Persistent Low-Level Replication Of Sivδnef Drives Maturation Of Antibody And Cd8 T Cell Responses To Induce Protective Immunity Against Vaginal Siv Infection, Sama Adnan, R. Keith Reeves, Jacqueline Gillis, Fay E. Wong, Yi Yu, Jeremy V. Camp, Qingsheng Li, Michelle Connole, Yuan Li, Michael Piatak Jr., Jeffrey D. Lifson, Wenjun Li, Brandon F. Keele, Pamela A. Kozlowski, Ronald C. Desrosiers, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef …

Comparing Short Versus Long Term Antibiotics For Reducing Persistent Lyme Symptoms, Joe Webster

Physician Assistant Scholarly Project Posters

• Lyme disease is the most common tick borne illness in the United States with over 300,000 cases annually.

• Two main organizations called the Infectious Disease Society of America and the International Lyme and Associated Diseases Society differ on their opinions in the treatment duration of Lyme disease.

• A review of the literature explored studies that compared the effectiveness of short term versus long term antibiotics in the treatment of Lyme. Determining the most effective treatment method duration for reducing the long term risk of persistent symptoms of Lyme will be important for the improvement of the delivery …

Typical Hus: Evidence Of Acute Phase Complement Activation From A Daycare Outbreak, T M. Brady, C Pruette, L F. Loeffler, Darcy Weidemann, J J. Strouse, E Gavriilaki, R A. Brodsky

Manuscripts, Articles, Book Chapters and Other Papers

The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by …

Reducing Overutilization Of Testing For Clostridium Difficile Infection In A Pediatric Hospital System: A Quality Improvement Initiative., J Michael Klatte, Rangaraj Selvarangan, Mary Anne Jackson, Angela Myers

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Study objectives included addressing overuse of Clostridium difficile laboratory testing by decreasing submission rates of nondiarrheal stool specimens and specimens from children ≤12 months of age and determining resultant patient and laboratory cost savings associated with decreased testing.

METHODS: A multifaceted initiative was developed, and components included multiple provider education methods, computerized order entry modifications, and automatic declination from laboratory on testing stool specimens of nondiarrheal consistency and from children ≤12 months old. A run chart, demonstrating numbers of nondiarrheal plus infant stool specimens submitted over time, was developed to analyze the initiative's impact on clinicians' test-ordering practices. A …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Complete Genome Sequence Of Highly Virulent Porcine Reproductive And Respiratory Syndrome Virus Variants That Recently Emerged In The United States, Aspen M. Workman, Timothy P.L. Smith, Fernando A. Osorio, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

A recent outbreak of particularly virulent disease caused by porcine reproductive and respiratory syndrome virus has occurred in swine herds across the United States. We report here the complete genome sequence of eight viral isolates from four Nebraska herds experiencing an outbreak of severe disease in 2016.

Kaposi’S Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (Myd88) Expression Via Modulation Of Its Rna, Amy Lingel, Erica Ehlers, Qianli Wang, Mingxia Cao, Charles Wood, Rongtuan Lin, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of …

Domain I Of The 5′ Non-Translated Genomic Region In Coxsackievirus B3 Rna Is Not Required For Productive Replication, L. Jaramillo, S. Smithee, S. Tracy, N. M. Chapman

Nebraska Center for Virology: Faculty Publications

Domain I is a cloverleaf-like secondary structure at the 5′ termini of all enterovirus genomes, comprising part of a cis-acting replication element essential for efficient enteroviral replication. 5′ genomic terminal deletions up to as much as 55% of domain I can occur without lethality following coxsackie B virus infections. We report here that the entire CVB structural domain I can be deleted without lethality.

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Head-to-head comparisons of conventional influenza vaccines with ade- novirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we de- veloped “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than …

Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5- fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. …

Slug Bug: Quality Improvement With Orchestrated Testing Leads To Nicu Clabsi Reduction., Anthony J. Piazza, Beverly Brozanski, Lloyd Provost, Theresa R. Grover, John Chuo, Joan R. Smith, Teresa Mingrone, Susan Moran, Lorna Morelli, Isabella Zaniletti, Eugenia K. Pallotto

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Reduce central line-associated bloodstream infection (CLABSI) rates 15% over 12 months in children's hospital NICUs. Use orchestrated testing as an approach to identify important CLABSI prevention practices.

METHODS: Literature review, expert opinion, and benchmarking were used to develop clinical practice recommendations for central line care. Four existing CLABSI prevention strategies (tubing change technique, hub care monitoring, central venous catheter access limitation, and central venous catheter removal monitoring) were identified for study. We compared the change in CLABSI rates from baseline throughout the study period in 17 participating centers. Using orchestrated testing, centers were then placed into 1 of 8 …

A Healthy Herd: Addressing The Justifications For Vaccine Denial And Applying The Health Belief Model To The Current Anti-Vaccination Movement, Sarah L. Mchugh

Honors Program Theses

The purpose of this thesis is to explore and analyze the existing literature regarding the refusal to receive vaccinations designed specifically to prevent Measles-Mumps-Rubella (MMR), which has spurred a serious public health issue that puts every unvaccinated person at risk. It will investigate the reasons people refuse to get vaccinations for themselves or their children. The analysis of the current situation and the application of the Health Belief Model to the related factors will provide potential explanations regarding how the decision-making process may strengthen efforts towards increasing vaccination rates.

Hiv/Aids Care And Prevention Infrastructure In The U.S. Deep South, Susan S. Reif, Kristen Sullivan, Elena Wilson, Miriam Berger, Carolyn Mcallaster

Faculty Scholarship

No abstract provided.

We Have The Tools To End Hiv: Benefits, Barriers, And Solutions To Expanded Utilization Of Pre-Exposure Prophylaxis (Prep) In The Us Deep South, Jason Ervin, Allison Weller Tikare, Carolyn Mcallaster

Faculty Scholarship

No abstract provided.

The Effectiveness Of Antibiotic Treatment In Lyme Neuroborreliosis, Lane Lindeman

Physician Assistant Scholarly Project Posters

• Lyme disease is caused by human infection with Borrelia burgdorferi, a spirochete transmitted by the Ixodes tick which is indigenous primarily to an increasingly large area of the Northeast and Midwest United States.

• Manifestations of Lyme disease vary greatly, and can result in significant neurologic symptoms associated with complications of neuroborreliosis or neurologic Lyme disease.

• Diagnosis and treatment of Lyme disease and its complications has been a source of debate and confusion for providers and patients alike.

• The purpose of this study was to investigate the effectiveness and efficacy of antibiotic therapy in patients with symptoms …

Facilitating Hiv Pre-Exposure Prophylaxis (Prep) Familiarity Among Vermont Primary Care Providers, Michael Ohkura

Family Medicine Clerkship Student Projects

Please see the updated version of this presentation: Ohkura, Michael; Bonefant, Nicholas; and Upton, Michael D., "A Sex-Positive Approach to Healthcare, and Truvada as HIV Pre-Exposure Prophylaxis (PrEP)" (2018). College of Medicine Faculty Publications. 3. https://scholarworks.uvm.edu/comfac/3

Nationally, incidence of new HIV infections has hovered around over 50,000 per year and men who have sex with men (MSM) carry the largest burden. In Vermont, 56% of individuals newly diagnosed are MSM, with 25% of diagnoses among youth ages 13-24 years old. Despite the proven efficacy and approval of daily Truvada (emtricitabine + tenofovir) as Pre-Exposure Prophylaxis (PrEP) against HIV infection, …

Putting Prep Into Practice: Lessons Learned From Early-Adopting U.S. Providers’ Firsthand Experiences Providing Hiv Pre-Exposure Prophylaxis And Associated Care, Sarah K. Calabrese, Manya Magnus, Kenneth H. Mayer, Douglas S. Krakower, Adam I. Eldahan, Lauren A. Gaston Hawkins, Nathan B. Hansen, Trace S. Kershaw, Kristen Underhill, Joseph R. Betancourt, John F. Dovidio

Faculty Scholarship

Optimizing access to HIV pre-exposure prophylaxis (PrEP), an evidence-based HIV prevention resource, requires expanding healthcare providers’ adoption of PrEP into clinical practice. This qualitative study explored PrEP providers’ firsthand experiences relative to six commonly-cited barriers to prescription – financial coverage, implementation logistics, eligibility determination, adherence concerns, side effects, and anticipated behavior change (risk compensation) – as well as their recommendations for training PrEP-inexperienced providers. U.S.-based PrEP providers were recruited via direct outreach and referral from colleagues and other participants (2014-2015). One-on-one interviews were conducted in person or by phone, transcribed, and analyzed. The sample (n = 18) primarily practiced …

Effect Of Mobile Phone Text Messages Reminders On Uptake Of Routine Immunization Among Children In Pakistan- Study Protocol For A Randomized Clinical Trial, Abdul Momin Kazi, Murtaza Ali, Khurram Zubair, Hussain Kalimuddin, Syed Asad Ali

Department of Paediatrics and Child Health

Introduction: Routine Immunization (RI) is considered one of the best public health interventions to decrease child morbidity and mortality. The RI coverage in Pakistan is still well below the desired level, leading to continued polio transmission, large measles outbreaks and thousands of deaths from vaccine-preventable illnesses. Different innovative and cost effective strategies are required to look into for enhancement in vaccination uptake and coverage. We plan to test the effectiveness of reminders to parents/caregivers on cell phones through short messaging system (SMS) in improving vaccine uptake and on-time routine immunization for children in Pakistan.
Methods and Analysis: A parallel-randomized controlled …

How N.Y.’S Biggest For-Profit Nursing Home Group Flourishes Despite A Record Of Patient Harm, Jennifer Lehman

Capstones

How N.Y.'s Biggest For-Profit Nursing Home Group Flourishes Despite a Record of Patient Harm

The state’s “character-and-competence” reviews are supposed to weed out operators with histories of violations and fines— but regulators don’t always act on the full story.

Dysregulation Of The Haem-Haemopexin Axis Is Associated With Severe Malaria In A Case-Control Study Of Ugandan Children., Robyn E Elphinstone, Frank Riley, Tian Lin, Sarah Higgins, Aggrey Dhabangi, Charles Musoke, Christine Cserti-Gazdewich, Raymond F. Regan, H Shaw Warren, Kevin C Kain

Department of Medicine Faculty Papers

BACKGROUND: Malaria is associated with haemolysis and the release of plasma haem. Plasma haem can cause endothelial injury and organ dysfunction, and is normally scavenged by haemopexin to limit toxicity. It was hypothesized that dysregulation of the haem-haemopexin pathway contributes to severe and fatal malaria infections.

METHODS: Plasma levels of haemin (oxidized haem), haemopexin, haptoglobin, and haemoglobin were quantified in a case-control study of Ugandan children with Plasmodium falciparum malaria. Levels at presentation were compared in children with uncomplicated malaria (UM; n = 29), severe malarial anaemia (SMA; n = 27) or cerebral malaria (CM; n = 31), and evaluated …