved and ubiquitously expressed across human tissues. ECD has established roles in cell cycle regulation, embryogenesis, cell survival, and RNA biogenesis. ECD mRNA and protein are overexpressed in breast cancer, and its overexpression correlates with poor patient survival, especially in ErbB2/HER2-positive breast cancer. This thesis work investigates the co-oncogenic role of ECD in ErbB2-driven oncogenesis using immortalized mammary epithelial cells. Here, we show that ECD and ErbB2 overexpression in immortalized human mammary epithelial cells increases cancer traits, such as invasion, migration, and anchorage independent growth. Significantly, ECD+ErbB2 co-overexpression further enhanced all oncogenic traits. …

A Qualitative Analysis Of Candida Auris Laboratory Surveillance In Nebraska, Lissa M. Young

Capstone Experience: Master of Public Health

Objectives: Candida auris is an emerging pathogenic yeast that was first identified in Japan in 2009 and detected in the United States in 2015. As of 2020, C. auris has been reported in cases throughout 41 countries, including the United States. The ability of this species of yeast to spread rapidly and survive for long periods of time on surfaces, the high mortality rate of those infected, and its multidrug resistant phenotype, have rendered it a urgent public health threat (the highest threat level) by the United States Centers for Disease Control and Prevention beginning in 2019 (CDC, 2019). Since …

Lessons Learned Creating Microbiology Laboratory Demonstration Videos, Marnie Imhoff, Linsey Donner

Innovations in Health Sciences Education Journal

Microbiology laboratory classes are designed to allow students to apply knowledge gained during lectures and become proficient in laboratory skills. Students are introduced to procedures for working with and identifying microorganisms. Instructors must prepare students to perform and interpret the necessary testing procedures to be successful. Laboratory demonstration videos provide students with a first-person, unobstructed demonstration on how to perform laboratory techniques. The videos can be used as a visual learning tool to supplement courses with an in-person laboratory session or as a component in online learning. This article describes the creation of instructional microbiology laboratory demonstration videos.

Effect Of Computerized Cognitive Training In Persons With Multiple Sclerosis, Sam Jack

Theses & Dissertations

Between one million and 1.75 million persons with multiple sclerosis (PwMS) worldwide are estimated to suffer from cognitive impairment. Unfortunately, there is currently no consensus on the best treatment for cognitive impairment in PwMS. Finding non-pharmacological interventions to mitigate cognitive decline is essential to ensure that quality of life for PwMS matches our ability to treat and mitigate their physical symptoms of MS. Computerized cognitive training has emerged as a potential option for PwMS suffering from cognitive impairment. The objective of this study was to determine the effectiveness of computerized cognitive training with BrainHQ on changes in cognitive impairment for …

Development Of Combination Therapy Strategies To Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors, Nicholas Mullen

Theses & Dissertations

Cancer cells require supraphysiologic levels of nucleotide triphosphates to fuel their malignant behaviors, including uncontrolled proliferation, immune evasion, metastasis, and therapy resistance. This requirement is met by hyperactive flux through the de novo pyrimidine and de novo purine pathways. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine pathway that can be targeted by FDA approved and experimental drug compounds. A robust body of preclinical evidence, encompassing hundreds of independent studies over several decades, demonstrates impressive activity of DHODH inhibitors in animal models of cancer. Paradoxically, however, all clinical trials to date have failed to demonstrate efficacy …

Center Based Cardiac Rehabilitation Outcomes Associated With Covid-19 Pandemic: A Retrospective Comparative Cohort Study, Haley Williams, Kayla Woodworth

Doctor of Nursing Practice Projects: College of Nursing

Background: Traditional cardiac rehabilitation (CR) is a multidisciplinary, multifaceted program for cardiac patients. Throughout the Covid-19 pandemic, health care, including center-based CR (CBCR) programs, were closed to in-person sessions. Even with the return to CBCR participation, patient outcomes may have been affected by this disruption in care. The goal of this study was to determine if CR participation outcomes differed before and after CBCR program closure due to Covid-19.

Methods: A retrospective comparative cohort design was used to examine CR participant outcome data before and after the Covid-19 pandemic. Convenience sampling of CR participants at a large, urban …

Evaluating The Impact Of Routine Enteral Iron Fortification On Gastrointestinal Dysbiosis In Premature Infants, Matthew Van Ormer

Theses & Dissertations

The gastrointestinal microbiome in preterm infants bears significant influence on optimal outcomes – dysbiosis is shown to substantially increase the risk of the life-threatening necrotizing enterocolitis, whereas optimal microbiome composition improves nutrient digestion and immune function. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurological development. However, excess colonic iron exhibits potent oxidation capacity and alters the competitive environment of microbes – potentially facilitating the proliferation of pathological bacterial strains in the gut. Of note, breastfed preterm infants routinely receive iron fortification starting at 14 days of life and are …