Digital Commons Network^™

What Is The Impact Of A Hand Hygiene Initiative On Clabsi Rates, Roshan Scaria

DNP and Student Works

This purpose of this study is to examine the effectiveness of implementing and promoting effective hand hygiene practices in preventing central line-associated bloodstream infections (CLABSIs).

Barriers To Respite Care Among African Immigrant Mothers, Yewande T. Richards

Walden Dissertations and Doctoral Studies

African immigrant children living in the United States (US) are highly susceptible to medically complex, life-limiting, and life-threatening conditions, including rheumatic heart disease, congenital heart disease, autism, and other neurodevelopmental disabilities. As primary caregivers, mothers frequently need a break from their caregiving responsibilities to experience normalcy, rest, and regenerate their reserves, which is critical to their families’ long-term stability. The purpose of this study was to understand access barriers to respite care services for these mothers and the role of race in potential disparities in access using a critical race theoretical lens. The generic qualitative research design was used with …

Challenges Faced By Early Childhood Teachers (K-2) As Schools Emerge From The Covid-19 Pandemic, Julie Christine Wright

Walden Dissertations and Doctoral Studies

Researchers have studied stress and burnout in the field of education for decades. The problem addressed in this study was that early childhood (EC) teachers of kindergarten through second grade in a large, northeastern, suburban public school district have returned to in-person instruction with many challenges related to the COVID-19 pandemic. The purpose of this basic qualitative study was to explore the personal and professional challenges experienced by EC teachers and investigate the support they need to remain in the classroom. Jennings and Greenberg’s prosocial classroom model was the conceptual framework of the study. Two research questions explored the challenges …

Single Extracellular Vesicle Imaging And Computational Analysis Identifies Inherent Architectural Heterogeneity, Kshipra S Kapoor, Seoyun Kong, Hikaru Sugimoto, Wenhua Guo, Vivek Boominathan, Yi-Lin Chen, Sibani Lisa Biswal, Tanguy Terlier, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Evaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM), which has an inherent ability to image biological samples without harsh labeling methods while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources, such as cancer cells, normal cells, immortalized cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by …

Using Digital Twins To Protect Biomanufacturing From Cyberattacks, Brenden Fraser-Hevlin, Alec W. Schuler, B. Arda Gozen, Bernard J. Van Wie

Military Cyber Affairs

Understanding of the intersection of cyber vulnerabilities and bioprocess regulation is critical with the rise of artificial intelligence and machine learning in manufacturing. We detail a case study in which we model cyberattacks on network-mediated signals from a novel bioreactor, where it is important to control medium feed rates to maintain cell proliferation. We use a digital twin counterpart reactor to compare glucose and oxygen sensor signals from the bioreactor to predictions from a kinetic growth model, allowing discernment of faulty sensors from hacked signals. Our results demonstrate a successful biomanufacturing cyberattack detection system based on fundamental process control principles.

Helper T Cell Immunity In Humans With Inherited Cd4 Deficiency., Antoine Guérin, Marcela Moncada-Vélez, Katherine Jackson, Masato Ogishi, Jérémie Rosain, Mathieu Mancini, David Langlais, Andrea Nunez, Samantha Webster, Jesse Goyette, Taushif Khan, Nico Marr, Danielle T Avery, Geetha Rao, Tim Waterboer, Birgitta Michels, Esmeralda Neves, Cátia Iracema Morais, Jonathan London, Stéphanie Mestrallet, Pierre Quartier Dit Maire, Bénédicte Neven, Franck Rapaport, Yoann Seeleuthner, Atar Lev, Amos J Simon, Jorge Montoya, Ortal Barel, Julio Gómez-Rodríguez, Julio C Orrego, Anne-Sophie L'Honneur, Camille Soudée, Jessica Rojas, Alejandra C Velez, Irini Sereti, Benjamin Terrier, Nancy Marin, Luis F García, Laurent Abel, Stéphanie Boisson-Dupuis, Joel Reis, Antonio Marinho, Andrea Lisco, Emilia Faria, Christopher C Goodnow, Julia Vasconcelos, Vivien Béziat, Cindy S Ma, Raz Somech, Jean-Laurent Casanova, Jacinta Bustamante, Jose Luis Franco, Stuart G Tangye

Faculty Research 2024

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαβ+CD4-CD8- T cells, which phenotypically …

Therapeutic Advances In The Management Of Type Ii Diabetes, Ashfod Mukula

Senior Honors Theses

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by persistent hyperglycemia. This condition occurs due to two main factors: β-cell dysfunction and reduced response to insulin by cells and tissues with insulin receptors (insulin resistance). Insulin resistance occurs when the body fails to respond to insulin; therefore, cells and tissues are impaired in transporting glucose, leading to abnormally high glucose levels in circulation. Insulin resistance is a multifactorial condition; thus, the eminent cause is not fully known. Individual health conditions and genetic predisposition have been postulated to cause it. Molecularly, insulin resistance has been associated with complications in …

Measuring The Effects Of Selenium Exposure On Batrachochytrium Dendrobatidis (Bd) Growth In Vivo In Larval American Bullfrogs (Rana Catesbeiana)., Taylor Morrison

Honors Thesis

Most amphibians in today’s world are exposed to a variety of environmental stressors. This project’s main objective was to determine any effects of selenium on Batrachochytrium dendrobatidis (Bd) and infection levels in South Dakota amphibians. I selected American bullfrogs (Rana catesbeiana) as they are susceptible to Bd and are found throughout eastern South Dakota. The secondary objective of this project was to measure any impact of Bd and selenium, combined, on growth measures of the frogs. The third objective was to see if survival rates were reduced when amphibians were exposed to Bd and selenium. Tadpoles were collected (n=225) from …

Serine Deamination By Human Serine Racemase Synergizes With Antibiotics To Curtail The Replication Of Chlamydia Trachomatis, Patricia D. Mott, Arnold H. Zea, Jamiya Lewis, Oygul Mirzalieva, Ashok A. Aiyar

School of Medicine Faculty Publications

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates …

Does Point-Of-Care Ultrasound Affect Fluid Resuscitation Volume In Patients With Septic Shock: A Retrospective Review, Enyo A Ablordeppey, Amy Zhao, Jeffery Ruggeri, Ahmad Hassan, Laura Wallace, Mansi Agarwal, Sean P Stickles, Christopher Holthaus, Daniel Theodoro

2020-Current year OA Pubs

BACKGROUND: Fixed, large volume resuscitation with intravenous fluids (IVFs) in septic shock can cause inadvertent hypervolemia, increased medical interventions, and death when unguided by point-of-care ultrasound (POCUS). The primary study objective was to evaluate whether total IVF volume differs for emergency department (ED) septic shock patients receiving POCUS versus no POCUS.

METHODS: We conducted a retrospective observational cohort study from 7/1/2018 to 8/31/2021 of atraumatic adult ED patients with septic shock. We agreed upon

RESULTS: 304 patients met criteria and 26% (78/304) underwent POCUS. Cardiac POCUS demonstrated reduced ejection fraction in 15.4% of patients. Lung ultrasound showed normal findings in …

Don't Throw Away Your Shot, Eric F. Spina

President's Blog: From the Heart

Good morning CLASS OF 2024!! And what a joyous morning it is! Congratulations to each and every one of you! Now ... take a deep breath. Pause. Exhale. And let the realization of this moment wash over you. You. Did. It! You are GRADUATING from the University of Dayton!

Implementation Of An Algorithm To Reduce Wait Times For College-Aged Women Presenting With Uti Symptoms, Mallory Beck, Miranda Neu

Doctor of Nursing Practice Projects: College of Nursing

Urinary tract infections, UTIs, are among the most common reasons college-aged women seek medical care. The selected University clinic has a difficult time triaging walk-in UTI patients promptly. Long patient wait times have a negative effect on patient and employee satisfaction scores. An algorithm was created to assist the University clinic in triaging walk-in UTI patients using guidelines from the American Academy of Family Physicians updated with the most current clinical practice recommendations. The algorithm includes the utilization of a point-of-care urine analyzer which provides urinalysis results in 120 seconds. With the algorithm and point-of-care urine analyzer, the student health …

The Physiological Significance Of Nitric Oxide Synthase In Staphylococci, Ryan M. Singh

Theses & Dissertations

Staphylococci, particularly Staphylococcus epidermidis, are common causes of implant-associated infections that may result in notable morbidity and mortality. One of the ways the innate immune system attempts to combat these invading pathogens is via the respiratory burst, in which free radical species such as nitric oxide (NO^•), toxic to bacterial respiration, are released in large quantities. Despite the toxicity of NO^•, some bacteria, including staphylococci, encode an endogenous bacterial nitric oxide synthase (bNOS), whose physiological role has been unclear until now. In this dissertation, we demonstrate that S. epidermidis is able to overcome the toxicity …

Impact Of Nutritional Status And Placental Malaria Infection On Pregnancy Outcome In A Population Of Nigerian Maternal-Infant Dyads, Shirley F. Delair

Theses & Dissertations

Nigeria is the most populous country in Africa and accounts for one-quarter of the newborn mortality on the continent. Most newborn deaths are from prematurity (33%), infections (33%), and intrapartum complications (31%). Using an adapted analytical framework for the study of child survival in developing countries, this dissertation aimed to look at the pregnancy outcome of a population of Nigerian women and their offspring by looking at proximate determinants of health from nutritional status and environmental conditions. In Chapter 1, we characterized the micronutrients of the mother-infant dyads, looking specifically at concentrations of vitamin D and its metabolites. In Chapter …

Bridging The Information Divide: Leveraging The Learning Health System To Understand Rural-Urban Health Disparities In The Covid-19 Era, Alfred J. Anzalone

Theses & Dissertations

The examination of healthcare disparities, which the COVID-19 pandemic exacerbated, revealed a pronounced divide between rural and urban settings. This divide particularly underscored the challenges of integrating rural healthcare into the Learning Health System (LHS) and utilizing real-world data (RWD) in response to a public health emergency. Our investigation expanded the growing body of literature on the rural mortality penalty, encompassing the period following the COVID-19 pandemic. By employing an LHS-enabled centralized platform of RWD, we assessed the impact of rurality on adverse COVID-19 outcomes (Aim 1), focusing on inpatient adverse events and the effectiveness of treatments and vaccinations across …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …

A Tale Of Two Proteins: An Investigation Of Recruitment Of Eukaryotic Proteins Fli1 And Lrrf1 To The Chlamydial Inclusion Membrane, Natalie Sturd

Theses & Dissertations

Chlamydia trachomatis is the pathogen responsible for the majority of infectious blindness and sexually transmitted bacterial infections worldwide. As an obligate intracellular pathogen, it establishes a niche within a pathogen-specific vacuole, termed the chlamydial inclusion. C. trachomatis modifies the inclusion membrane by type III secretion and insertion of effectors known as inclusion membrane proteins, or Incs. These Inc proteins are critical for chlamydial pathogenesis via their interactions with host proteins and their capacity to stabilize the inclusion membrane. Previous studies from our lab demonstrated the localization of two eukaryotic proteins, Flightless 1 (FLI1) and its binding partner leucine-rich repeat interacting …

Mucins: Drivers Of Cancer Cell And Microenvironment Crosstalk In Pancreatic Cancer, Xiaoqi Li

Theses & Dissertations

Mucins facilitate the pancreatic cancer (PC) initiation, progression, and metastasis. Among mucins, MUC4 has been reported to inhibit lymphokine-activated cell killing and induce the apoptosis of cytotoxic T-cells. Counterintuitively, MUC4 expression is upregulated by multiple T-cell-secreted cytokines, such as IFN-γ, IL-17, and stroma-secreted factors like retinoic acid. Previously, we have identified that nuclear receptor coactivator 3 (NCOA3) regulates the MUC1 and MUC4 expression by increasing chromatin accessibility and maintaining protein stability. However, the comprehensive crosstalk mediated by MUC4 in cancer cells and T-cells and how its upstream regulator, NCOA3, modifies the cancer cell-intrinsic behavior is still elusive. Here, we show …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Genetic Drivers And Tumor Milieu Analysis In Mantle Cell Lymphoma, Sunandini Sharma

Theses & Dissertations

Mantle Cell Lymphoma (MCL) is a B-cell lymphoma characterized by t(11;14) leading to CyclinD1 (CCND1) overexpression with highly variable clinical response. Although the tumor intrinsic mechanisms have been fairly studied, the role of the tumor microenvironment (TME) in survival and therapeutic responses is marginally examined. Herein, we integrated high-throughput genomics and characterized TME using a highly multiplexed, spatially resolved, single-cell digital pathology approach termed imaging mass cytometry (IMC) to delineate the tumor-immune landscape. We identified eight MCL genomic subtypes with distinct signatures and prognoses. Subsets C2, C5, and C6 had poorer outcomes with a 5-year overall survival (OS) of 33-50% …

Pharmacodynamic Effects Of Zsj-0228 On Complement Protein Deposition In The Kidneys Of Focal Segmental Glomerulosclerosis-Afflicted Mice., Braeden Pinkerton

Theses & Dissertations

Chronic inflammation, when left untreated, may result in significant morbidity and in severe cases, mortality. While glucocorticoids (GCs) are still being extensively used clinically as a class of very potent anti-inflammatory agents, they are also notorious for diverse adverse side effects. To mitigate these side effects, we have developed a polyethylene glycol (PEG)-based prodrug (ZSJ-0228) of dexamethasone (Dex). When tested on rodent models of Lupus Nephritis and Focal Segmental Glomerulosclerosis (FSGS), ZSJ-0228 was found to provide potent and sustained therapeutic efficacy without any detectable typical GC-associated side effects. Given ZSJ-0228’s transient renal exposure after systemic administration, it is yet to …

Gene Co-Expression And Machine Learning Approaches To Compare Sars-Cov-2 Infected Tissues In Humans, Sahil Sethi

Theses & Dissertations

The global outbreak of COVID-19, triggered by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spurred an urgent need for a deeper comprehension of the molecular mechanisms involved in the host-virus interactions. Despite advancements in transcriptomic technology and computational resources, limited attention has been given to the holistic integration of molecular and clinical data to characterize the genotype/phenotype aspects of the disease.

This study analyzes gene expression patterns in various tissues, including the lung, nasal, blood, and placenta, in patients with COVID-19 to identify differentially regulated genes and pathways. We also evaluated organ-specific gene co-expression patterns that …

Viral Hepatitis And Hiv Screening Amongst Inpatients With Substance Use Disorder, Christine Papastamelos, Md, Elizabeth Novick, Md, Carolyn Kramer, Md, John Zurlo,Md, Nikhil Seval, Md, Daniel Taupin, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• ~67,000 individuals in Philadelphia county are estimated to be living with opioid use disorder (OUD).¹
• Persons who inject drugs (PWID) are at disproportionately greater risk of acquiring HIV and viral hepatitis compared to the general public.²
• PWID are less likely to receive timely HIV and viral hepatitis screening in the outpatient setting given complex biopsychosocial barriers, including homelessness, mental illness, lack of insurance, incarceration, and stigma.^3,4

Medication Access Barriers To Hepatitis C Anti-Viral Therapy Following Transplantation Of Hepatitis C Positive Donors Into Hepatitis C Negative Recipients, Harry Rockower, Md, Sarah Yeager, Pharmd, Jami Schulte, Pharmd, Dagan Coppock, Md, Jonathan Fenkel, Md, Katherine Belden, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Over the past decade there has been a paradigm shift in solid organ transplantation with the use of Hepatitis C (HCV) positive donor organs for HCV negative recipients.
• This evaluation looks through the lens of insurance approval for direct acting antivirals (DAA) and the process needed for obtaining and ensuring affordability of these medications.
• While the AASLD/IDSA guidelines recommend early initiation of pangenotypic DAA therapy after organ transplant without the need to confirm recipient viral replication many centers often initiate the DAA approval process after viremia is detected due to insurance barriers.¹
• The process for obtaining insurance approval …

Streamlined Pre-Authorization Expedites Patient Discharges From Stroke Units To Rehabilitation Centers, Michael Vo, William Nguyen, Matthew Trotter, Jeffrey Zhou, Glenn A. Gonzalez, Eric Mong, Rene Daniel, Ross-Jordan Elliott, James Harrop

Health Equity and Quality Improvement (HEQI) Summit

Background

Problem statement: Patient discharge from neurosurgical stroke units to rehabilitation centers is a complex administrative and clinical endeavor involving a population often with cognitive and motor morbidity that can be intensified with extensive hospital length of stay (LOS).

Project aim: This project aims to analyze the change in LOS due to the introduction of liaisons, who advocate for and expedite pre-authorization, rounds, and plan of care establishment for patients with strokes.

Optimizing Resource Allocation Of A Covid-19 Prophylactic In Immunocompromised Hosts, Julianna Tolotta, Abigail Hoover, Michael Joseph, Angelinia Liddy, Anshel Kenkare, Dagan Coppock

Health Equity and Quality Improvement (HEQI) Summit

Introduction

• COVID-19 presented unique challenges for the care of immunocompromised individuals.
• Patients with suppressed immune systems lack the ability to mount a robust response to vaccines, leading to an increased likelihood of developing severe COVID-19 responses and increased mortality.
• Astra-Zeneca developed Evusheld, a monoclonal antibody (Tixagevimab/cilgavimab) as a COVID-19 prophylaxis to target the SARS-CoV-2 spike protein.¹
• In December 2023, the FDA enacted an Emergency Use Authorization (EUA) for Evusheld in immunocompromised individuals and TJUH developed a roll-out plan.²
• Thomas Jefferson University Health (TJUH) distributed the drug using a tiering system that ranked the degrees of immunocompromising conditions for …

Public And Community Perceptions Of Safe Injection Sites, Bahram Pashaee, Mph, Gary Kaplan, Mslis, Amy Leader, Drph, Mph

Health Equity and Quality Improvement (HEQI) Summit

Background

• The opioid epidemic began in 1999 and the number of deaths from overdoses has since quadrupled by 2019
• 50,000 deaths in the US in 2019 from opioid overdoses and the numbers increase each year
• Research Question: What are the public’s and communities' perceptions of safe injection sites?

Parental Knowledge Of Signs, Symptoms, And Risk Factors Associated With Sudden Cardiac Arrest In Adolescent Athletes, Lisa A. Lattera-Hughes

Walden Dissertations and Doctoral Studies

Exercise is associated with unmasking underlying cardiac disorders and increasing an athlete’s risk for experiencing a sudden cardiac arrest (SCA) event during sports. Parental knowledge is an important component of health education in relation to the future of their child’s health. The purpose of this quantitative research study was to assess the relationship between parental knowledge about warning signs, symptoms, and risk factors associated with SCA in adolescent athletes and parental willingness to participate in an educational intervention to learn about SCA. The theoretical framework was based on Nutbeam’s conceptual model of health literacy. Eightyone parents whose adolescent children participated …

Toxicological Impacts Of River Chemical Spills In Affected West Virginia Counties, Janice Lorraine Taylor Peters

Walden Dissertations and Doctoral Studies

Factors such as geographical location/proximity and exposure to external environmental events, as well as poor regulatory processes, are known to increase the risk for cancers among affected populations. There is still a gap in the literature related to the incidence of cancers in specific regions with heavy industrialization and environmental health hazards. In West Virginia, chemical contamination events have occurred in or near water systems. The goal of this quantitative, retrospective study was to discover whether there were any differences in the incidence of disease or adverse health effects and cancers due to chemical contamination in four counties (Kanawha, Mingo, …

Understanding The Non-Canonical Regulation Of Srebp In Aspergillus Fumigatus, Muhammad Abubakar Khan

Dartmouth College Ph.D Dissertations

Aspergillus fumigatus is an opportunistic fungal pathogen causing invasive pulmonary aspergillosis (IPA), with high mortality rates in immunocompromised individuals. Adaptation to the hypoxic microenvironment of IPA is crucial for fungal virulence. The transcription factor SrbA, a Sterol Regulatory Element-Binding Protein (SREBP) homolog, plays a key role in this hypoxic response and regulates genes involved in hypoxic growth, sterol biosynthesis, and azole resistance, making it an attractive therapeutic target.

However, SrbA activation in A. fumigatus lacks critical components of the canonical SREBP pathway, such as SCAP, Site-1 protease (S1P), and Site-2 protease (S2P). Instead, the rhomboid protease RbdB, signal peptide peptidase …