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A Highly Stable Prefusion Rsv F Vaccine Derived From Structural Analysis Of The Fusion Mechanism, Anders Krarup, Daphné Truan, Polina Furmanova-Hollenstein, Lies Bogaert, Pascale Bouchier, Ilona Bisschop, Myra Widjojoatmodjo, Roland Zahn, Hanneke Schuitemaker, Jason Mclellan, Johannes Langedijk

Dartmouth Scholarship

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. Recently, a promising vaccine antigen based on the RSV fusion protein (RSV F) stabilized in the native prefusion conformation has been described. Here we report alternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion peptide. A limited number of unique mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increase expression levels. This highly stable prefusion …

A Unique Biofilm In Human Deep Mycoses: Fungal Amyloid Is Bound By Host Serum Amyloid P Component, Melissa C. Garcia-Sherman, Tracy Lundberg, Richard E. Sobonya, Peter N. Lipke, Stephen A. Klotz

Publications and Research

Background/Objectives We have demonstrated the presence of Candida cell surface amyloids that are important in aggregation of fungi and adherence to tissue. Fungal amyloid was present in invasive human candidal infections and host serum amyloid P component (SAP) bound to the fungal amyloid. SAP is a protease-resistant glycoprotein that binds avidly to amyloid and interferes with host defence, especially against bacterial pathogens for which neutrophils are important. In this study, we investigated whether biofilm of fungal amyloid and SAP was a feature of other disseminated fungal infections. Methods Tissue specimens from 15 autopsies were systematically evaluated with multiple histochemical stains …

Metalloregulation Of Helicobacter Pylori Physiology And Pathogenesis, Kathryn P. Haley, Jennifer A. Gaddy

Peer Reviewed Articles

Helicobacter pylori is a Gram-negative spiral-shaped bacterium that colonizes over half of the world's population. Chronic H. pylori infection is associated with increased risk for numerous disease outcomes including gastritis, dysplasia, neoplasia, B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma), and invasive adenocarcinoma. The complex interactions that occur between pathogen and host are dynamic and exquisitely regulated, and the relationship between H. pylori and its human host are no exception. To successfully colonize, and subsequently persist, within the human stomach H. pylori must temporally regulate numerous genes to ensure localization to the gastric lumen and coordinated expression of virulence factors …

Assessment Of Nutritional Status In Pregnant Women On Opioid Maintenance Therapy, Shikhar Shrestha

Pharmaceutical Sciences ETDs

Objectives: Patients who use substances or those who are on opioid maintenance therapy could be at risk of inadequate nutrition. These inadequacies could translate to adverse outcomes during pregnancy. The objective of this study was to determine differences in dietary macro and micronutrient intake in pregnant women on OMT compared to healthy controls. Methods: Participants from a parent prospective cohort study ENRICH' were classified into two groups: OMT users and healthy controls. Inclusion into the nutritional analysis was based on eligibility criteria of completion of food frequency questionnaire administered during hospital stay after delivery, absence of heavy drinking and adequate …

Healthy You, Lehigh Valley Health Network

Healthy You

No abstract provided.

Progress Notes, Lehigh Valley Health Network

Progress Notes

No abstract provided.

Combating Racial Health Disparities Through Medical Education: The Need For Anthropological And Genetic Perspectives In Medical Training, Deborah A. Bolnick

Human Biology Open Access Pre-Prints

Despite major public health initiatives, significant disparities persist among racially and ethnically defined groups in the prevalence of disease, access to medical care, quality of medical care, and health outcomes for common causes of morbidity and mortality in the United States. It is critical that we develop new and creative strategies to address such inequities; mitigate the social, environmental, institutional, and genetic determinants of poor health; and combat the persistence of racial profiling in clinical contexts that further exacerbates racial/ethnic health disparities. This article argues that medical education is a prime target for intervention and that anthropologists and human population …

Research News Newsletter, Fall 2015, Research News Newsletter, Stony Brook University.

Research News

Quarterly newsletter from the Office of the Vice President for Research

Clostridium Difficile Infections Before And During Use Of Ultraviolet Disinfection, Aarathi Nagaraja, Paul Visintainer, Janet P. Haas, Jonathan Menz, Gary P. Wormser, Marisa A. Montecalvo

NYMC Faculty Publications

BACKGROUND: We previously reported a significant decrease in hospital-acquired (HA) Clostridium difficile infection (CDI) coincident with the introduction of pulsed xenon ultraviolet light for room disinfection (UVD). The purpose of this study was to evaluate CDI cases in greater detail to understand the effect of UVD. METHODS: CDI rates (HA and community acquired [CA]), CDI patient length of stay, room occupancy, and number of days between a CDI case in a room and an HA CDI case in the same room were studied for the first year of UVD compared with the 1-year period pre-UVD. RESULTS: Compared with pre-UVD, during …

Meningeal Infiltration Of The Spinal Cord By Non-Classically Activated B Cells Is Associated With Chronic Disease Course In A Spontaneous B Cell-Dependent Model Of Cns Autoimmune Disease, Amy K. Dang, Yodit Tesfagiorgis, Rajiv W. Jain, Heather C. Craig, Steven M. Kerfoot

Microbiology & Immunology Publications

We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4⁺ T cell infiltration was pervasive throughout the white and in some cases gray matter. B cells were almost exclusively restricted to …

Local Bacteria Affect The Efficacy Of Chemotherapeutic Drugs, Panos Lehouritis, Joanne Cummins, Michael Stanton, Carola T Murphy, Florence O Mccarthy, Gregor Reid, Camilla Urbaniak, William L Byrne, Mark Tangney

Microbiology & Immunology Publications

In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs …

A Multi-Platform Metabolomics Approach Identifies Highly Specific Biomarkers Of Bacterial Diversity In The Vagina Of Pregnant And Non-Pregnant Women, Amy Mcmillan, Stephen Rulisa, Mark Sumarah, Jean M Macklaim, Justin Renaud, Jordan E Bisanz, Gregory B Gloor, Gregor Reid

Microbiology & Immunology Publications

Bacterial vaginosis (BV) increases transmission of HIV, enhances the risk of preterm labour, and is associated with malodour. Clinical diagnosis often relies on microscopy, which may not reflect the microbiota composition accurately. We use an untargeted metabolomics approach, whereby we normalize the weight of samples prior to analysis, to obtained precise measurements of metabolites in vaginal fluid. We identify biomarkers for BV with high sensitivity and specificity (AUC = 0.99) in a cohort of 131 pregnant and non-pregnant Rwandan women, and demonstrate that the vaginal metabolome is strongly associated with bacterial diversity. Metabolites associated with high diversity and clinical BV …

The Conserved G-Protein Coupled Receptor Fshr-1 Regulates Protective Host Responses To Infection And Oxidative Stress, Elizabeth V. Miller, Leah N. Grandi, Jennifer A. Giannini, Joseph D. Robinson, Jennifer R. Powell

Biology Faculty Publications

The innate immune system’s ability to sense an infection is critical so that it can rapidly respond if pathogenic microorganisms threaten the host, but otherwise maintain a quiescent baseline state to avoid causing damage to the host or to commensal microorganisms. One important mechanism for discriminating between pathogenic and non-pathogenic bacteria is the recognition of cellular damage caused by a pathogen during the course of infection. InCaenorhabditis elegans, the conserved G-protein coupled receptor FSHR-1 is an important constituent of the innate immune response. FSHR-1 activates the expression of antimicrobial infection response genes in infected worms and delays accumulation …

Winona Currents Magazine, University Advancement - Winona State University

Winona Currents

This magazine published by Winona State University’s University Advancement was intended to inform WSU Alumni, students, faculty, staff and the greater community about Alumni and the university. The cover theme is: Shine Bright Like a Warrior.

Development Of A Technology-Based Behavioral Vaccine To Prevent Adolescent Depression: A Health System Integration Model, Benjamin W. Van Voorhees, Tracy Gladstone, Stephanie Cordel, Monika Marko-Holguin, William Beardslee, Sachiko Kuwabara, Mark Allan Kaplan, Joshua Fogel, Anne Diehl, Chris Hansen, Carl Bell

Publications and Research

Efforts to prevent depression have become a key health system priority. Currently, there is a high prevalence of depression among adolescents, and treatment has become costly due to the recurrence patterns of the illness, impairment among patients, and the complex factors needed for a treatment to be effective. Primary care may be the optimal location to identify those at risk by offering an Internet-based preventive intervention to reduce costs and improve outcomes. Few practical interventions have been developed. The models for Internet intervention development that have been put forward focus primarily on the Internet component rather than how the program …

Corman Named 2015 Acp Laureate Winner, Kendra Carter

Browse All News

No abstract provided.

Design, Synthesis And Evaluation Of Bivalent Inhibitors Of Trehalose-6-Phosphate Phosphatase, Chunliang Liu

Chemistry and Chemical Biology ETDs

The D-glucose disaccharide α, α-D-trehalose is synthesized by a variety of bacteria, fungi, plants and invertebrates to support cell survival by functioning as a fuel, a metabolic regulator or a protectant against environmental stress. Five different trehalose biosynthetic pathways are known to exist, one of which, the OtsA/OtsB pathway is common among pathogenic bacteria and fungi and is also found in parasitic nematodes. Previously reported otsA and otsB gene knockout (or knockdown) experiments have shown that both pathway enzymes are essential for M. tuberculosis cell growth and host colonization. RNAi gene silencing carried out in the nematode model system Caenohabditis …

Characterization Of Electrophorectic Separations On A Cellulose Paper-Microfluidic Chip, Kyle Robert Fast

Master's Theses

The purpose of this thesis project is to demonstrate the ability to utilize electrophoresis in a cellulose paper microfluidic chip to manipulate charged particles. Materials were selected and a manufacturing protocol was created to successfully apply the electric field onto the paper chip. Experiments were performed to characterize the separation rates for charged, colorimetric dye, Orange G in the membrane as a function of an applied electric field, dye concentration, and distance traveled. The experiments confirmed that the electric field can be applied to the chip and particle separation rates were characterized. Next, the determined rates results were used to …

Herpes Simplex Vaccines: Prospects Of Live-Attenuated Hsv Vaccines To Combat Genital And Ocular Infections, Brent Stanfield, Konstantin Gus Kousoulas

Faculty Publications

© 2015, Springer International Publishing AG. Herpes simplex virus type 1 (HSV-1) and its closely related herpes simplex virus type 2 (HSV-2) cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in preclinical investigations with few progressing to early-phase clinical trials. Consensus research findings suggest that robust humoral …

Family Policy In Post-Communist Europe And The Former Soviet Union: Assessing The Impact Of Xenophobia, Marina A. Kingsbury

Political Science ETDs

This dissertation emphasizes the comparative aspect of family policy, with a regional focus on post-communist Europe. Following the turmoil of transition, many social welfare programs were transformed and often scaled back. Family policies, however, were largely carried through the initial period of transformation, despite the economic difficulties and the dramatic decline in birth rates in a course of several years. This study was inspired by the seeming contradiction between falling birth rates and increasing generosity of family policy provisions across the former communist European countries. This dissertation uses original data, which includes levels of benefit provision as well as national …

Per-Contact Infectivity Of Hcv Associated With Injection Exposures In A Prospective Cohort Of Young Injection Drug Users In San Francisco, Ca (Ufo Study), Yuridia Leyva

Mathematics & Statistics ETDs

Sharing needles and ancillary injection drug equipment places injection drug users (IDU) at risk for Hepatitis C Virus (HCV), a highly infectious blood-borne virus. A limited number of studies have analyzed the per-contact infectivity of HCV associated with the use of previously-used needles, but per-contact infectivity of ancillary injecting equipment has not been previously investigated. Our goal is to estimate the per-contact infectivity of HCV associated with (1) injecting with another person's previously-used needle, classified as receptive needle sharing (RNS), and (2) using another person's previously-used ancillary injecting equipment, such as cookers to melt drugs and cottons to strain impurities …

Maintenance Of Brucellosis In Yellowstone Bison: Linking Seasonal Food Resources, Host-Pathogen Interaction, And Life-History Trade-Offs, John J. Treanor, Chris Geremia, Michael A. Ballou, Duane H. Keisler, Patrick J. White, John J. Cox, Phillip H. Crowley

Biology Faculty Publications

The seasonal availability of food resources is an important factor shaping the life-history strategies of organisms. During times of nutritional restriction, physiological trade-offs can induce periods of immune suppression, thereby increasing susceptibility to infectious disease. Our goal was to provide a conceptual framework describing how the endemic level bovine brucellosis (Brucella abortus) may be maintained in Yellowstone bison based on the seasonality of food resources and the life-history strategies of the host and pathogen. Our analysis was based on active B. abortus infection (measured via bacterial culture), nutritional indicators (measured as metabolites and hormones in plasma), and carcass …

Streptococcal Throat: Therapeutic Options And Macrolide Resistance, Arif M. Al-Hamad

Saudi Medical Journal

No abstract provided.

Oncolog, Volume 60, Number 09, September 2015, Sarah Bronson, Bryan Tutt, K. Nair

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Enhanced Surgical Recovery Programs Improve Perioperative Outcomes for Cancer Patients: For patients undergoing cancer surgery, potential complications and long recovery times can delay the delivery of additional life-saving therapy. To improve patients' perioperative outcomes and clear the way for timely administration of additional therapies, several surgical teams at The University of Texas MD Anderson Cancer Center gave begun using enhanced surgical recovery programs (ESRPs).
• New Treatments for Respiratory Viruses in Immunocompromised Patients: Viral respiratory infections are a major concern for immunocompromised patients, in whom such infections are difficult to treat and can lead to pneumonia and even death. Although few …

Trim21 Regulates Nmi-Ifi35 Complex-Mediated Inhibition Of Innate Antiviral Response, Anshuman Das, Phat X. Dinh, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

In this study, using an immunoprecipitation coupled with mass spectrometry approach, we have identified the E3 ubiquitin ligase Trim21 as an interacting partner of IFI35 and Nmi. We found that this interaction leads to K63-linked ubiquitination on K22 residue of Nmi, but not IFI35. Using domain deletion analysis, we found that the interaction is mediated via the coiled-coil domain of Nmi and the carboxyl-terminal SPRY domain of Trim21. Furthermore, we show that depletion of Trim21 leads to significantly reduced interaction of Nmi with IFI35, which results in the abrogation of the negative regulatory function of the Nmi-IFI35 complex on innate …

Impact Of An Antimicrobial Stewardship Intervention On Urinary Tract Infection Treatment In The Emergency Department, Kelly M. Percival, Kristine M. Valenti, Stacy E. Scmittling, Brandi D. Strader, Rebecka R. Lopez, Scott Bergman

SIUE Faculty Research, Scholarship, and Creative Activity

STUDY OBJECTIVE:

The study objective is to assess changes in treatment of uncomplicated urinary tract infections (UTIs) after implementation of recommendations based on national guidelines and local resistance rates.

METHODS:

This preintervention and postintervention study included patients discharged home from the emergency department (ED) with an uncomplicated UTI at a 439-bed teaching hospital. Emergency department prescribers were educated on how local antimicrobial resistance rates impact UTI practice guidelines. Empiric treatment according to recommendations was assessed as the primary outcome. Agreement between chosen therapy and isolated pathogen susceptibility was compared before and after education. Reevaluation in the ED or hospital admission …

Recurrent Streptococcus Equi Subsp. Zooepidemicus Bacteremia In An Infant, Joshua R. Watson, Amy Leber, Sridhar Velineni, John F. Timoney, Monica I. Ardura

Maxwell H. Gluck Equine Research Center Faculty Publications

We describe a case of an infant with recurrent bacteremia caused by Streptococcus equi subsp. zooepidemicus, likely transmitted from mother to infant. Our case highlights the importance of an epidemiological history and molecular diagnostics in ascertaining insights into transmission, pathogenesis, and optimal management.

If You’Ve Seen One Worm, Have You Seen Them All? Spatial, Community, And Genetic Variability Of Tubificid Communities In Montana, Nilanjan Lodh, Donna M. Rizzo, Billie L. Kerans, Stephanie Mcginnis, Nikolaos Fytilis, Lori Stevens

Clinical Lab Sciences Faculty Research and Publications

Genetic studies are recognized increasingly as important for understanding naturally occurring disease dynamics and are used to predict host genetic diversity and coevolutionary processes and to identify species composition in ecological communities. Tubifex tubifex, the definitive host of the whirling disease parasite Myxobolus cerebralis, comprises 6 known lineages that vary widely in parasite susceptibility. We used 16S ribosomal DNA (16S rDNA) to identify relationships among genetic variability of 3 oligochaete genera (T. tubifex, Rhyacodrilus spp., and Ilyodrilus spp.; Oligochaeta:Tubificidae), oligochaete assemblage composition, and the presence of whirling disease in 9 locations across 4 watersheds in Montana, …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Vaccination Policies Of Utah Family Practice Clinics, Levi R. Kohler

Theses and Dissertations

The purpose of this study was to collect information regarding healthcare worker (HCW) vaccination policies in Utah family practice clinics. Data sources: The study was conducted in Utah family practice clinics in the most densely populated counties in the state and was a cross-sectional descriptive design. Data were collected from 155 family practice clinic managers. Analyses included frequencies and percentages for quantitative items and a content analysis for open-ended items. Conclusions: HCWs are employed in environments where infectious diseases can be easily spread from person to person, thus, vaccinations can be instrumental in protecting the health of HCWs and patients …