Diseases Commons^™

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Implementing A Standardized Protocol For Early Detection Of Undiagnosed Hypertension Patients, Jenscena Hansen, Chris Bell

Doctor of Nursing Practice Projects: College of Nursing

Introduction: Hypertension is a preventable disease that frequently goes unrecognized and undertreated. Early diagnosis can prevent further comorbidities such as heart disease, stroke, and chronic kidney disease. Implementation of this protocol aims to decrease the number of patients with undiagnosed hypertension and increase the identification of patients with elevated blood pressure who did not have a pre-existing diagnosis of hypertension. The goal of implementing a standardized protocol would help eliminate the number of patients who go undiagnosed.

Methods: This quality improvement design had clinical staff flag patients with elevated blood pressure. Identified patients without a diagnosis of hypertension were educated …

Identifying Barriers To Healthcare Access And Utilization Experienced By Lgbtq+ Adults With Chronic Diseases Through The Lens Of The Social Ecological Model, Devin Mottier

Capstone Experience: Master of Public Health

The purpose of this literature review is to comprehensively examine and synthesize existing research on present barriers to health access and utilization that contribute to the disparities in chronic disease prevalence within the adult LGBTQ+ population. In the context of this review, the social-ecological model (SEM) was used to describe the nuanced and multifaceted nature of healthcare access and utilization. This literature review was based upon the following question: ‘Using the social-ecological model, what are the barriers to health access and utilization that contribute to high rates of chronic disease in LGBTQ+ adults?’ Outcome measures of interest included the following …

One Year Follow Up Of A Cross-Sectional Study Of Hookworm Infection And Response To Deworming In Beposo, Ghana, Taylor Clarkson

Capstone Experience: Master of Public Health

Hookworms are soil-transmitted helminths that infect over 500 million people worldwide, primarily those in low-income countries. Infection with hookworm can cause anemia, malnutrition, and stunted physical and cognitive development. Deworming campaigns have attempted to combat hookworm infections in endemic areas for decades. However, there is growing variability in the effectiveness of deworming drugs, and post-treatment reinfections are abundant. There are significant gaps in our understanding of critical host-parasite factors that mediate hookworm infection, reinfection, and response to deworming treatment in endemic communities. A five-year prospective study was undertaken to better understand drivers of hookworm infection in rural Ghana and thus …

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …

Targeting Transitioning Lung Monocytes/Macrophages As Treatment Strategies In Lung Disease Related To Environmental Exposures, Aaron Schwab, Todd A. Wyatt, Grace Moravec, Geoffrey M. Thiele, Amy J. Nelson, Angela Gleason, Oliver Schanze, Michael J. Duryee, Debra J. Romberger, Ted R. Mikuls, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Background: Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited,transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear.

Methods: CCR2 RFP⁺ mice were intratracheally instilled with high concentration ODE (25%), LPS (10 μg), or gram-positive peptidoglycan (PGN, 100 μg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure.Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. …

Lung-Delivered Il-10 Therapy Elicits Beneficial Effects Via Immune Modulation In Organic Dust Exposure-Induced Lung Inflammation, Aaron D. Schwab, Todd A. Wyatt, Amy J. Nelson, Angela Gleason, Rohit Gaurav, Debra J. Romberger, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Efficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 μg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 …

Polygenic And Transcriptional Risk Scores Identify Chronic Obstructive Pulmonary Disease Subtypes In The Copdgene And Eclipse Cohort Studies, Matthew Moll, Julian Hecker, John Platig, Jingzhou Zhang, Auyon J. Ghosh, Katherine A. Pratte, Rui-Sheng Wang, Davin Hill, Iain R. Konigsberg, Joe W. Chiles, Craig P. Hersh, Peter J. Castaldi, Kimberly Glass, Jennifer G. Dy, Don D. Sin, Ruth Tal-Singer, Majd Mouded, Stephen I. Rennard, Gary P. Anderson, Gregory L. Kinney, Russell P. Bowler, Jeffrey L. Curtis, Merry-Lynn Mcdonald, Edwin K. Silverman, Brian D. Hobbs, Michael H. Cho

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

METHODS: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing …

Massive Upper Gi Bleeding From Duodenal Invasion Of Hepatocellular Carcinoma Successfully Treated With Embolization And Hemospray®, Patrick Twohig, Erin Walsh, Amy Calderon

Graduate Medical Education Research Journal

Direct invasion of hepatocellular carcinoma (HCC) into the duodenum is a unique and life-threatening complication of HCC that has been rarely reported. A 60-year-old male with known HCC and cirrhosis presented with melena. Computed tomography of the abdomen and pelvis showed a 7cm hepatic mass abutting the duodenum. Esophagogastroduodenoscopy demonstrated a large, actively oozing mass in the duodenum treated with Hemospray® followed by transarterial embolization (TAE). Active upper gastrointestinal bleeding due to duodenal invasion of HCC can be successfully treated with Hemospray® Endoscopic Hemostat and TAE.

Prostatic Utricle Presenting As A Midline Scrotal Mass, Kaitlyn E. Schultis, Bryant Van Leeuwen, John Makari

Graduate Medical Education Research Journal

The prostatic utricle is a remnant of the Müllerian duct located within the verumontanum. An enlarged, clinically significant prostatic utricle has classically been associated with hypospadias. Prostatic utricles often present with persistent lower urinary tract symptoms, recurrent infections, and urinary incontinence. We present a prostatic utricle that presented as a scrotal mass concerning for rhabdomyosarcoma in a male with normal external genitalia.

Usp1 Expression Driven By Ews::Fli1 Dually Promotes Ewing Sarcoma Cell Survival By Mitigating The Replication Stress Response And Stabilizing Survivin, Halle Mallard

Theses & Dissertations

Ewing sarcoma (EWS) is a malignant pediatric bone cancer. EWS express a fusion oncogene resulting from the reciprocal translocation of EWSR1 an ETS transcription factor. In most EWS tumors, this occurs with FLI1, creating the EWS::FLI1 fusion oncogene which encodes an aberrant transcription factor. Independent of its transcriptional activity, EWS::FLI1 deregulates other cellular processes driving oncogenesis. For cases with a single, localized tumor, roughly 80% of patients remain event-free after five years. Disease dissemination is a problem – about 25% of patients have metastatic disease at diagnosis. Long-term survival for these patients is less than 40%. Presently, no second line …

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 …

Towards A Mode Of Action For The Anti-Schistosomal Aryl Hydantoins, Thomas Schulze

Theses & Dissertations

Schistosomiasis is a significant human disease caused by the helminth parasite Schistosoma mansoni. Praziquantel remains the only clinically used treatment, yet it is rapidly metabolized and only effective against the adult stage worm infection. Ro 13-3978 (AR02) is a potent antischistosomal compound with activity against multiple S. mansoni life stages; however, it manifests anti-androgenic activity. Additionally, the mechanism of action for worm clearance remains unknown. The structure of Ro 13-3979 was used to generate optimized derivatives, including AR102, that show increased potency towards worms, reduced off-target anti-androgen effects, and extended half-life thereby increasing the feasibility for a single-dose curative treatment. …

To Screen Or Not To Screen: Prostate Cancer In Liver Transplant Candidates, Patrick Twohig, Jared Schober, Timothy Mccashland, Thoetchai Peeraphatdit

Graduate Medical Education Research Journal

Prostate cancer screening is a controversial topic in the general population and is even more contested among liver transplant candidates. Not only should transplant programs be concerned about the risk of false positive screening results but also the competing risks of death and the diagnostic and therapeutic effects of true prostate cancer, which often does not cause significant morbidity or mortality in organ transplant recipients. Our letter highlights a best-practices approach to prostate cancer screening in transplant candidates using available research and consensus guidelines.

Rare Streptococcus Intermedius Central Nervous System Septic Emboli: A Case Report And Review Of Literature, Jonathan Herskovitz, Cristina J. Torres, Bryan Walker, Jasmine R. Marcelin

Graduate Medical Education Research Journal

We report a case of a male in his thirties who presented with rapidly progressive encephalopathy, mediastinal abscess, and multiple ring-enhancing lesions throughout the brain. Extensive evaluation revealed Streptococcus intermedius septic emboli to the brain from dental sources via a right-to-left anatomic shunt. The patient completed an 11-week course of IV antibiotic therapy after which he made a near complete recovery. We provide a comprehensive review of the literature with Streptococcus intermedius CNS septic emboli and source of infection.

Understanding And Quantifying Bioaerosol Fate Within The Aerobiological Pathway: Physical Transport, Environmental Decay, And Mitigation, Sean Kinahan

Theses & Dissertations

The recent COVID-19 pandemic has highlighted the need for better tools to understand and characterize phases of the aerobiological pathway, a model for understanding how infectious bioaerosols are sourced, generated, transported, deposit, and affect human health. This dissertation presents validation of methodologies for studying transport of airborne biological agents and variations on their consequences, especially focusing on their physical and chemical fate. Chapter 1 focuses on a parallel comparison of two methods of aging bioaerosols in real-world outdoor environments with complex sunlight, atmospheric chemistry, and pollutants. Both capture on microfibers and the use of Goldberg rotating drums to keep a …

Investigating Transcriptional Anomalies During Persistence In Chlamydia Trachomatis, Nathan D. Hatch

Theses & Dissertations

Chlamydia trachomatis (Ctr) is the leading cause of bacterial sexually transmitted infections. Ctr, a Gram-negative, obligate intracellular bacterium, develops within a membrane-bound vacuole termed an inclusion. This protective, nutrient rich, intracellular environment has allowed Ctr to undergo extensive reductive evolution – resulting in a streamlined genome of approximately 1 Mbp and the loss or fragmentation of several biosynthetic pathways, including the ability to synthesize tryptophan (Trp) de novo. During infection, the host immune system releases the cytokine IFNγ. Upon binding to a host cell, IFNγ stimulates the expression of indoleamine-2,3-dioxygenase, an enzyme capable of catabolizing cytosolic Trp, thereby starving …

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 …

Stellate Ganglion Block For Refractory Raynaud’S Phenomenon- A Case Report, William J. Naber Ii, Derik J. Scribner, Gabriel Howard

Graduate Medical Education Research Journal

Introduction: Raynaud’s phenomenon (RP) is predominately a sympathetically mediated ischemic vasospastic disease involving the distal limbs and is associated with sharp pains, numbness, and dermatological color changes. The symptoms are commonly induced by cold weather, stress, and trauma and it is known to affect 4.85% of the population. There are few well-defined treatments for patients with RP that are refractory to 1st-line therapies. We present a case of intractable RP with corresponding response to stellate ganglion block (SGB) which demonstrates the efficacy profile and safety of SNS blocks in treatment of resistant RP.

Methods: Per Bon Secours Mercy Health …

Early Onset Bullous Emphysema Associated With Polysubstance Use, Kelsey Noble, Julia Griffin

Graduate Medical Education Research Journal

The burden of COPD in the United States is tremendous. This disease is not only among the leading causes of mortality annually, but also takes a heavy financial toll.¹ Bullous emphysema is a severe variant of COPD. The primary identified risk factor for bullous emphysema is tobacco use; however, the impact of other substances is not clearly delineated.² This case presents a patient diagnosed with severe bullous emphysema at age 33 with substantial disease progression over the course of 12 years associated with much scarcer tobacco use than would be expected but a prominent history of methamphetamine and …

Systemic Inflammation Is Associated With Disease Extent And Survival In Oral Cavity Squamous Cell Carcinoma, Brendan Coutu, Dallin N. Christensen, Evan Ryan, Elizabeth Bradford Bell, Weining Zhen, Zafar Sayed

Graduate Medical Education Research Journal

Background: Although systemic immune-inflammation index (SII) correlates with patient survival in various solid malignancies limited information is available in the setting of oral cavity squamous cell carcinoma (OCSCC).

Methods: We retrospectively reviewed 222 patients who underwent a resection of curative intent for patients with OCSCC. SII was determined prior to surgical resection as platelet count × neutrophil count/lymphocyte count.

Results: At a median follow-up of 30.6 months, 2-year disease-free survival (DFS) and overall survival (OS) rates were 63.9% and 76.4%, respectively. A high SII (>1047) was associated with poor performance status and disease extent. A low SII was independently …

Pediatric Diabetic Ketoacidosis Fluid Composition And Rate In Care Of Type 1 Diabetic Patients, Gabriel Hansen, Janae Langner, Michaela Tarpley

Doctor of Nursing Practice Projects: College of Nursing

Objective

Complications of diabetic ketoacidosis (DKA) include iatrogenic hyperchloremia and acute kidney injury (AKI). The objective of this study was to evaluate the association of decreasing sodium chloride (NaCl) composition in standard DKA fluid resuscitation and the rates/severity of hyperchloremia and AKI in pediatric patients.

Methods

In December 2020, Children’s Hospital and Medical Center (CH&MC) changed the standard base composition of DKA fluids from 0.9% to 0.675% sodium chloride (NaCl) and increased the fluid resuscitation rate for patients over 30kg as a quality improvement project. A retrospective chart review analyzed patients admitted with DKA from January 2019-December 2021, excluding patients …

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 …

Cystic Duct Morphology And Heister Valves: A Cadaveric Study, Cierra R. Goerish

Theses & Dissertations

Continued occurrence of cholelithiasis, gallstones, commonly results in cholecystectomy, removal of the gallbladder. Having a comprehensive anatomical, histological, and physiological knowledge of the biliary apparatus is imperative in clinical medicine today. Additionally, the functionality of cystic duct (CD) Heister valves (HV) has been speculatory since being reported in 1732. This study summarizes the morphology, orientation, and variability of the gross biliary system and provides data to help justify HV functionality.

Cadaveric dissection was utilized for gross observation and analysis of the biliary system. The angulation of the CD was found primarily as an acute angle; however, obtuse angulation could be …

Oxidative Damage Together With Post-Occlusive Re-Oxygenation Kinetics, In Calf Muscle, Implicate Microvessels In The Myopathy Of Peripheral Artery Disease, Molly Schieber

Theses & Dissertations

Background:Peripheral Artery Disease (PAD) is characterized by calf muscle fibrosis and myofiber oxidative damage (OxD). Our laboratory has demonstrated architectural changes of calf-muscle microvessels (

Methods:Gastrocnemius biopsies were collected from controls, patients with Stage II PAD, and Stage IV patients with limb-threatening ischemia. Carbonyl adducts (CA; oxidative damage), and Heme Oxygenase-1 (HO-1; anti-OxD in microvessels) were quantified in microvessels (

Results: Post-occlusive re-oxygenation of calf muscle was slowed in Stage II patients versus controls. Kinetic parameters correlated poorly with Ankle-Brachial Index. Microvessel CA was increased in pre- and post-exercise Stage II patients and in Stage IV patients versus …

Translating A Pediatric Weight Management Intervention Into Medically Underserved Areas, Caitlin Golden

Theses & Dissertations

Despite substantial prevention and treatment efforts, childhood obesity remains a pressing public health concern. Disparities persist in obesity prevalence among children of lower socioeconomic status, racial and ethnic minority groups, and those residing in rural areas. The vast majority of efficacious pediatric weight management interventions (PWMIs) have been based in larger cities and urban areas delivered through inter-disciplinary teams in a hospital or medical center, and the degree to which these or other efficacious PWMIs have been translated to, and are feasible in, typical rural or micropolitan areas is unclear. This dissertation describes a dissemination strategy and a systematic approach …

Mechanisms Of Mutated Myosin Vb Mediated Cholestasis In Microvillus Inclusion Disease, Melissa S. Holzapfel

Theses & Dissertations

Microvillus inclusion disease (MVID) is a constitutive intestinal epithelial disease which causes definitive intestinal failure and cholestatic liver disease primarily caused by mutations in the Myosin Vb gene. Genotype-clinical phenotype associations suggest that the progression of liver disease can be predicted through a correlation between myosin Vb residual function and variable retention of bile salt transport machinery in intestinal enterocytes and liver hepatocytes. We proposed that aberrant distribution of bile salt transport proteins disrupts enterohepatic regulation of bile acids and contributes to the progression of cholestatic liver disease. To investigate the genotype-phenotype correlation, samples from MVID patients were evaluated for …

Self-Managment Of Urinary Incontinence In Women, Abbey Klein

Theses & Dissertations

Urinary incontinence is experienced by approximately 60% of adult women in the United States and negatively impacts many aspects of physical and psychological health. Many women do not seek care for urinary incontinence due to social stigma. However, those who do seek care do not often receive treatment options that align with clinical guidelines. Urinary incontinence self-management has been used interchangeably in the literature with other terms, like self-care and coping, but no conceptual definition has been delineated. The overall purpose of this dissertation was to describe urinary incontinence self-management in women. To accomplish this, a concept analysis was conducted …

Investigating Host Cell Transcriptional Heterogeneity And Metabolism In Staphylococcus Aureus Biofilm Infections, Christopher M. Horn

Theses & Dissertations

Staphylococcus aureus (S. aureus) is a leading cause of prosthetic joint infection (PJI). These infections are often intractable due to biofilm formation, which are complex bacterial communities that adhere to biotic and abiotic surfaces. Within a biofilm, there is considerable heterogeneity in bacterial metabolism and gene expression that contributes to the establishment an anti-inflammatory milieu at the site of infection, which favors bacterial persistence even in the context of an immunocompetent host. This is due, in part, to the preferential recruitment of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are a population of pathologically activated immature leukocytes that develop …

Associations Between Demographic, Social Determinant, And Health Factors And Self-Management Measures Among Insured Individuals With Type 2 Diabetes, Shari Bowers-Dueker

Capstone Experience: Master of Public Health

Background: Ensuring that individuals with type 2 diabetes properly manage their chronic condition is a nation-wide challenge, even among individuals who have health insurance coverage and access to the treatment they need. There exist several literature sources that suggest various factors that may influence an individual’s lack of self-management of type 2 diabetes. This study investigated some of these factors by determining whether various demographic, social determinant, and health factors were associated with three self-management measures among individuals with type 2 diabetes.

Methods: The self-management measures of interest included (i) whether the annual recommended two primary care visits were attended …