Medicine and Health Sciences Commons^™

The Pseudomonas Aeruginosa Magnesium Transporter Mgte Inhibits Transcription Of The Type Iii Secretion System, Gregory G. Anderson, Timothy L. Yahr, Rustin R. Lovewell, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (CF). These long-term infections are maintained by bacterial biofilm formation in the CF lung. We have recently developed a model of P. aeruginosa biofilm formation on cultured CF airway epithelial cells. Using this model, we discovered that mutation of a putative magnesium transporter gene, called mgtE, led to increased cytotoxicity of P. aeruginosa toward epithelial cells. This altered toxicity appeared to be dependent upon expression of the type III secretion system (T3SS). In this study, we found that mutation of mgtE results in increased T3SS …

The Face Of Felt Stigma: Experiences Of Puerto Ricans Living With Hiv In Allentown, Pa, M Reyes Ba, Julio Jiménez Md, Joseph L. Yozviak Do, Facp, Timothy J. Friel Md, D Adams Psyd, Cynthia Beitler, Eric J. Gertner Md, Mph, E Rivera Ba, L Santiago Phd

Department of Medicine

No abstract provided.

Interferon Regulatory Factor 3-Dependent Pathways Are Critical For Control Of Herpes Simplex Virus Type 1 Central Nervous System Infection, Vineet D. Menachery, Tracy J. Pasieka, David A. Leib

Dartmouth Scholarship

The initiation of the immune response at the cellular level relies on specific recognition molecules to rapidly signal viral infection via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways. The absence of IRF-3 would be expected to render such pathways inoperative and thereby significantly affect viral infection. Unexpectedly, a previous study found no significant change in herpes simplex virus (HSV) pathogenesis in IRF-3^−/− mice following intravenous HSV type 1 (HSV-1) challenge (K. Honda, H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi, Nature 434:772-777, 2005). In contrast, the …

Concurrent Sexual Partnerships Do Not Explain The Hiv Epidemics In Africa: A Systematic Review Of The Evidence, Larry Sawers, Eileen Stillwaggon

Economics Faculty Publications

The notion that concurrent sexual partnerships are especially common in sub-Saharan Africa and explain the region’s high HIV prevalence is accepted by many as conventional wisdom. In this paper, we evaluate the quantitative and qualitative evidence offered by the principal proponents of the concurrency hypothesis and analyze the mathematical model they use to establish the plausibility of the hypothesis.

We find that research seeking to establish a statistical correlation between concurrency and HIV prevalence either finds no correlation or has important limitations. Furthermore, in order to simulate rapid spread of HIV, mathematical models require unrealistic assumptions about frequency of sexual …

Primary Human Mammary Epithelial Cells Endocytose Hiv-1 And Facilitate Viral Infection Of Cd4+ T Lymphocytes, Stephanie M. Dorosko, Ruth I. Connor

Dartmouth Scholarship

The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4(+) cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4(+) cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4(+) target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription …

The Staphylococcus-Specific Gene Rsr Represses Agr And Virulence In Staphylococcus Aureus, Sandeep Tamber, Dindo Reyes, Niles P. Donegan, Joseph D. Schwartzman, Ambrose L. Cheung, Guido Memmi

Dartmouth Scholarship

The expression of virulence factors in Staphylococcus aureus is tightly coordinated by a vast network of regulatory molecules. In this report, we characterize a genetic locus unique to staphylococci called rsr that has a role in repressing two key virulence regulators, sarR and agr. Using strain SH1000, we showed that the transcription of virulence effectors, such as hla, sspA, and spa, is altered in an rsr mutant in a way consistent with agr upregulation. Analysis of RNAIII expression of the agr locus in rsr and rsr-sarR mutants indicated that rsr likely contributes to agr expression independently …

Mononucleosis And Antigen-Driven T Cell Responses Have Different Requirements For Interleukin-2 Signaling In Murine Gammaherpesvirus Infection, Michael Molloy, Weijun Zhang, Edward Usherwood

Dartmouth Scholarship

Interleukin-2 (IL-2) has been implicated as being necessary for the optimal formation of primary CD8⁺ T cell responses against various pathogens. Here we have examined the role that IL-2 signaling plays in several aspects of a CD8⁺ T cell response against murine gammaherpesvirus 68 (MHV-68). Exposure to MHV-68 causes a persistent infection, along with infectious mononucleosis, providing a model for studying these processes in mice. Our study indicates that CD25 is necessary for optimal expansion of the antigen-specific CD8⁺ T cell response but not for the long-term memory response. Contrastingly, IL-2 signaling through CD25 is absolutely required …

The Role Of Unrealistic Optimism In Explaining Preventive Behaviors In High Versus Low Endemic Malaria Settings In Belize, Daniel G. Handysides

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Of all the diseases an individual can encounter in the world, malaria is one of the most destructive. Simple measures like sleeping under a bednet would greatly reduce the burden (Abeku, 2007). When people estimate their risk relative to others, they are most often unrealistically optimistic, which may explain why those at risk often fail to perform behaviors, such as using a bednet that will reduce their risk. However, one study showed that people at high risk for malaria held pessimistic perceptions of their risk for the disease, but the reasons for this finding are unclear (Morrison, Ager, & …

Controle De Infecção Em Clínicas De Cirurgia Plástica / Infection's Control In Plastic Surgery Clinics, Everton Fernando Alves

Everton Fernando Alves

A infecção é a mais frequente e grave complicação que acomete pacientes que procuram serviços estéticos e/ou funcionais em clínicas de cirurgia plástica. Uma infecção hospitalar eleva os custos do processo, tanto para o paciente quanto para a empresa. Diante disso, torna-se importante a instalação de uma comissão de controle de infecção hospitalar, tendo como responsável um enfermeiro. A importância deste profissional se dá por meio da organização da Central de Material Estarilizado (CME), bem como do estabelecimento de outras medidas efetivas para a prevenção e controle de infecções nas clínicas apresentadas ao longo desse artigo.

Human Papillomavirus And Survival Of Patients With Oropharyngeal Cancer., K Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I Rosenthal, Phuc Felix Nguyen-Tân, William H Westra, Christine H Chung, Richard C Jordan, Charles Lu, Harold Kim, Rita S. Axelrod, Md, C Craig Silverman, Kevin P Redmond, Maura L Gillison

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.

METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive …

Anti-Hiv Activity In Cervical-Vaginal Secretions From Hiv-Positive And -Negative Women Correlate With Innate Antimicrobial Levels And Igg Antibodies, Mimi Ghosh, John V. Fahey, Zheng Shen, Timothy Lahey, Susan Cu-Uvin, Zhijin Wu, Kenneth Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Dartmouth Scholarship

Background: We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(2) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (2) women inhibit HIV infection.

Methodology/Principal Findings: CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(2) women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti- HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and …

The Efficacy And Safety Of Insulin-Sensitizing Drugs In Hiv-Associated Lipodystrophy Syndrome: A Meta-Analysis Of Randomized Trials, Siddharth H. Sheth, Robin J. Larson

Dartmouth Scholarship

HIV-associated lipodystrophy syndrome (HALS) is characterized by insulin resistance, abnormal lipid metabolism and redistribution of body fat. To date, there has been no quantitative summary of the effects of insulin sensitizing-agents for the treatment of this challenging problem. We searched MEDLINE, the Cochrane Library, clinical trial registries, conference proceedings and references for randomized trials evaluating rosiglitazone, pioglitazone or metformin in patients with evidence of HALS (last update December 2009). Two reviewers independently abstracted data and assessed quality using a standard form. We contacted authors for missing data and calculated weighted mean differences (WMD) and 95% confidence intervals (CI) for each …

Role Of Pknb Kinase In Antibiotic Resistance And Virulence In Community-Acquired Methicillin-Resistant Staphylococcus Aureus Strain Usa300, S. Tamber, J. Schwartzman, A. L. Cheung

Dartmouth Scholarship

The regulation of cellular processes by eukaryote-like serine/threonine kinases is widespread in bacteria. In the last 2 years, several studies have examined the role of serine/threonine kinases in Staphylococcus aureus on cell wall metabolism, autolysis, and virulence, mostly in S. aureus laboratory isolates in the 8325-4 lineage. In this study, we showed that the pknB gene (also called stk1) of methicillin-resistant S. aureus (MRSA) strain COL and the community-acquired MRSA (CA-MRSA) strain USA300 is involved in cell wall metabolism, with the pknB mutant exhibiting enhanced sensitivity to β-lactam antibiotics but not to other classes of antibiotics, including aminoglycosides, ciprofloxacin, …

Pseudomonas Aeruginosa Evasion Of Phagocytosis Is Mediated By Loss Of Swimming Motility And Is Independent Of Flagellum Expression, Eyal Amiel, Rustin R. Lovewell, George A. O'Toole, Deborah A. Hogan, Brent Berwin

Dartmouth Scholarship

Pseudomonas aeruginosa is a pathogenic Gram-negative bacterium that causes severe opportunistic infections in immunocompromised individuals; in particular, severity of infection with P. aeruginosa positively correlates with poor prognosis in cystic fibrosis (CF) patients. Establishment of chronic infection by this pathogen is associated with downregulation of flagellar expression and of other genes that regulate P. aeruginosa motility. The current paradigm is that loss of flagellar expression enables immune evasion by the bacteria due to loss of engagement by phagocytic receptors that recognize flagellar components and loss of immune activation through flagellin-mediated Toll-like receptor (TLR) signaling. In this work, we employ bacterial …

Improving Sexual Health, P.U.L.S.E., And E.R.O.S. At California Polytechnic State University, San Luis Obispo, Megan (Meg) Rust

Psychology and Child Development

This project is designed to update and refine EROS educators’ knowledge of sexual health and to gain insight into Cal Poly students’ general knowledge of sexual health. Educators are given extensive training during the entire quarter before they begin their positions, but information is constantly changing. This project intends to initiate up to date informational tools that can be revised as new psychological or medical discoveries are made in the realm of sexuality and sexual health.

Crimean-Congo Hemorrhagic Fever In A Dengue-Endemic Region: Lessons For The Future., Farheen Ali, Taimur Saleem, Umair Khalid, Syed Faisal Mahmood, Bushra Jamil

Department of Medicine

Crimean-Congo hemorrhagic fever and dengue hemorrhagic fever are endemic in Pakistan. However, the overlap of geographic distribution and early clinical features between the two conditions make a reliable diagnosis difficult in the initial stage of illness. A 16-year-old boy presented with a history of hematemesis and high-grade fever. A preliminary diagnosis of dengue hemorrhagic fever was made and supportive treatment was instituted; however, the patient continued to deteriorate clinically. Dengue IgM antibody testing was negative on the third day of admission. Qualitative polymerase chain reaction test for Crimean-Congo hemorrhagic fever viral RNA was sent but the patient expired shortly after …

Paracoccidiomycosis And Hiv/Aids: A Common Problem In An Uncommon Location, Astrid Radermacher Do, Joseph L. Yozviak Do, Facp, Marcelo Gareca Md

Department of Medicine

No abstract provided.

Structure Of Vibrio Cholerae Toxt Reveals A Mechanism For Fatty Acid Regulation Of Virulence Genes, Michael J. Lowden, Karen Skorupski, Maria Pellegrini, Michael G. Chiorazzo, Ronald K. Taylor, F. Jon Kull

Dartmouth Scholarship

Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 A resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding that …

Ct And Mri Features Following Uterine Fibroid Embolization, Sachit Verma Md, Carin F. Gonsalves Md, Oksana H. Baltarowich Md, Donald G. Mitchell Md, Anna Lev-Toaff Md, Diane Bergin Md

Department of Radiology Faculty Papers

Uterine artery embolization (UAE) is an effective treatment for symptomaticuterine fibroids. Magnetic resonance (MR) imaging is typically employed to evaluate the uterus following UAE for fibroid infarction, size, location change, persistent enhancement, changes in adenomyosis and uterine necrosis. Variable pattern of calcification on computed tomography (CT) can differentiate embolic particles and fibroid involution. CT following UAE may be requested because of acute pelvic pain or chest discomfort or pyrexia and/or for complications that may require treatment in acute phase. Visualization of gas in uterus and uterine vessels following UAE is an expected finding that should not be misinterpreted as a …

Crystal Structure Of The Cystic Fibrosis Transmembrane Conductance Regulator Inhibitory Factor Cif Reveals Novel Active-Site Features Of An Epoxide Hydrolase Virulence Factor, Christopher D. Bahl, Christophe Morisseau, Jennifer M. Bomberger, Bruce A. Stanton, Bruce D. Hammock, George A. O'Toole, Dean R. Madden

Dartmouth Scholarship

Cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) is a virulence factor secreted by Pseudomonas aeruginosa that reduces the quantity of CFTR in the apical membrane of human airway epithelial cells. Initial sequence analysis suggested that Cif is an epoxide hydrolase (EH), but its sequence violates two strictly conserved EH motifs and also is compatible with other alpha/beta hydrolase family members with diverse substrate specificities. To investigate the mechanistic basis of Cif activity, we have determined its structure at 1.8-A resolution by X-ray crystallography. The catalytic triad consists of residues Asp129, His297, and Glu153, which are conserved across the …

Optimal Dynamic Policies For Influenza Management, Michael Ludkovski, Jarad Niemi

Jarad Niemi

Management policies for influenza outbreaks balance the expected morbidity and mortality costs versus the cost of intervention policies. We present a methodology for dynamic determination of optimal policies in a completely observed stochastic compartmental model with parameter uncertainty. Our approach is simulation-based and searches the full set of sequential control strategies. For each time point, it generates a policy map describing the optimal intervention to implement as a function of outbreak state and Bayesian parameter posteriors. As a running example, we study a stochastic SIR model with isolation and vaccination as two possible interventions. Numerical simulations based on a classic …

Prevalence Of Hepatitis B And C Viral Infections In Pakistan: Findings Of A National Survey Appealing For Effective Prevention And Control Measures, H Qureshi, K M. Bile, Rashid Jooma, S E. Alam, H U R. Afridi

Section of Neurosurgery

A prevalence survey on hepatitis B and C infections was carried out to obtain national estimates and assess epidemiological dynamics and underlying risk factors. Overall prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) of 2.5% and 4.8%, respectively, reflected a combined infection rate of 7.6% in the general population, consistent with an ongoing high burden of chronic liver disease (CLD). There was significant association of these viral infections with a range of risk factors led by reuse of syringes. These findings validate currently implemented strategies by the national programme for the control of hepatitis viral infections, …

Neuroaids In Africa, Kevin Robertson, Jeff Liner, James Hakim, Jean-Louis Sankalé, Igor Grant, Scott Letendre, David Clifford, Amadou Gallo Diop, Assan Jaye, Georgette Kanmogne, Alfred Njamnshi, T. Dianne Langford, Tufa Gemechu Weyessa, Charles Wood, Mwanza Banda, Mina Hosseinipour, Ned Sacktor, Noeline Nakasuja, Paul Bangirana, Robert Paul, John Joska, Joseph Wong, Michael Boivin, Penny Holding, Betsy Kammerer, Annelies Van Rie, Prudence Ive, Avindra Nath, Kathy Lawler, Clement Adebamowo, Walter Royal Iii, Jeymohan Joseph

Nebraska Center for Virology: Faculty Publications

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting “NeuroAIDS in Africa.” This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, …

Functional Properties Of The Hiv-1 Subtype C Envelope Glycoprotein Associated With Mother-To-Child Transmission, Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the …

Chronology And Evolution Of The Hiv-1 Subtype C Epidemic In Ethiopia, Damien C. Tully, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To reconstruct the onset date and evolutionary history of the HIV-1 subtype C epidemic in Ethiopia - one of the earliest recorded subtype C epidemics in the world.

Design—HIV-1 C env sequences with a known sampling year isolated from HIV-1 positive patients from Ethiopia between 1984 and 2003.

Methods—Evolutionary parameters including origin and demographic growth patterns were estimated using a Bayesian coalescent-based approach under either strict or relaxed molecular clock models.

Results—Bayesian evolutionary analysis indicated a most recent common ancestor date of 1965 with three distinct epidemic growth phases. Regression analysis of root-to-tip distances revealed a highly similar estimate for …

Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood

Nebraska Center for Virology: Faculty Publications

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi’s sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, …

Chlorella Viruses Encode Most, If Not All, Of The Machinery To Glycosylate Their Glycoproteins Independent Of The Endoplasmic Reticulum And Golgi, James L. Van Etten, James Gurnon, Giane M. Yanai-Balser, David Dunigan, Michael V. Graves

Nebraska Center for Virology: Faculty Publications

In contrast to all other viruses that use the host machinery located in the endoplasmic reticulum and Golgi to glycosylate their glycoproteins, the large dsDNA-containing chlorella viruses encode most, if not all, of the components to glycosylate their major capsid proteins. Furthermore, all experimental results indicate that glycosylation occurs independent of the endoplasmic reticulum and Golgi. (Review article)

Referral Mechanism Improves Uptake Of Art Services For Hiv+ Fp Clients, Population Council

Reproductive Health

An operations research intervention by the Population Council in Kenya aimed to design a referral framework for linking HIV‐positive family planning (FP) clients to treatment and care in selected health facilities. The project also assessed the acceptability and effectiveness in increasing the number of eligible HIV‐positive FP clients receiving HIV care and treatment services. This summary details the effort to improve the linkage between FP services and comprehensive care centers that led to a dramatic increase in the proportions of HIV-positive clients in FP clinics who go on to receive HIV/AIDS treatment and care services at the same facility. Recommendations …

Introducing A Multi-Site Program For Early Diagnosis Of Hiv Infection Among Hiv-Exposed Infants In Tanzania, Harriet Nuwagaba-Biribonwoha, Bazghina Werq-Semo, Aziz Abdallah, Amy Cunningham, John G. Gamaliel, Sevestine Mtunga, Victoria Nankabirwa, Isaya Malisa, Luis F. Gonzalez, Charles Massambu, Denis Nash, Jessica Justman, Elaine J. Abrams

Publications and Research

Background: In Tanzania, less than a third of HIV infected children estimated to be in need of antiretroviral therapy (ART) are receiving it. In this setting where other infections and malnutrition mimic signs and symptoms of AIDS, early diagnosis of HIV among HIV-exposed infants without specialized virologic testing can be a complex process. We aimed to introduce an Early Infant Diagnosis (EID) pilot program using HIV DNA Polymerase Chain Reaction (PCR) testing with the intent of making EID nationally available based on lessons learned in the first 6 months of implementation.

Methods: In September 2006, a molecular biology laboratory at …

Training Service Providers Increases Tb Screening In Postnatal Care, Population Council

Reproductive Health

This document summarizes a Population Council operations research project undertaken in collaboration with the Kenya Ministry of Health to develop and pilot-test an intervention to improve TB screening, case detection, treatment, and care among postnatal clients. The intervention demonstrated that it is feasible to use postnatal care services as a platform to increase TB screening and case detection. Training providers, giving them job-aids, and strengthening client flow within the facility also improved the overall quality of care that the clients received. The actual number of cases of TB detected was extremely low, however; thus the report recommends that the Ministry …