Digital Commons Network^™

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Monocyte Anti-Inflammatory Activity Is Dictated By Metabolic Status During Staphylococcus Aureus Biofilm Infection, Kelsey J. Yamada

Theses & Dissertations

Staphylococcus aureus biofilms represent a significant cause of morbidity and economic burden and are often associated with nosocomial infections, including medically implanted devices. In particular, prosthetic joint infections (PJIs) are a growing concern due to the continued increase in orthopedic procedures. Staphylococcal species cause >50% of all PJIs, while S. aureus represents the most invasive and associated with the most morbidity. S. aureus-associated biofilm infections are recalcitrant to antibiotic therapy, due to both the acquisition of genetic elements and metabolic dormancy. Furthermore, S. aureus biofilm infections remain chronic because they cannot be cleared by the immune system. Recent studies …

Developing Targeted Therapy Against Pancreatic Cancer, Garima Kaushik

Theses & Dissertations

Not available.

Common Areas For Improvement From After Action Reports (Aars) Generated After Exercises Or Actual Disasters, As Reported By A National Sample Of U.S. Hospitals, Abdoulaye Abdoulaziz

Theses & Dissertations

Many hospitals conduct exercises every year, and they conclude the process with an After-Action Report and Improvement Plan. Therefore, there are thousands of AAR/IP’s across the country with limited opportunity to compare them or to learn from them collectively. Our project has gathered Improvement Plans (IP’s) and conducted a qualitative analysis which determined whether the “lessons learned” can be categorized into common themes.

The Association Between Neurocognitive Impairment And Health-Related Quality Of Life Among People Living With Human Immunodeficiency Virus (Hiv)., Philip S. Amara

Capstone Experience: Master of Public Health

Background: Despite the use of combination antiretroviral therapy, HIV associated neurocognitive impairment (NCI) persists in HIV seropositive persons, albeit in milder forms than before therapy was available. Nevertheless, the relationship between NCI and health-related quality of life (HRQoL) is not well known.

Method: Baseline data from the CHARTER study was used to investigate the association between NCI and HRQoL. Factor analysis was employed to summarize the 35-item Medical Outcome Survey questionnaire into physical and mental HRQoL scores. General linear models were employed to investigate the association between NCI, as measured by global deficit scores (GDS), and HRQoL, and to control …

Evaluation Of A Community Health Worker Intervention On Rates Of Measles, Mumps And Rubella Immunization In A Somali Population In Lexington, Nebraska, Melanie Menning

Capstone Experience: Master of Public Health

Measles is a highly contagious viral disease. It remains an important cause of death among young children globally, despite the availability of a safe and effective vaccine.

There have been increasing outbreaks of measles to waning immunization. This study sought to evaluate rates of Measles, Mumps and Rubella (MMR) immunization in a Somali population living in Lexington, Nebraska and to evaluate a community health worker intervention to improve immunization rates. NESIIS data for Lexington Regional Health Center (LRHC) was queried to assess MMR trends for all clinic patients between 15 and 72 months both before and after implementation of the …

Improving Antimicrobial Stewardship Programs In Small Community Hospitals Through An Assessment And Feedback Model, Philip Chung, Kate Tyner, Scott Bergman, Terry Micheels, Mark Rupp, Michelle Schwedhelm, Maureen Tierney, Muhammad Salman Ashraf, Trevor Van Schooneveld

Posters and Presentations: Nebraska ASAP

Small community hospitals often lack expertise and resources for antimicrobial stewardship program implementation. Using an assessment-and-feedback model, Nebraska ASAP performed onsite assessment of antimicrobial stewardship efforts in 5 small community hospitals and provided facility specific feedback on implementation/augmentation of antimicrobial stewardship program. As a result of this model, participating small community hospitals were able to increase the number of antimicrobial stewardship core elements implemented while reducing antibiotic use and incidence of CDI.

Consequences Of Pathogen Lists: Why Some Diseases May Continue To Plague Us, David Brett-Major, Trina Racine, Gary P. Kobinger

Journal Articles: Epidemiology

The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular …

Effect Of Abo Blood Group On Asymptomatic, Uncomplicated And Placental Plasmodium Falciparum Infection: Systematic Review And Meta-Analysis, Abraham Degarege, Merhawi T. Gebrezgi, Consuelo M. Beck-Sague, Mats Wahlgren, Luiz Carlos De Mattos, Purnima Madhivanan

Journal Articles: Epidemiology

BACKGROUND: Malaria clinical outcomes vary by erythrocyte characteristics, including ABO blood group, but the effect of ABO blood group on asymptomatic, uncomplicated and placental Plasmodium falciparum (P. falciparum) infection remains unclear. We explored effects of ABO blood group on asymptomatic, uncomplicated and placental falciparum infection in the published literature.

METHODS: A systematic review and meta-analysis was performed using the preferred reporting items for systematic reviews and meta-analyses guidelines. Articles in Pubmed, Embase, Web of Science, CINAHL and Cochrane Library published before February 04, 2017 were searched without restriction. Studies were included if they reported P. falciparum infection incidence or prevalence, …

Controlling Latent Tb Tuberculosis Infection In High-Burden Countries: A Neglected Strategy To End Tb, Gavin J. Churchyard, Susan Swindells

Journal Articles: Infectious Diseases

In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries.

Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, Mckenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic …

Mapping Of Lymphatic Filariasis In Loiasis Areas: A New Strategy Shows No Evidence For Wuchereria Bancrofti Endemicity In Cameroon, Samuel Wanji, Mathias Eyong Esum, Abdel Jelil Njouendou, Amuam Andrew Mbeng, Patrick W Chounna Ndongmo, Raphael Awah Abong, Jerome Fru, Fanny F. Fombad, Gordon Takop Nchanji, Glory Ngongeh, Narcisse V. Ngandjui, Peter Ivo Enyong, Helen Storey, Kurt C. Curtis, Kerstin Fischer, Joseph R. Fauver, Daphne Lew, Charles W. Goss, Peter U. Fischer

Journal Articles: Epidemiology

BACKGROUND: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate.

METHODOLOGY/PRINCIPAL FINDINGS: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses …

Acceptability And Feasibility Of A Pharmacist-Led Hiv Pre-Exposure Prophylaxis (Prep) Program In The Midwestern United States, Joshua P. Havens, Kimberly Scarsi, Harlan Sayles, Donald G. Klepser, Susan Swindells, Sara H. Bares

Journal Articles: Infectious Diseases

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition, yet significant barriers exist to its prescription and use. Incorporating pharmacists in the PrEP care process may help increase access to PrEP services.

METHODS: Our pharmacist-led PrEP program (P-PrEP) included pharmacists from a university-based HIV clinic, a community pharmacy, and two community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended CDC guidelines, and authorized emtricitabine-tenofovir disoproxil fumarate prescriptions. Demographics and retention in care over 12 months were summarized and participant satisfaction and pharmacist acceptability with the P-PrEP …

Next-Generation Sequencing Of Hiv-1 Single Genome Amplicons, Gustavo H. Kijak, Eric Sanders-Buell, Phuc Pham, Elizabeth A. Harbolick, Celina Oropeza, Anne Marie O'Sullivan, Meera Bose, Charmagne G. Beckett, Mark Milazzo, Merlin L. Robb, Sheila A. Peel, Paul T. Scott, Nelson L. Michael, Adam W. Armstrong, Jerome H. Kim, David Brett-Major, Sodsai Tovanabutra

Journal Articles: Epidemiology

The analysis of HIV-1 sequences has helped understand the viral molecular epidemiology, monitor the development of antiretroviral drug resistance, and design candidate vaccines. The introduction of single genome amplification (SGA) has been a major advancement in the field, allowing for the characterization of multiple sequences per patient while preserving linkage among polymorphisms in the same viral genome copy. Sequencing of SGA amplicons is performed by capillary Sanger sequencing, which presents low throughput, requires a high amount of template, and is highly sensitive to template/primer mismatching. In order to meet the increasing demand for HIV-1 SGA amplicon sequencing, we have developed …

Using "Outbreak Science" To Strengthen The Use Of Models During Epidemics., Caitlin Rivers, Jean-Paul Chretien, Steven Riley, Julie A. Pavlin, Alexandra Woodward, David Brett-Major, Irina Maljkovic Berry, Lindsay Morton, Richard G. Jarman, Matthew Biggerstaff, Michael A. Johansson, Nicholas G. Reich, Diane Meyer, Michael R. Snyder, Simon Pollett

Journal Articles: Epidemiology

Infectious disease modeling has played a prominent role in recent outbreaks, yet integrating these analyses into public health decision-making has been challenging. We recommend establishing ‘outbreak science’ as an inter-disciplinary field to improve applied epidemic modeling.

New Filovirus Disease Classification And Nomenclature, Jens H. Kuhn, Takuya Adachi, Neill K.J. Adhikari, Jose R. Arribas, Ibrahima Elhadj Bah, Daniel G. Bausch, Nahid Bhadelia, Matthias Borchert, Arne Broch Brantsæter, David Brett-Major, Timothy H. Burgess, Daniel S. Chertow, Christopher G. Chute, Theodore J. Cieslak, Robert Colebunders, Ian Crozier, Richard T. Davey, Hilde De Clerck, Rafael Delgado, Laura Evans, Mosoka Fallah, William A. Fischer, Tom E. Fletcher, Robert A. Fowler, Thomas Grünewald, Andy Hall, Angela L. Hewlett, Andy I.M. Hoepelman, Catherine F. Houlihan, Giuseppe Ippolito, Shevin T. Jacob, Michael Jacobs, Robert Jakob, Frederique A. Jacquerioz, Laurent Kaiser, Andre C. Kalil, Rashidatu F. Kamara, Jimmy Kapetshi, Hans-Dieter Klenk, Gary Kobinger, Mark G. Kortepeter, Colleen S. Kraft, Thomas Kratz, Henry S. Kyobe Bosa, Marta Lado, François Lamontagne, H. Cliff Lane, Leslie Lobel, Julius Lutwama, G. Marshall Lyon, Moses B.F. Massaquoi, Thomas A. Massaquoi, Aneesh K. Mehta, Vital Mondonge Makuma, Srinivas Murthy, Tonny Seikikongo Musoke, Jean-Jacques Muyembe-Tamfum, Phiona Nakyeyune, Carolina Nanclares, Miriam Nanyunja, Justus Nsio-Mbeta, Tim O'Dempsey, Janusz T. Pawęska, Clarence J. Peters, Peter Piot, Christophe Rapp, Bertrand Renaud, Bruce Ribner, Pardis C. Sabeti, John S. Schieffelin, Werner Slenczka, Moses J. Soka, Armand Sprecher, James Strong, Robert Swanepoel, Timothy M. Uyeki, Michel Van Herp, Pauline Vetter, David A. Wohl, Timo Wolf, Anja Wolz, Alie H. Wurie, Zabulon Yoti

Journal Articles: Epidemiology

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.

De Novo Assembly Of The Brugia Malayi Genome Using Long Reads From A Single Minion Flowcell, Joseph R. Fauver, John Martin, Gary J. Weil, Makedonka Mitreva, Peter U. Fischer

Journal Articles: Epidemiology

Filarial nematode infections cause a substantial global disease burden. Genomic studies of filarial worms can improve our understanding of their biology and epidemiology. However, genomic information from field isolates is limited and available reference genomes are often discontinuous. Single molecule sequencing technologies can reduce the cost of genome sequencing and long reads produced from these devices can improve the contiguity and completeness of genome assemblies. In addition, these new technologies can make generation and analysis of large numbers of field isolates feasible. In this study, we assessed the performance of the Oxford Nanopore Technologies MinION for sequencing and assembling the …

Risk Mitigation For Travelers: Managing Endemic And Emerging Threats, Shannon M. Wood, David Brett-Major

Journal Articles: Epidemiology

International travel continues to increase in numbers and complexity. Despite the availability of pretravel health advice, travelers remain at risk for exposure to common organisms as well as emerging pathogens. With low rates of travel clinic utilization, it is important for the general practitioner to remain aware of the importance of travel health, risk factors unique to individual patients, and evolving threats. This review highlights important considerations when evaluating ill travelers, incorporating emerging infectious threats.

Characterization Of The Plasma Proteome Of Nonhuman Primates During Ebola Virus Disease Or Melioidosis: A Host Response Comparison, Michael D. Ward, Ernst E. Brueggemann, Tara Kenny, Raven E. Reitstetter, Christopher R. Mahone, Sylvia Trevino, Kelly Wetzel, Ginger C. Donnelly, Cary Retterer, Robert B. Norgren, Rekha G. Panchal, Travis K. Warren, Sina Bavari, Lisa H. Cazares

Journal Articles: Genetics, Cell Biology & Anatomy

Background: In-depth examination of the plasma proteomic response to infection with a wide variety of pathogens can assist in the development of new diagnostic paradigms, while providing insight into the interdependent pathogenic processes which encompass a host's immunological and physiological responses. Ebola virus (EBOV) causes a highly lethal infection termed Ebola virus disease (EVD) in primates and humans. The Gram negative non-spore forming bacillus

Methods: Herein we report the quantitative proteomic analysis of plasma collected at various times of disease progression from 10 EBOV-infected and 5

Results: A total of 41 plasma proteins displayed significant alterations in abundance during EBOV …

Csf Inflammatory Markers Differ In Gram-Positive Versus Gram-Negative Shunt Infections., Gwenn Skar, David Synhorst, Matthew K. Beaver, Jessica N. Snowden

Journal Articles: Pediatrics

BACKGROUND: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection.

METHODS: We conducted a retrospective chart review of children with …

Human-Like Nsg Mouse Glycoproteins Sialylation Pattern Changes The Phenotype Of Human Lymphocytes And Sensitivity To Hiv-1 Infection, Raghubendra S. Dagur, Amanda Branch-Woods, Saumi Mathews, Poonam S. Joshi, Rolen M. Quadros, Donald W. Harms, Yan Cheng, Shana M. Miles, Samuel J. Pirruccello, Channabasavaiah B. Gurumurthy, Santhi Gorantla, Larisa Y. Poluektova

Journal Articles: Munroe-Meyer Institute

BACKGROUND: The use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases such as HIV-1 and to investigate multiple aspects of human immune system development. However, mouse and human are different in sialylation patterns of proteins due to evolutionary mutations of the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene that prevent formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. How changes in the mouse glycoproteins' chemistry affect phenotype and function of transplanted human hematopoietic stem cells and mature human immune cells in the course of HIV-1 infection are not known.

RESULTS: We mutated mouse …

Patient Care In High-Level Containment Care Units: In A Resourced Setting, Angela M. Vasa, Kate C. Boulter, Jolene M. Horihan, David S. Cates, Craig A. Piquette, James N. Sullivan, Daniel W. Johnson, Angela L. Hewlett

Books and Book Chapters: Nebraska Medicine

Vasa, A., Boulter, K., Horihan, Cates, D., Piquette, C., Sullivan, J., Johnson, D, & Hewlett, A. (2019). Patient Care in High-Level Containment Care Units. In T. Cieslak, M. Kortepeter, C. Kratochvil, & J. Lawler (Eds.), Nebraska Isolation and Quarantine Manual (pp. 87-101). Lincoln, NE: University of Nebraska Press.

Development Of Macromolecular Prodrugs For The Treatment Of Chronic Inflammatory Pain, Laura Weber

Theses & Dissertations

Chronic pain afflicts millions of people worldwide. Particularly, the inflammatory conditions in the incurable disease rheumatoid arthritis (RA) generate persistent pain in its sufferers, for which a number of different analgesics have been prescribed, such as glucocorticoids (GCs) and opioids. However, administration of these pain- mitigating pharmaceutics is implicated in the development of adverse systemic effects due to their non-specific tissue distribution and quick excretion, eliciting the need for high dosing frequencies. To address this issue, this thesis is focused on the development of prodrugs based on a macromolecular design approach to instill preferential inflammation-targeting and retentive properties to common …

Association Between Systemic Inflammation And Nutritional Compounds In Maternal-Infant Dyads, Jessica N. Snowden

Theses & Dissertations

Many events during pregnancy and early infancy can affect infant brain development. Inflammation during pregnancy, around delivery and during early infancy appears to adversely affect infant brain development. As the brain is rapidly growing and developing from conception through early childhood, it is particularly vulnerable during this time to inflammatory insults, which may be exacerbated or ameliorated by nutritional factors. Inflammatory compounds, as well as many nutritional compounds, can be either pro- or anti-inflammatory. These compounds are of particular importance in preterm infants, who are at risk of deficiency in anti-inflammatory micronutrients typically stored as a result of prenatal maternal …

Surveillance, Prevention And Surgical Treatments For Hepatocellular Carcinoma, Kerui Xu

Theses & Dissertations

Liver cancer is the second-leading cause of cancer death, representing roughly 9.1% of all cancer mortality. Of all primary cancers of the liver, hepatocellular carcinoma (HCC) accounts for roughly 85%. HCC has been increasing in the U.S. and other countries. In particular, HCC places a huge burden on the Chinese population, as China alone consists of approximately 50% of the total HCC cases and deaths. In China, chronic hepatitis B virus (HBV) infection is the leading cause for developing HCC. The two challenges in prevention and control of HCC experienced in China are low rates of HCC screening among the …

An Assessment Of Preparations Made In The United States For Highly Hazardous Communicable Diseases Following The 2014-2016 Ebola Virus Disease Epidemic, Jocelyn J. Herstein

Theses & Dissertations

The 2014-2016 Ebola virus disease (EVD) epidemic in West Africa was unprecedented in magnitude and scope. The threat of imported cases of EVD in the United States prompted the Centers for Disease Control and Prevention (CDC) to establish a tiered network of hospitals to enhance domestic isolation capacity, including the designation of select hospitals as Ebola treatment centers (ETCs). As of spring 2015, no information existed on the capacity, physical infrastructure, staffing models, or infection control protocols of these newly-established ETCs, nor was there information on other highly hazardous communicable diseases (HHCDs) these units would admit. Moreover, no documentation was …

Factors Associated With Follow-Up Compliance Among Clients Referred By A Local Health Department For Hiv Pre-Exposure Prophylaxis, Lauren R. Cirrincione

Capstone Experience: Master of Public Health

Background: Pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) is a public health strategy to limit HIV infection among at-risk populations. Local health departments (LHDs) promote PrEP initiation by referring patients to private and academic specialty care centers. However, low follow-up compliance remains a challenge in this setting. Between January 2016 and September 2018, Douglas County Health Department, a LHD in Omaha, Nebraska, externally referred 126 clients for PrEP at an academic specialty care center, and only 20 (15%) clients completed a PrEP initiation follow-up appointment. The purpose of this study is to describe the characteristics of clients referred by …

Examining The Impact Of Hiv Medical And Social Case Management Program On Viral Load For Clients Living With Hiv/Aids In Nebraska, Abdulla Munir

Capstone Experience: Master of Public Health

Abstract

Case management (CM) is one of the standard practices that has been implemented since 1990 to help people living with HIV/AIDS (PLWHA) in the United States. The program is designed for low-income populations and it aims to address the barriers related to access to health care and improve the HIV outcomes. Previous studies identified a positive association with the provision of CM and improvement in viral outcomes. Increasing the viral suppression rates among HIV diagnosed individuals proved to reduce the risk of transmitting the infection, and disease incidence. Although CM program is provided to Nebraskans diagnosed with HIV, but …

Burden And Risk Factors Associated With Hcv Infection Among People Living With Hiv Infection In Nebraska: Population-Based Cross-Sectional Study From 1997 To 2017, Issaka Kabore

Capstone Experience: Master of Public Health

Background: Previous studies have shown high prevalence of HCV infection among people living with HIV infection. Coinfected people are at risk of developing liver diseases resulting an increase rate of mortality. Several risk factors for HIV/HCV coinfection have previously been identified with injecting drug users (IDU) as the common route of exposure.

Methods: This was cross -sectional study using HIV and HCV registries maintained by Nebraska Department of Health and Human Services (NE DHHS) from1997 to 2017. A descriptive analysis was used to characterize the sample. Chi-squared test and Fisher exact test were selected to compare the different groups. …

Health Professional Treatment Practices For Pediatric Sickle Cell Disease In Nigeria, Natalie Wichelt

Capstone Experience: Master of Public Health

Abstract

Sickle cell disease (SCD) is caused by a genetic defect that results in abnormal hemoglobin genes that can cause devastating health effects like chronic hemolytic anemia and vaso-occlusive crises. Additionally, sickle cell disease can cause defects in the immune system, leaving those with the disease highly susceptible to a variety of different infections. In the pediatric population specifically, the complications of sickle cell disease contribute significantly to the under-five mortality rate of Nigeria. In response to the Millennium Development Goals 4, 5 and 6, as well as with growing national concern over the challenges faced by sickle cell disease …