Diseases Commons^™

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

A Cysteine Zipper Stabilizes A Pre-Fusion F Glycoprotein Vaccine For Respiratory Syncytial Virus, Guillaume B. E. Stewart-Jones, Paul V. Thomas, Man Chen, Aliaksandr Druz, Gordon M. Joyce, Wing-Pui Kong, Mallika Sastry, Conque Soto, Yongping Yang, Baoshan Zhang, Lei Chen, Gwo-Yu Chuang, Ivelin S. Georgiev, Jason S. Mclellan

Dartmouth Scholarship

Recombinant subunit vaccines should contain minimal non-pathogen motifs to reduce potential off-target reactivity. We recently developed a vaccine antigen against respiratory syncytial virus (RSV), which comprised the fusion (F) glycoprotein stabilized in its pre-fusion trimeric conformation by “DS-Cav1” mutations and by an appended C-terminal trimerization motif or “foldon” from T4-bacteriophage fibritin. Here we investigate the creation of a cyste- ine zipper to allow for the removal of the phage foldon, while maintaining the immunogenic- ity of the parent DS-Cav1+foldon antigen. Constructs without foldon yielded RSV F monomers, and enzymatic removal of the phage foldon from pre-fusion F trimers resulted in …

Middle East Respiratory Syndrome: A Global Health Challenge, Lawrence O. Gostin, Daniel Lucey

Georgetown Law Faculty Publications and Other Works

Beginning in May 2015, Middle-East respiratory syndrome (MERS) experienced its first publicly reported “super-spreading” event in South Korea. By mid-June, more than 120 cases and 11 deaths in South Korea had been linked to a businessman returning from travel to Bahrain, United Arab Emirates, the Kingdom of Saudi Arabia and Qatar. Globally more than 1200 had been infected of whom more than 450 died—a high fatality rate of 37%.

What are the most effective legal, social, and public health responses to MERS and other emerging diseases? First, the World Health Organization’s International Health Regulations (IHR) did not effectively guide the …

Know Your Status: Alleviating Stigma From The Hiv Positive Community Of San Luis Obispo California, Mario Alberto Viveros Espinoza

Ethnic Studies

The purpose of this project is to alleviate stigma from the HIV community in San Luis Obispo, CA by creating an outreach program, “Know Your Status,” that raises awareness of HIV education and prevention. Research on HIV stigma and on ideologies for program development and implementation shows that HIV positive individuals face both internalized and externalized stigma. Program development and implementation can be effective by assessing and addressing the specific needs of those living within the community. This project includes the data needed for program development and implementation, collected through anonymous surveys from HIV positive community members, interviews with professionals …

Accelerating The Dual Elimination Of Mother‐To‐Child Transmission Of Syphilis And Hiv: Why Now?, James Kiarie, Chandra K. Mishra, Marleen Temmerman, Lori Newman

Obstetrics and Gynaecology, East Africa

Even though the elimination of congenital syphilis has been on the maternal and child health (MCH) agenda for over a decade, elimination has not yet been achieved; what, then, are the factors currently facilitating the elimination of mother-to-child transmission (MTCT) of syphilis?

Preliminary Evaluation Of The Disease Surveillance System During Influenza Outbreaks Of Pandemic Scale, Eric Meisheri, Diana M. Prieto, Peter Holvenstot, Richard Vanenk

Frontiers in Public Health Services and Systems Research

In the United States it is currently unknown whether the influenza surveillance system is capable of producing timely and accurate data for case estimation during an outbreak of pandemic scale. This simulation provides a preliminary evaluation of the surveillance system’s ability to collect data and produce timely and accurate trends of cases confirmed with an influenza virus. For the evaluation, a computer-based simulation of the data-collection process was used, which was validated with real demographic and epidemiologic information. The results were analyzed to determine the most significant behavioral and operational factors influencing the data collection and to propose the exploration …

Effect Of Cmvil-10 On Exosome Production By Human Breast Cancer Cells, Susanna N. Basappa

Undergraduate Honors Theses

Human cytomegalovirus (HCMV) is a ubiquitous virus that infects 70-90% of the general population, primarily the immunocompromised, but has been implicated in several forms of cancer, including breast cancer. Breast cancer is the second leading cause of cancer related deaths in women in North America, usually from metastasis. Exosomes are 30-100nm vesicles produced by most cells which carry protein and RNA to cells in their microenvironment. The aim of this study is to investigate the impact of HCMV-infection of a secreted viral cytokine, cmvIL-10, on exosome production by highly metastatic breast cancer cells.

MDA-MB-231 cells were cultured in vitro, …

Structural And Functional Interactions Between Bro1 Domain Of Human Alix Protein And Nucleocapsid Packaging Rna Complex From Hiv, Scott Gross

Graduate School of Biomedical Sciences Theses and Dissertations

A virus is only as powerful as its ability to spread. Enveloped retroviruses, namely HIV-1, use exocytosis pathways that normal host cells use to release particles from the plasma membrane. The main pathways of interest in this study are the Endosomal Sorting Complex Required for Transport (ESCRT) and adjacent ALIX pathways. The ESCRT pathway is especially important for degradation of receptor/cargo complexes that form Multi-Vesicular Bodies (MVBs). Currently, there is no known therapy that targets this endosomal pathway, which would prevent the spread of the virus to other cells. The virus has adapted to jump from pathway to pathway when …

Adapting The Standard Sir Disease Model In Order To Track And Predict The Spreading Of The Ebola Virus Using Twitter Data, Armin Smailhodzic

Masters Theses & Specialist Projects

A method has been developed to track infectious diseases by using data mining of active Twitter accounts and its efficacy was demonstrated during the West African Ebola outbreak of 2014. Using a meme based n-gram semantic usage model to search the Twitter database for indications of illness, flight and death from the spread of Ebola in Africa, principally from Guinea, Sierra Leone and Liberia. Memes of interest relate disease to location and severity and are coupled to the density of Tweets and re-Tweets. The meme spreads through the community of social users in a fashion similar to nonlinear wave propagation- …

Sexual Relationships Outside Primary Partnerships And Abstinence Are Associated With Lower Adherence And Adherence Gaps: Data From The Partners Prep Ancillary Adherence Study, Alexander Kintu, Susan E. Hankinson, Raji Balasubramanian, Karen Ertel, Elioda Tumwesigye, David Bangsberg, Jessica E. Haberer

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objective—To assess the role of sexual relationships on levels and patterns of adherence to medication for pre-exposure prophylaxis (PrEP) against HIV.

Methods—We enrolled 1,147 HIV-negative individuals in long-term serodiscordant relationships at three sites in Uganda from the Partners PrEP Study- a randomized placebo-controlled trial of daily oral tenofovir and emtricitabine/tenofovir. We used generalized estimation equations to assess the effects of sexual relationships on low adherence (

Results—Fifty-three percent were male, 51% were 18-34 years and 24% were polygamous. Participants who reported sex in the past month with someone other than their primary partner and with

Conclusions—Risk of low overall adherence …

Super Learner Analysis Of Electronic Adherence Data Improves Viral Prediction And May Provide Strategies For Selective Hiv Rna Monitoring, Maya L. Petersen, Erin Ledell, Joshua Schwab, Varada Sarovar, Robert Gross, Nancy Reynolds, Jessica E. Haberer, Kathy Goggin, Carol E. Golin, Julia Arnsten, Marc Rosen, Robert H. Remien, David Etoori, Ira B. Wilson, Jane M. Simoni, Judith A. Erlen, Mark J. Van Der Laan, Honghu Liu, David Bangsberg

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objective—Regular HIV RNA testing for all HIV positive patients on antiretroviral therapy (ART) is expensive and has low yield since most tests are undetectable. Selective testing of those at higher risk of failure may improve efficiency. We investigated whether a novel analysis of adherence data could correctly classify virological failure and potentially inform a selective testing strategy.

Design—Multisite prospective cohort consortium.

Methods—We evaluated longitudinal data on 1478 adult patients treated with ART and monitored using the Medication Event Monitoring System (MEMS) in 16 United States cohorts contributing to the MACH14 consortium. Since the relationship between adherence and virological failure is …

Anal Cancer Risk Factor Management Practices And The Barriers And Facilitators Of Addressing Anal Health In The Hiv Primary Care Setting, Crystal Martin Walker

Theses and Dissertations (ETD)

Background: The incidence of anal cancer is only 1-2 per 100,000 people in the general population, but in people living with HIV and AIDS (PLWHA), the incidence is far greater by about 80 times. This is a striking disproportion, and it is vital for the healthcare provider and healthcare system to become more attentive to the risk of anal cancer in high-risk populations such as PLWHA. There are a number of modifiable risk factors for anal cancer in PLWHA such as smoking, non-adherence to antiretroviral therapy (ART), and risky sexual behaviors. The HIV primary care provider (HIV PCP) plays a …

Use Of N-Acetylcysteine In Children With Fulminant Hepatic Failure Caused By Acute Viral Hepatitis, Ali Faisal Saleem, Qalab Abbas, Anwarul Haque

Department of Paediatrics and Child Health

Objective: To determine the efficacy of N-acetylcysteine (NAC) in children aged > 1 month to 16 years admitted with Fulminant Hepatic Failure (FHF) secondary to Acute Viral Hepatitis (AVH) in a tertiary care center of a developing country.

Study Design: Analytical study.

Place and Duration of Study: Department of Paediatrics, The Aga Khan University Hospital, Karachi, Pakistan, from January 2007 to December 2011.

Methodology: Medical records of children (> 1 month - 16 years) with FHF admitted with AVH of known etiology who received NAC were reviewed retrospectively. Liver function tests (mean ± SD) at baseline, 24 hours after NAC and …

Impact Of Social And Cultural Factors On Teenage Pregnancy, Devi Akella, Melissa Jordan

Journal of Health Disparities Research and Practice

United States has the highest level of teenage pregnancy amongst the industrialized nations. Further, the level of teenage pregnancy is highest amongst the minority population. This research study examines the reasons behind high rates of early childbirth amongst African American teenagers. This study uses Bandura’s (1977) Social Learning Theory to deconstruct the factors, which influence and manipulate the overall behavior of the teenagers and initiates them to choose early motherhood over education and career. To ensure better quality of empirical data, the authors collaborated with the pregnant teenagers and a local non-profit community agency using a phenomenological analysis.

True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring, Debra A. Benator, Angelo Elmi, Manuel D. Rodriguez, Howard B. Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires

Medicine Faculty Publications

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 …

True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring., Debra A Benator, Angelo Elmi, Manuel D Rodriguez, Howard B Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires

Medicine Faculty Publications

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 …

Multicountry Prospective Clinical Evaluation Of Two Enzyme-Linked Immunosorbent Assays And Two Rapid Diagnostic Tests For Diagnosing Dengue Fever, Subhamoy Pal, Allison Dauner, Andrea Valks, Brett M. Forshey, Kanya C. Long, Butsaya Thaisomboonsuk, Gloria Sierra, Victor Picos, Sara Talmage, Amy C. Morrison, Eric S. Halsey, Guillermo Comach, Chadwick Yasuda, Michael Loeffelholz, Richard G. Jarman, Stefan Fernandez, Ung Sam An, Tadeusz J. Kochel, Louis E. Jasper, Shuenn-Jue L. Wu

Faculty Publications

We evaluated four dengue diagnostic devices from Alere, including the SD Bioline Dengue Duo (nonstructural [NS] 1 Ag and IgG/IgM), the Panbio Dengue Duo Cassette (IgM/IgG) rapid diagnostic tests (RDTs), and the Panbio dengue IgM and IgG capture enzyme-linked immunosorbent assays (ELISAs) in a prospective, controlled, multicenter study in Peru, Venezuela, Cambodia, and the United States, using samples from 1,021 febrile individuals. Archived, well-characterized samples from an additional 135 febrile individuals from Thailand were also used. Reference testing was performed on all samples using an algorithm involving virus isolation, in-house IgM and IgG capture ELISAs, and plaque reduction neutralization tests …

Strengthening The Detection Of And Early Response To Public Health Emergencies: Lessons From The West African Ebola Epidemic, Mark J. Siedner, Lawrence O. Gostin, Hilarie H. Cranmer, John D. Kraemer

Georgetown Law Faculty Publications and Other Works

Background

In the year since the World Health Organization (WHO) notified of an Ebola outbreak in West Africa, more than 24,000 cases have been reported and over 10,000 individuals have died. Moreover, countless non-Ebola deaths have occurred as a result of health system closings and an international aid effort in the $USD billions has been invested in control efforts. While the international response to the West African Ebola virus disease epidemic eventually exemplified the great potential of the global public health community, the protracted early response also revealed critical gaps, which likely resulted in exacerbation of the epidemic. It is …

P-23 Variations In Microbiota Of Culex (Melanoconion) Ocossa And Culex (Culex) Declaratoracross Periurban And Rural Environments, M. Nelson Starkey

Honors Scholars & Undergraduate Research Poster Symposium Programs

Mosquitoes serve as the primary mode of transmission for many tropical infections such as Venezuelan equine encephalitis virus, dengue virus, and malaria. Therefore, mosquitoes are an important area of study for disease control. This study examined the differences in gut microbiota of Culex melanoconion species across two different habitats: periurban and rural. Mosquitoes were collected from locations around Iquitos, Peru and their gut bacterial DNA was extracted and analyzed. Based on previous studies it is believed that the bacterial flora will differ among mosquitoes reared in different locations.

Know Your Audience: Predictors Of Success For A Patient-Centered Texting App To Augment Linkage To Hiv Care In Rural Uganda, Mark J. Siedner, Data Santorino, Jessica E. Haberer, David Bangsberg

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background: Despite investments in infrastructure and evidence for high acceptability, few mHealth interventions have been implemented in sub-Saharan Africa.

Objective: We sought to (1) identify predictors of uptake of an mHealth application for a low-literacy population of people living with HIV (PLWH) in rural Uganda and (2) evaluate the efficacy of various short message service (SMS) text message formats to optimize the balance between confidentiality and accessibility.

Methods: The trial evaluated the efficacy of a SMS text messaging app to notify PLWH of their laboratory results and request return to care for those with abnormal test results. Participants with a …

Assessing Usual Care In Clinical Trials, Judith A. Erlen, Lisa K. Tamres, Nancy Reynolds, Carol E. Golin, Marc I. Rosen, Robert H. Remien, Julie W. Banderas, Neil Schneiderman, Glenn Wagner, David Bangsberg, Honghu Liu

OHSU-PSU School of Public Health Faculty Publications and Presentations

Researchers designing clinical trials often specify usual care received by participants as the control condition expecting that all participants receive usual care regardless of group assignment. The assumption is that the groups in the study are affected similarly. We describe the assessment of usual care within the 16 studies in MACH 14, a multi-site collaboration on adherence to antiretroviral therapy. Only five of the studies in MACH 14 assessed usual care. Assessment protocols varied as did the timing and frequency of assessments. All usual care assessments addressed patient education focused on HIV, HIV medications, and medication adherence. Our findings support …

Lessons Learned: Exploratory Study Of A Hiv/Aids Prevention Intervention For African American Women Who Have Experienced Intimate Partner Violence, Michele A. Rountree

Journal of Health Disparities Research and Practice

Given the prevalence and co-occurring nature of HIV and intimate partner violence among African American women there is a need for a risk reduction intervention. This study explored the results from an exploratory study of an HIV/AIDS prevention intervention for African-American women who have experienced intimate partner violence. The emphasis of this study is to identify lessons learned to guide future research.

Recruitment for the feasibility study was done in two waves over a period of three months. During the first wave, 22 participants were recruited for the intervention group, and in the second wave, 25 participants were in the …

Editors' Notes-Women Of Color Sexual Health Across The Lifespan, Marya Shegog, Melva Thompson-Robinson

Journal of Health Disparities Research and Practice

No abstract provided.

Editors' Notes: Men Of Color Sexual Health Across The Lifespan, Marya Shegog, Melva Thompson-Robinson

Journal of Health Disparities Research and Practice

No abstract provided.

Book Review: Stigma, Discrimination, And Living With Hiv/Aids: A Cross-Cultural Perspective, Joyce Addo-Atuah, William Lundmark

Touro University Libraries Publications and Research

The authors present a review of the book Stigma, Discrimination, and Living with HIV/AIDS: A Cross-Cultural Perspective.

Ebola Scare And Measles Resurgence: Mandatory Isolation/Quarantine And Vaccination, Mark C. Aita Md, Takeem T. Ragland Ma

Journal of Health Ethics

Public outcry for radical isolation and quarantine policies followed the first Ebola diagnosis in the United States when Eric Duncan, upon his return home Oct 2014 from West Africa, then in the midst of a catastrophic Ebola epidemic, tested positive for Ebola. Likewise, the Dec 2014 Disneyland measles outbreak unleashed an angry backlash against parents who refused to have their children vaccinated; and there was public momentum to repeal all legal exemptions to mandatory vaccination of school children. This paper presents an ethical and legal analysis to adjudicate the issue which is at stake in both controversies; namely the inherent …

Polio Eradication And Health Systems In Karachi: Vaccine Refusals In Context, Svea Closser, Rashid Jooma, Emma Varley, Naina Qayyum, Sonia Rodrigues, Akasha Sarwar, Patricia Omidian

Section of Neurosurgery

Community and health worker engagement will be key to polio eradication in Karachi, Pakistan. In this study, the authors conducted participant observation, interviews, and a document review in SITE Town, Karachi, an area that in recent years has harbored poliovirus. SITE’s diverse population includes large numbers of internally displaced persons who are disproportionately affected by polio and are more likely than other populations to refuse the polio vaccine. Vaccine acceptance and worker motivation in SITE Town were shaped by the discrepancy in funding and attention for polio eradication campaigns as compared with routine services. Parental vaccine refusals stemmed from a …

Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Kaposi sarcoma (KS) herpesvirus (KSHV) infection of endothelial cells (EC) is associated with strong induction of heme oxygenase-1 (HO-1), a stress-inducible host gene that encodes the rate-limiting enzyme responsible for heme catabolism. KS is an angioproliferative tumor characterized by the proliferation of KSHV-infected spindle cells, and HO-1 is highly expressed in such cells. HO-1 converts the pro-oxidant, proinflammatory heme molecule into metabolites with antioxidant, antiinflammatory, and proliferative activities. Previously published work has shown that KSHV-infected EC in vitro proliferate in response to free heme in a HO-1-dependent manner, thus implicating virus-enhanced HO-1 activity in KS tumorigenesis. The present study investigated …

Incomplete Adherence Among Treatment-Experienced Adults On Antiretroviral Therapy In Tanzania, Uganda And Zambia, Julie A. Denison, Olivier Koole, Sharon Tsui, Joris Menten, Kwasi Torpey, Eric Van Praag, Ya Diul Mukadi, Robert Colebunders, Andrew F. Auld, Simon G. Agolory, Jonathan Kaplan, Modest Mulenga, Gideon Kwesigabo, Fred Wabwire-Mangen, David Bangsberg

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objectives—To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa.

Design—A cross-sectional study.

Methods—Systematically selected ART clients (≥18 years; on ART ≥6 months) attending 18 facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index ≥48 consecutive hours of missed ART), healthcare provider estimates and the pharmacy medication possession ratio (MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association …

A Retrospective And Prospective Analysis Of The West African Ebola Virus Disease Epidemic: Robust National Health Systems At The Foundation And An Empowered Who At The Apex, Lawrence O. Gostin, Eric A. Friedman

Georgetown Law Faculty Publications and Other Works

The West African Ebola epidemic is a pivotal moment for the global health system. Just as the depth of the crisis ultimately spurred an unprecedented response, the failures of leadership demand innovative reforms. This analysis offers a template for these reforms, responding to the profound harms posed by fragile national health systems, delays in the international response, deficient resource mobilization, ill-defined responsibilities, and insufficient coordination. The scope of the reforms must address the failures evident in the Ebola response, as well as entrenched weaknesses that enabled the epidemic to reach its heights, transforming the existing inchoate, organically developed global health …