Digital Commons Network^™

Genetic Barrier To Direct Acting Antivirals In Hcv Sequences Deposited In The European Databank, Dimas Alexandre Kliemann, Cristiane Valle Tovo, Ana Beatriz Gorini Da Veiga, André Luiz Machado, John T. West

Nebraska Center for Virology: Faculty Publications

Background & Aims: Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs.

Methods: The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzed 789 NS3 sequences, 708 sequences and 536 NS5B …

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 …

Nf45 And Nf90 Bind Hiv-1 Rna And Modulate Hiv Gene Expression, Yan Li, Michael Belshan

Nebraska Center for Virology: Faculty Publications

A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 …

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. …

Cutaneous Human Papillomavirus Infection And Development Of Subsequent Squamous Cell Carcinoma Of The Skin, Shalaka S. Hampras, Rhianna A. Reed, Spencer Bezalel, Michael Cameron, Basil Cherpelis, Neil Fenske, Vernon K. Sondak, Jane Messina, Massimo Tommasino, Tarik Gheit, Dana E. Rollison

Pathology and Cell Biology Faculty Publications

The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC () enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations …

Doctor Of Osteopathic Medicine Curriculum, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Pyoderma Gangrenosum Following Bilateral Deep Inferior Epigastric Perforator Flaps, Eric Clayman, Kristen Marcet, Lauren Kuykendall, Dunya M. Atisha

Surgery Faculty Publications

Pyoderma gangrenosum (PG) is an atypical ulcerative cutaneous condition, with an estimated six cases per million people per year in the United States.[1] One-half of patients have idiopathic disease, and it is most commonly associated with underlying systemic inflammatory conditions or hematologic malignancies.[1] [2] There have been several reported cases of PG following breast reduction procedures; however, postsurgical PG (PSPG) is rarely seen following autologous tissue breast reconstruction.[3]

In this article, the authors report the clinical course, treatment, and outcome of a patient diagnosed with PSPG following a delayed breast reconstruction with …

Reference Intervals For Thyroid Stimulating Hormone And Free Thyroxine Derived From Neonates Undergoing Routine Screening For Congenital Hypothyroidism At A University Teaching Hospital In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Ali Kassim, Francis Kiigu, Syeda Hussain, Mary Limbe

Pathology, East Africa

Background: In order to accurately interpret neonatal thyroid function tests (TFTs), it is necessary to have population specific reference intervals (RIs) as there is significant variation across different populations possibly due to genetic, environmental or analytical issues. Despite the importance of RIs, globally there are very few publications on RIs for neonatal TFTs primarily due to ethical and technical issues surrounding recruitment of neonates for a prospective study. To the best of our knowledge, this is the first report from Africa on neonatal RIs for TFTs.

Methods: We used hospital based data largely derived from neonates attending the wellness clinic …

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 …

A Dramaturgical Analysis Of The Miracle Worker, Abby Butzer

All Graduate Theses, Dissertations, and Other Capstone Projects

This document is a thesis submitted in partial fulfillment of the Master of Arts degree in theatre. It is a dramaturgical analysis for William Gibson's play The Miracle Worker, providing a reference for directors and actors. The thesis explores the play's medical and pedagogical history in six chapters: the physiology and psychology of language acquisition as it pertains to sight and/or hearing impaired children, a pedagogical comparison of Samuel G. Howe and Annie Sullivan, a modern diagnosis of the fever that destroyed Helen Keller's vision and hearing, the 19th century pathology and treatment options for the disease of the eye …

The Role Of Capillaries In The Lesser Ailments Of Old Age And In Alzheimer's Disease And Vascular Dementia: The Potential Of Pro-Therapeutic Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and …

Recapitulating Cross-Species Transmission Of Sivcpz To Humans Using Humanized-Blt Mice, Zhe Yuan, Guobin Kang, Fangrui Ma, Wuxun Lu, Wenjin Fan, Christine M. Fennessey, Brandon F. Keele, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The origins of HIV-1 have been widely accepted to be the consequence of simian immunodeficiency viruses from wild chimpanzees (SIVcpz) crossing over to humans. However, there has not been any in vivo study of SIVcpz infection of humans. Also, it remains largely unknown why only specific SIVcpz strains have achieved cross-species transmission and what transmission risk might exist for those SIVcpz strains that have not been found to infect humans. Closing this knowledge gap is essential for better understanding cross-species transmission and predicting the likelihood of additional cross-species transmissions of SIV into humans. Here we show hu-BLT mice are susceptible …

High Glucose Induces Reactivation Of Latent Kaposi’S Sarcoma-Associated Herpesvirus, Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou-Jiang Gao

Nebraska Center for Virology: Faculty Publications

High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29

grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high …

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 …

Digest Of The Philadelphia College Of Osteopathic Medicine (Winter 2015-2016), Philadelphia College Of Osteopathic Medicine

Digest

The Winter 2015/2016 issue of the Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Message from the President
• PCOM Updates
• Inauguration of the eighth President, Jay S. Feldstein, DO '81
• Trained for Trauma Care: PCOM Alumni Were Well Prepared to Treat the Mass Casualties of May's Amtrak Derailment
• Remembering Camille DiLullo, PhD, Professor of Anatomy
• Class Notes
• My Turn

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.

Disaster Preparedness And Response: A Survey Of U.S. Dental Hygienists, Brenda T. Bradshaw, Ann P. Bruhn, Tara L. Newcomb, Bridget T. Giles, Kathryn Simms

Dental Hygiene Faculty Publications

Purpose: The purpose of this study was to assess dental hygienists’ interests, current involvement, formal education, views, comfort levels, and intentions for involvement with disaster preparedness and response.

Methods: Dental hygienists (n=400) were asked to respond to a 21-item online survey. Data was analyzed using descriptive statistics, chi-square goodness-of-fit tests, and a paired-samples t-test. Common themes were identified and categorized from open-ended questions.

Results: A response rate of 84% (n=334) was obtained. Most respondents (97%) reported no involvement with disaster preparedness and response; however, a majority (86%) reported interest. Of those who indicated an interest in disaster preparedness and response, …

Evidence And Evidence Gaps In Adolescent Health, George Patton, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

The momentum to bring adolescents and young adults to center stage in global health and international development is palpable. Adolescents are increasingly seen as a crucial group for the success of the newly adopted Agenda for Sustainable Development [1]. Sitting within the Agenda for Sustainable Development framework, the 2030 Global Strategy for Women's, Children's and Adolescents' Health has extended the Every Woman, Every Child agenda to adolescence [2]. The strategy articulates the need for adolescent responsive health systems as well as social determinants, a focus that extends to legal and policy environments [3]. Countries seeking to adopt this more holistic …

Selective Induced Altered Coccidians To Immunize And Prevent Enteritis, Helieh S. Oz

Physiology Faculty Publications

Microbiomic flora in digestive tract is pivotal to the state of our health and disease. Antibiotics affect GI, control composition of microbiome, and shift equilibrium from health into disease status. Coccidiosis causes gastrointestinal inflammation. Antibiotic additives contaminate animal products and enter food chain, consumed by humans with possible allergic, antibiotic resistance and enigmatic side effects. Purposed study induced nonpathogenic, immunogenic organisms to protect against disease and abolish antibiotics’ use in food animals and side effects in man. Diverse species of Coccidia were used as model. Immature organisms were treated with serial purification procedure prior to developmental stages to obtain altered …

Vitamin D Levels In Black African Adults At The Aga Khan University Hospital Nairobi, Elizabeth Muringa Kagotho

Master of Medicine in Clinical Pathology

Introduction: Vitamin D has been known for centuries for its benefits in bone health. Recent observational studies have however demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults. The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few and have shown that vitamin D deficiency ranges from 5-91%. In view of the difference in skin colour, …

Intrahepatic Cholestasis Of Pregnancy With Severe Elevation Of Bile Acids In The Setting Of Acute Hepatitis C Infection, Megan L. Lawlor, Agatha S. Critchfield

Obstetrics and Gynecology Faculty Publications

Intrahepatic cholestasis of pregnancy (ICP) is a complication of pregnancy resulting in elevation of serum bile acid levels. ICP is often associated with underlying liver disease, including hepatitis C. Bile acids in relationship to the acute infection of hepatitis C virus have not yet been delineated in the literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin gestation and history of intravenous drug abuse developed ICP in the setting of acute hepatitis C infection. In addition to clinical symptoms of pruritus and right upper quadrant pain, she developed severe elevation in bile acids, 239 micromol/L, and transaminitis aspartate …

World Allergy Organization-Mcmaster University Guidelines For Allergic Disease Prevention (Glad-P): Prebiotics., Carlos A. Cuello-Garcia, Alessandro Fiocchi, Ruby Pawankar, Juan José Yepes-Nuñez, Gian Paolo Morgano, Yuan Zhang, Kangmo Ahn, Suleiman Al-Hammadi, Arnav Agarwal, Shreyas Gandhi, Kirsten Beyer, Wesley Burks, Giorgio W. Canonica, Motohiro Ebisawa, Rose Kamenwa, Bee Wah Lee, Haiqi Li, Susan Prescott, Lanny Rosenwasser, Hugh Sampson, Michael Spigler, Luigi Terracciano, Andrea Vereda, Susan Waserman, Holger J. Schünemann, Jan L. Brożek

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10 % and reaches 20-30 % in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Prebiotics - non-digestible oligosaccharides that stimulate growth of probiotic bacteria - have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.

OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of prebiotics in the prevention of allergy. …

Racemose Neurocysticercosis., Kristin Krupa, Kelly Krupa, Bs, Mary L Pisculli, Deena M Athas, Christopher J Farrell, Md

Department of Neurosurgery Faculty Papers

BACKGROUND: Neurocysticercosis (NCC) is an invasive parasitic infection of the central nervous system caused by the larval stage of the tapeworm Taenia solium. The clinical manifestations of NCC depend on the parasitic load and location of infection, as well as the developmental stage of the cysticerci and host immune response, with symptoms ranging from subclinical headaches to seizures, cerebrovascular events, and life-threatening hydrocephalus. Racemose NCC represents a particularly severe variant of extraparenchymal NCC characterized by the presence of multiple confluent cysts within the subarachnoid space and is associated with increased morbidity and mortality, as well as a decreased response to …

"I Always Worry About What Might Happen Ahead" : Implementing Safer Conception Services In The Current Environment Of Reproductive Counseling For Hiv-Affected Men And Women In Uganda, Lynn T. Matthews, Francis Bajunirwe, Jasmine Kastner, Naomi Sanyu, Cecilia Akatukwasa, Courtney Ng, Rachel Rifkin, Cecilia Milford, Lizzie Moore, Ira B. Wilson, David Bangsberg, Jennifer A. Smit, Angela Kaida

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background. We explored healthcare provider perspectives and practices regarding safer conception counseling for HIV-affected clients. Methods.We conducted semistructured interviews with 38 providers (medical and clinical officers, nurses, peer counselors, and village health workers) delivering care to HIV-infected clients across 5 healthcare centres in Mbarara District, Uganda. Interview transcripts were analyzed using content analysis. Results. Of 38 providers, 76% were women with median age 34 years (range 24–57). First, we discuss providers’ reproductive counseling practices. Emergent themes include that providers (1) assess reproductive goals of HIV-infected female clients frequently, but infrequently for male clients; (2) offer counseling focused on “family planning” …

Naegleria Fowleri Meningoencephalitis Associated With Public Water Supply, Pakistan, 2014, Najia Ghanchi, Erum Khan, Azam Khan, Wali Muhammad, Faisal Riaz Malik, Afia Zafar

Department of Pathology and Laboratory Medicine

No abstract provided.

Primary Healthcare Policy Implementation In South Asia, Chris Van Weel, Ryuki Kassai, Waris Qidwai, Raman Kumar, Kanu Bala, Pramendra Prasad Gupta, Ruvaiz Haniffa Haniffa, Neelamani Rajapaksa Hewageegana, Thusara Ranasinghe, Michael Kidd, Amanda Howe

Department of Family Medicine

Primary healthcare is considered an essential feature of health systems to secure population health and contain costs of healthcare while universal health coverage forms a key to secure access to care. This paper is based on a workshop at the 2016 World Organization of Family Doctors (WONCA) South Asia regional conference, where the health systems of Bangladesh, India, Nepal, Pakistan and Sri Lanka were presented in relation to their provision of primary healthcare. The five countries have in recent years improved the health of their populations, but currently face the challenges of non-communicable diseases and ageing populations. Primary healthcare should …

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.

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.

Reversion To Wildtype Of A Mutated And Nonfunctional Coxsackievirus B3cre(2c), Shane Smithee, Steven Tracy, Nora M. Chapman

Nebraska Center for Virology: Faculty Publications

The cis-acting replication element (CRE) in the 2C protein coding region [CRE(2C)] of enteroviruses (EV) facilitates the addition of two uridine residues (uridylylation) onto the virus-encoded protein VPg inorder for it to serve as the RNA replication primer. We demonstrated that coxsackievirus B3 (CVB3) is replication competent in the absence of a native (uridylylating) CRE(2C) and also demonstrated that lackof a functional CRE(2C) led to generation of 5’ terminal genomic deletions in the CVB3 CRE-knock-out (CVB3-CKO) population. We asked whether reversion of the mutated CRE(2C) occurred, thus permitting sustained replication, and when were 5’ terminal deletions generated during replication. Virions …

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 …