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Role Of Endothelin Axis In Pancreatic Tumor Microenvironment, Suprit Gupta

Theses & Dissertations

Endothelins (ETs) are a family of three 21 amino-acid vasoactive peptides ET-1, ET-2 and ET-3 that mediate their effects via two G-protein couple receptors ET_AR and ET_BR which are expressed on various cell types. Apart from their physiological role in vasoconstriction, there is emerging evidence supporting the role of endothelin axis (ET-axis) in cancer. Due to the expression of ET receptors on various cell-types, ET-axis can exert pleotropic effects and contribute to various aspects of cancer pathobiology. Several studies have provided a fragmented picture of the diverse roles or ET-axis in various tumors. However, the comprehensive …

Tuberculosis Contact Investigation In An Urban Omaha High School, Kyra L. Crepin

Theses & Dissertations

In November 2016, a 15-19 year old high school student was diagnosed with active pulmonary Tuberculosis (TB) and reported to the Douglas County Health Department (DCHD) in Omaha, Nebraska. A contact investigation led the health department to a local urban high school with a diverse and mobile population. A modified point of dispensing (POD) clinic was determined to be the efficient method to test the 196 faculty and students that were exposed to the index case. Emergency response coordinators (ERC’s) at DCHD adapted the POD dispensing plan with an embedded Incident Command System (ICS) to fit a smaller incident as …

Aberrant Neuronal Dynamics During Working Memory Operations In The Aging Hiv-Infected Brain., Tony W. Wilson, Amy L. Proskovec, Elizabeth Heinrichs-Graham, Jennifer O'Neill, Kevin R. Robertson, Howard S. Fox, Susan Swindells

Journal Articles: Infectious Diseases

Impairments in working memory are among the most prevalent features of HIV-associated neurocognitive disorders (HAND), yet their origins are unknown, with some studies arguing that encoding operations are disturbed and others supporting deficits in memory maintenance. The current investigation directly addresses this issue by using a dynamic mapping approach to identify when and where processing in working memory circuits degrades. HIV-infected older adults and a demographically-matched group of uninfected controls performed a verbal working memory task during magnetoencephalography (MEG). Significant oscillatory neural responses were imaged using a beamforming approach to illuminate the spatiotemporal dynamics of neuronal activity. HIV-infected patients were …

Mosquitoes Transmit Unique West Nile Virus Populations During Each Feeding Episode, Nathan D. Grubaugh, Joseph R. Fauver, Claudia Rückert, James Weger-Lucarelli, Selene Garcia-Luna, Reyes A. Murrieta, Alex Gendernalik, Darci R. Smith, Doug E. Brackney, Gregory D. Ebel

Journal Articles: Epidemiology

Arthropod-borne viruses (arboviruses), such as Zika virus, chikungunya virus, and West Nile virus (WNV), pose continuous threats to emerge and cause large epidemics. Often, these events are associated with novel virus variants optimized for local transmission that first arise as minorities within a host. Thus, the conditions that regulate the frequency of intrahost variants are important determinants of emergence. Here, we describe the dynamics of WNV genetic diversity during its transmission cycle. By temporally sampling saliva from individual mosquitoes, we demonstrate that virus populations expectorated by mosquitoes are highly diverse and unique to each feeding episode. After transmission to birds, …

Impact Of Simultaneous Exposure To Arboviruses On Infection And Transmission By Aedes Aegypti Mosquitoes, Claudia Rückert, James Weger-Lucarelli, Selene M. Garcia-Luna, Michael C. Young, Alex D. Byas, Reyes A. Murrieta, Joseph R. Fauver, Gregory D. Ebel

Journal Articles: Epidemiology

The recent emergence of both chikungunya and Zika viruses in the Americas has significantly expanded their distribution and has thus increased the possibility that individuals may become infected by more than one Aedes aegypti-borne virus at a time. Recent clinical data support an increase in the frequency of coinfection in human patients, raising the likelihood that mosquitoes could be exposed to multiple arboviruses during one feeding episode. The impact of coinfection on the ability of relevant vector species to transmit any of these viruses (that is, their vector competence) has not been determined. Thus, we here expose Ae. aegypti mosquitoes …

Without The White Coat: An Analysis Of Pathographies By Physicians With Cancer, Jonathan H. Ryder

EMET Projects

No abstract provided.

Role Of Cbl-Family Ubiquitin Ligases As Critical Negative Regulators Of T Cell Activation And Functions, Benjamin Goetz

Theses & Dissertations

Adaptive T cell immunity is essential for defense against foreign antigens and immune surveillance against cancer. Tight regulation of T cell activation is required to avoid autoimmunity to self-antigens or protracted inflammation after foreign antigens are cleared. Incomplete or inappropriate stimulation leads to an active shutdown of T cell activation called anergy. The Casitas B-lineage Lymphoma (CBL)-family of ubiquitin ligases (E3s) are essential negative regulators of T cell activation that impinge on thymic selection as well as anergy induction programs. Single gene studies show that CBL is critical during T cell development while CBL-B plays an essential role in peripheral …

Barriers To Pediatric Triage Guideline Compliance: A Survey Of Nebraska Emergency Departments, Jonathon J. Gruba

Theses & Dissertations

Nebraska emergency departments may be underprepared for a mass casualty event involving a large number of children, as indicated by the results from the 2013 Emergency Medical Services for Children’s (EMSC) Pediatric Readiness Project (PRP) report. This was primarily evident by the lack of existence of a pediatric triage policy among Nebraska emergency departments. Utilizing a survey, this study attempted to identify the emergency departments in Nebraska that followed the EMSC guideline of having a pediatric triage policy, as well as to identify possible barriers to guideline adherence among those that did not have the policy.

It was found that …

Staphylococcus Aureus Biofilms Interfere With Macrophage Antimicrobial Responses Through Differential Gene Regulation, Toxin Production, And Purine Metabolism, Tyler D. Scherr

Theses & Dissertations

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that is a leading cause of both nosocomial and community-associated infections. Armed with a myriad of virulence factors and the propensity to form a biofilm on native tissues and implanted medical devices alike, S. aureus infections represent a very real public health threat, the treatment of which results in an excessive economic burden. S. aureus biofilm infections are notoriously recalcitrant to antibiotic therapy and adept at evading and neutralizing the host immune antimicrobial response. Previous studies from our laboratory have shown that S. aureus biofilms are able to cause persistent …

Membrane-Active Epithelial Keratin 6a Fragments (Kamps) Are Unique Human Antimicrobial Peptides With A Non-Αβ Structure., Judy T.Y. Lee, Guangshun Wang, Yu Tong Tam, Connie Tam

Journal Articles: Pathology and Microbiology

Antibiotic resistance is a pressing global health problem that threatens millions of lives each year. Natural antimicrobial peptides and their synthetic derivatives, including peptoids and peptidomimetics, are promising candidates as novel antibiotics. Recently, the C-terminal glycine-rich fragments of human epithelial keratin 6A were found to have bactericidal and cytoprotective activities. Here, we used an improved 2-dimensional NMR method coupled with a new protocol for structural refinement by low temperature simulated annealing to characterize the solution structure of these kerain-derived antimicrobial peptides (KAMPs). Two specific KAMPs in complex with membrane mimicking sodium dodecyl sulfate (SDS) micelles displayed amphipathic conformations with only …

Redefining Our Territory: Reaching Pre-Matriculation Students With Case-Based, Online Instruction, Cynthia M. Schmidt, Teresa Hartman

Posters and Presentations: Leon S. McGoogan Health Sciences Library

Online educational tools have made it possible for our library to claim some educational territory that was previously unavailable to us, the pre-matriculation period. During the summer of 2015 we were able to add a two-part, case-based, online tutorial to our incoming medical students’ pre-matriculation materials. We created the story of Sarah Pilger, a hypothetical, obese, pregnant teenager whose pregnancy is complicated by a fetal toxoplasmosis. The case introduces the incoming students to almost all the resources they might want to use while enrolled at UNMC and also introduces students to the roles of the many healthcare professionals who are …

An Overview Of State Criteria For Declaring A Public Health Emergency, Fernando A. Wilson, Nizar K. Wehbi, Kavita Mosalpuria

Reports: Center for Health Policy

No abstract provided.

Evaluating Isolation Behaviors By Nurses Using Mobile Computer Workstations At The Bedside., Elizabeth L. Beam, Shawn G. Gibbs, Angela L. Hewlett, Peter C. Iwen, Suzanne L. Nuss, Philip W. Smith

Journal Articles: College of Nursing

This secondary analysis from a larger mixed methods study with a sequential explanatory design investigates the clinical challenges for nurses providing patient care, in an airborne and contact isolation room, while using a computer on wheels for medication administration in a simulated setting. Registered nurses, who regularly work in clinical care at the patient bedside, were recruited as study participants in the simulation and debriefing experience. A live volunteer acted as the standardized patient who needed assessment and intravenous pain medication. The simulation was video recorded in a typical hospital room to observe participating nurses conducting patient care in an …

Antiretroviral Therapy For The Prevention Of Hiv-1 Transmission., Myron S. Cohen, Ying Q. Chen, Marybeth Mccauley, Theresa Gamble, Mina C. Hosseinipour, Nagalingeswaran Kumarasamy, James G. Hakim, Johnstone Kumwenda, Beatriz Grinsztejn, Jose H.S. Pilotto, Sheela V. Godbole, Suwat Chariyalertsak, Breno R. Santos, Kenneth H. Mayer, Irving F. Hoffman, Susan H. Eshleman, Estelle Piwowar-Manning, Leslie Cottle, Xinyi C. Zhang, Joseph Makhema, Lisa A. Mills, Ravindre Panchia, Sharlaa Faesen, Joseph Eron, Joel Gallant, Diane Havlir, Susan Swindells, Vanessa Elharrar, David Burns, Taha E. Taha, Karin Nielsen-Saines, David D. Celentano, Max Essex, Sarah E. Hudelson, Andrew D. Redd, Thomas R. Fleming

Journal Articles: Internal Medicine

BACKGROUND: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.

METHODS: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 …

Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo

Theses & Dissertations

The introduction of nanoformulated antiretroviral therapeutic regimens is a promising alternative to standard once a day oral treatment of HIV infection. Our lab has pioneered this effort and was successful in harnessing mononuclear phagocytes (monocytes, dendritic cells and macrophages) as nanoformulated drug carriers. The approach was developed as Trojan horses for drug transport, delivery and distribution to sites of viral replication in order to facilitate microbial elimination in HIV sanctuaries. However, the remaining challenges for current antiretroviral nanoformulations include to formulate a broad range of hydrophilic short-acting drugs, and to elucidate the mechanism of sequestered nanoparticles in macrophages at the …

Assessment And Mechanisms Of Autonomic Function In Health And Disease, Peter Ricci Pellegrino

Theses & Dissertations

The autonomic nervous system is a master regulator of homeostasis, and the conviction that autonomic outflow is important on a patient-by-patient, minute-to-minute basis in both health and disease is the motivation for this thesis. The dissertation explores three aims that advance our understanding of the autonomic nervous system by elucidating the molecular mechanisms of autonomic regulation, validating widely used techniques for autonomic assessment, and developing and applying a new method to assess sympathetic vascular control.

The first aim of the dissertation was to investigate the role of the Rho kinase pathway as a mediator of the autonomic effects of central …

Aldehyde Adducts And Lung Injury, Muna Sapkota

Theses & Dissertations

From the time of discovery, people have used both alcohol and tobacco in various forms all around the world. Alcohol abuse and cigarette smoking causes thousands of preventable deaths in the US each year. Several lung diseases such as COPD, asthma, respiratory infections, pneumonia, acute respiratory distress syndrome, cancer of neck, throat, mouth and lung are associated with smoking and drinking. Even though some studies have examined the role of alcohol and cigarette smoke in lung diseases, only a few studies have focused on the role of reactive aldehydes generated in the lungs of those who abuse alcohol and smoke …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher

Theses & Dissertations

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream …

A Survey Of Tuberculosis Infection Control Practices At The Nih/Niaid/Daids-Supported Clinical Trial Sites In Low And Middle Income Countries., Catherine Godfrey, Gail Tauscher, Sally Hunsberger, Melissa Austin, Lesley Scott, Jeffrey T. Schouten, Anne F. Luetkemeyer, Constance Benson, Robert Coombs, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement.

METHODS: A survey was developed that assessed IC activities in three domains: facility …

Establishment Of Comprehensive Training Center In Tajikistan, Umeda Sadykova

Theses & Dissertations

There is a notable increase in the number of natural and manmade disasters all over the world in the past two decades. Emergency preparedness is a field that is drawing increased attention in many countries. Tajikistan is a disaster prone country with unforgiving nature and weak preparedness infrastructure/system. Tajikistan’s weak emergency preparedness system can be attributed to two main reasons; lack of coordination between the government and international emergency organizations, and the paucity of well trained and organized network of emergency professionals. This study drafted a proposal to establish a comprehensive training center in Tajikistan. This training center will be …

Using Homeland Security Exercise Evaluation Program To Execute A Mass Prophylaxis Exercise In A Rural Community., Brian K. Smith

Theses & Dissertations

This project explores the execution of point of distribution exercises in a rural community. Harrison County Iowa is a rural county with a population over 15,000 located approximately 45 minutes north of the Omaha metro area. The project explored the existing point of distribution plans and inventory for the Harrison County Home and Public Health Department. Prior to this project, many staff at Harrison County Home and Public Health Department had no experience with table top or full scale exercises. The mass prophylaxis point of distribution plan had not been updated, and staff had not received training on the point …

Defining The Role Of Interferon Regulatory Factor 4 In Chronic Lymphocytic Leukemia., Vipul Shukla

Theses & Dissertations

Chronic Lymphocytic Leukemia (CLL) represents the most common adult leukemia in the Western hemisphere. Despite considerable progress in our current understanding of CLL, this disease remains incurable and the molecular events underlying the complex pathogenesis of CLL are not fully elucidated. Interferon Regulatory Factor 4 (IRF4) belongs to the IRF superfamily of transcription factors that has been shown to play critical roles at multiple stages of B cell development. Interestingly, a Genome Wide Association Study identified Single Nucleotide Polymorphism (SNP) mediated IRF4 down regulation, as a major predisposing genetic event during the development of CLL. However, whether low levels of …

Exploring Emergency Communication Experiences In Response To The 2010 Haiti Earthquake: Lessons Learned From International Donors And Local Government Agencies, Pierre Marie Barbara Roussel

Theses & Dissertations

Background:

In almost every disaster situation, the use of standardized communication procedures among humanitarian relief agencies has been identified as one of the efficient practices to minimize the mismanagement of resources and thus to maximize the response effort among actors to reduce the incidence impact on the public and to increase their resilience capabilities.

Agencies have access to several guidelines to follow during domestic disasters, but there have been very few manuals developed to guide relief organizations on best practices during international large and complex natural disasters such as the 2010 Haiti earthquake.

Haiti has experienced over its history several …

Physical Activity Levels And Related Factors In Midwestern Rural Hispanic Or Latino Adults, Alison K. Clevette

Theses & Dissertations

The purpose of this dissertation was to examine physical activity levels and specific intrapersonal, interpersonal and community physical environment factors that influence physical activity in Midwestern rural Hispanic or Latino adults. Instruments used in the study included: Self-Efficacy for Exercise Behaviors Survey, Social Support for Exercise Survey, Short Acculturation Scale for Hispanics (SASH), and Neighborhood Environment Walkability Scale (NEWS). Physical activity was measured by 7-Day Physical Activity Recall and ActiGraph^® accelerometer data. In the study of 54 participants, it was found that there was a very low level of physical activity. For example, 97% of the time was spent …

A New Genotype Of Bovine Leukemia Virus In South America Identified By Ngs-Based Whole Genome Sequencing And Molecular Evolutionary Genetic Analysis., Meripet Polat, Shin-Nosuke Takeshima, Kazuyoshi Hosomichi, Jiyun Kim, Taku Miyasaka, Kazunori Yamada, Mariluz Araínga, Tomoyuki Murakami, Yuki Matsumoto, Veronica De La Barra Diaz, Carlos J. Panei, Ester T. González, Misao Kanemaki, Misao Onuma, Guillermo Giovambattista, Yoko Aida

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Bovine leukemia virus (BLV) is a member of retroviridae family, together with human T cell leukemia virus types 1 and 2 (HTLV-1 and -2) belonging to the genes deltaretrovirus, and infects cattle worldwide. Previous studies have classified the env sequences of BLV provirus from different geographic locations into eight genetic groups. To investigate the genetic variability of BLV in South America, we performed phylogenetic analyses of whole genome and partial env gp51 sequences of BLV strains isolated from Peru, Paraguay and Bolivia, for which no the molecular characteristics of BLV have previously been published, and discovered a novel BLV …

Exome Screening To Identify Loss-Of-Function Mutations In The Rhesus Macaque For Development Of Preclinical Models Of Human Disease, Adam Cornish, Robert M. Gibbs, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Exome sequencing has been utilized to identify genetic variants associated with disease in humans. Identification of loss-of-function mutations with exome sequencing in rhesus macaques (Macaca mulatta) could lead to valuable animal models of genetic disease. Attempts have been made to identify variants in rhesus macaques by aligning exome data against the rheMac2 draft genome. However, such efforts have been impaired due to the incompleteness and annotation errors associated with rheMac2. We wished to determine whether aligning exome reads against our new, improved rhesus genome, MacaM, could be used to identify high impact, loss-of-function mutations in rhesus macaques that would …

Factors Underlying Ebola Virus Infection Among Health Workers, Kenema, Sierra Leone, 2014-2015, Mikiko Senga, Kimberly Pringle, Andrew Ramsay, David Brett-Major, Robert A. Fowler, Issa French, Mohamed Vandi, Josephine Sellu, Christian Pratt, Josephine Saidu, Nahoko Shindo, Daniel G. Bausch, Sierra Leone Kenema District Task Force And Kenema Government Hospital

Journal Articles: Epidemiology

BACKGROUND: Ebola virus disease (EVD) in health workers (HWs) has been a major challenge during the 2014-2015 outbreak. We examined factors associated with Ebola virus exposure and mortality in HWs in Kenema District, Sierra Leone.

METHODS: We analyzed data from the Sierra Leone National Viral Hemorrhagic Fever Database, contact tracing records, Kenema Government Hospital (KGH) staff and Ebola Treatment Unit (ETU) rosters, and burial logs.

RESULTS: From May 2014 through January 2015, 600 cases of EVD originated in Kenema District, including 92 (15%) HWs, 66 (72%) of whom worked at KGH. Among KGH medical staff and international volunteers, 18 of …

West African Anopheles Gambiae Mosquitoes Harbor A Taxonomically Diverse Virome Including New Insect-Specific Flaviviruses, Mononegaviruses, And Totiviruses, Joseph R. Fauver, Nathan D. Grubaugh, Benjamin J. Krajacich, James Weger-Lucarelli, Steven M. Lakin, Lawrence S. Fakoli, Fatorma K. Bolay, Joseph W. Diclaro, Kounbobr Roch Dabiré, Brian D. Foy, Doug E. Brackney, Gregory D. Ebel, Mark D. Stenglein

Journal Articles: Epidemiology

Anopheles gambiae are a major vector of malaria in sub-Saharan Africa. Viruses that naturally infect these mosquitoes may impact their physiology and ability to transmit pathogens. We therefore used metagenomics sequencing to search for viruses in adult Anopheles mosquitoes collected from Liberia, Senegal, and Burkina Faso. We identified a number of virus and virus-like sequences from mosquito midgut contents, including 14 coding-complete genome segments and 26 partial sequences. The coding-complete sequences define new viruses in the order Mononegavirales, and the families Flaviviridae, and Totiviridae. The identification of a flavivirus infecting Anopheles mosquitoes broadens our understanding of the evolution and host …

Clinical Profile And Containment Of The Ebola Virus Disease Outbreak In Two Large West African Cities, Nigeria, July-September 2014, Chima Ohuabunwo, Celestine Ameh, Oyin Oduyebo, Anthony Ahumibe, Bamidele Mutiu, Adebola Olayinka, Wasiu Gbadamosi, Erika Garcia, Carolina Nanclares, Wale Famiyesin, Abdulaziz Mohammed, Patrick Nguku, Richard I. Koko, Joshua Obasanya, Durojaye Adebayo, Yemi Gbadegesin, Oni Idigbe, Olukayode Oguntimehin, Sara Nyanti, Charles Nzuki, Ismail Abdus-Salam, Joseph Adeyemi, Nnanna Onyekwere, Emmanuel Musa, David Brett-Major, Faisal Shuaib, Abdulsalami Nasidi

Journal Articles: Epidemiology

INTRODUCTION: The Ebola virus disease (EVD) outbreak in Nigeria began when an infected diplomat from Liberia arrived in Lagos, the most populous city in Africa, with subsequent transmission to another large city.

METHODS: First-, second-, and third-generation contacts were traced, monitored, and classified. Symptomatic contacts were managed at Ebola treatment centers as suspected, probable, and confirmed EVD cases using standard operating procedures adapted from the World Health Organization EVD guidelines. Reverse transcription PCR tests confirmed EVD. Socio-demographic, clinical, hospitalization, and outcome data of the July-September 2014 Nigeria EVD cohort were analyzed.

RESULTS: The median age of the 20 EVD cases …