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Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss,, Daniel R. Caffrey, Neal S. Silverman, Adam R. Wespiser, Catherine A. Hill 2016 Purdue University

Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss,, Daniel R. Caffrey, Neal S. Silverman, Adam R. Wespiser, Catherine A. Hill

Neal Silverman

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing approximately 57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing ...


Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang 2016 East Tennessee State University

Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang

Electronic Theses and Dissertations

Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.

The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia ...


Fecal Transplant Vs Vancomycin For Recurrent Clostridium Diffile, Lauren M. Taylor, Todd E. Edwards 2016 James Madison University

Fecal Transplant Vs Vancomycin For Recurrent Clostridium Diffile, Lauren M. Taylor, Todd E. Edwards

Physician Assistant Capstones

Objective: To compare fecal transplant and vancomycin in the treatment of recurrent clostridium difficile to determine which has the higher cure rate. Design: Systematic literature review. Methods: Pubmed, Google Scholar, and TRIP database using the search terms “recurrent clostridium difficile.” Filters were implemented in the Pubmed database including: randomized control trials, English, and published in the past 5 years. Records were screened for RCT with fecal transplant and full-text. Results: van Nood et al. revealed an initial cure rate of 81% for the infusion group, and a re-treated cure rate of 94%, compared to the vancomycin alone group of 31 ...


Investigation Of Cnt-Induced Escherichia Coli Lysis And Protein Release, Abdollah Mosleh 2016 University of Arkansas, Fayetteville

Investigation Of Cnt-Induced Escherichia Coli Lysis And Protein Release, Abdollah Mosleh

Theses and Dissertations

This research investigated the use of carbon nanotubes (CNTs) as a treatment to increase the permeability of a bacterial cell wall. Recombinant Escherichia coli BL21 (DE3) containing a plasmid that expressed Green Fluorescent Protein (GFP) and -lactamase were exposed to CNTs under various levels of agitation for different times. Fluorescence assay for GFP, optical absorbance for -lactamase activity, and Transmission Electron Microscopy (TEM) were used to determine the amount of released protein, and visually examine the permeability enhancement of the cells, respectively. It was found that more -lactamase was present in the culture fluid after treatment with CNTs in a ...


Comparisons Of Selected Household And Commercial Disinfectants Against Poultry Salmonella Isolates And A Survey Of Internal Parasites In Backyard Poultry In Arkansas, Kayleigh Moyle 2016 University of Arkansas, Fayetteville

Comparisons Of Selected Household And Commercial Disinfectants Against Poultry Salmonella Isolates And A Survey Of Internal Parasites In Backyard Poultry In Arkansas, Kayleigh Moyle

Theses and Dissertations

Backyard and exhibition poultry have been gaining in popularity and as such there has been a large increase in the number of small flocks. As the interaction with poultry has increased, so has the opportunity for diseases and parasites, for both birds and people. One of the major zoonotic illnesses is caused by the bacteria Salmonella, which can be found in commercial and small flocks. Salmonella is the number 2 contributor of foodborne illnesses so its prevalence in commercial flocks is of high concern. Despite improved cleaning, disinfection, and biosecurity practices, there is still potential for disease outbreaks and infections ...


Study Design Of A Cluster-Randomized Controlled Trial To Evaluate A Large-Scale Distribution Of Cook Stoves And Water Filters In Western Province, Rwanda, Corey L. Nagel, Miles Kirby, Laura D. Zambrano, Ghislaine Rosa, Christina K. Barstow, Evan A. Thomas, Thomas Clasen 2016 Oregon Health & Science University

Study Design Of A Cluster-Randomized Controlled Trial To Evaluate A Large-Scale Distribution Of Cook Stoves And Water Filters In Western Province, Rwanda, Corey L. Nagel, Miles Kirby, Laura D. Zambrano, Ghislaine Rosa, Christina K. Barstow, Evan A. Thomas, Thomas Clasen

Mechanical and Materials Engineering Faculty Publications and Presentations

Background: In Rwanda, pneumonia and diarrhea are the first and second leading causes of death, respectively, among children under five. Household air pollution (HAP) resultant from cooking indoors with biomass fuels on traditional stoves is a significant risk factor for pneumonia, while consumption of contaminated drinking water is a primary cause of diarrheal disease. To date, there have been no largescale effectiveness trials of programmatic efforts to provide either improved cookstoves or household water filters at scale in a low-income country. In this paper we describe the design of a clusterrandomized trial to evaluate the impact of a national-level program ...


Linezolid Induced Delirium In The Absence Of Serotonin Syndrome: A Psychiatric Consultation/Liaison Case Report, Hani Nazha, MD, Nathan T. Harrington, MD 2016 WVU

Linezolid Induced Delirium In The Absence Of Serotonin Syndrome: A Psychiatric Consultation/Liaison Case Report, Hani Nazha, Md, Nathan T. Harrington, Md

Marshall Journal of Medicine

Delirium is one of the most common mental illnesses that can affect elderly patients and patients with advanced medical problems. Because these patients are frequently on multiple medications and/or are more sensitive to medications secondary to their age, interactions with current medications, or existing medical problems; medication toxicity is frequently the etiology behind their delirium. This is a case report of a patient admitted for cellulitis that developed delirium from Linezolid however did not develop any other signs or symptoms of Serotonin Syndrome; a known side effect of Linezolid. This distinctive case highlights the importance of a careful analysis ...


Plague And The Defeat Of Mammalian Innate Immunity: Systematic Genetic Analysis Of Yersinia Pestis Virulence Factors: A Dissertation, Samantha G. Palace 2016 University of Massachusetts Medical School

Plague And The Defeat Of Mammalian Innate Immunity: Systematic Genetic Analysis Of Yersinia Pestis Virulence Factors: A Dissertation, Samantha G. Palace

GSBS Dissertations and Theses

Yersinia pestis, the causative agent of plague, specializes in causing dense bacteremia following intradermal deposition of a small number of bacteria by the bite of an infected flea. This robust invasiveness requires the ability to evade containment by the innate immune system. Of the various mechanisms employed by Y. pestis to subvert the innate immune response and to proliferate rapidly in mammalian tissue, only a few are well-characterized. Here, I present two complementary genetic analyses of Y. pestis adaptations to the mammalian environment. In the first, genome-wide fitness profiling for Y. pestis by Tn-seq demonstrates that the bacterium has adapted ...


Gram-Negative Bacteria And Sepsis, Christine D. Ridge 2016 Otterbein University

Gram-Negative Bacteria And Sepsis, Christine D. Ridge

Master of Science in Nursing (MSN) Student Scholarship

Today’s medical world encompasses an environment in which gram-negative bacteria that once were defeated with common antibiotics, have now become resistant. Gram-negative bacteria like Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter, and Acinetobacter are pathogens that are an emerging threat causing sepsis due to multidrug-resistance (Pop-Vicas & Opal, 2014, p.189). The multidrug-resistance mechanisms of gram-negative bacteria coupled with a patient population commonly seen in hospital settings, that consist of immunocompromised adults due to advancing age, comorbidities (e.g. AIDS, history of transplants, diabetes, and chemotherapy), and immunotherapies, create an environment for advanced infection or sepsis to take place.

Complications of multidrug-resistant ...


Memory Cd8+ T Cell Function During Mycobacterium Tuberculosis Infection: A Dissertation, Stephen M. Carpenter 2016 University of Massachusetts Medical School

Memory Cd8+ T Cell Function During Mycobacterium Tuberculosis Infection: A Dissertation, Stephen M. Carpenter

GSBS Dissertations and Theses

T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the ...


Type I Interferon Induction By Neisseria Gonorrhoeae: Dual Requirement Of Cyclic Gmp-Amp Synthase And Toll-Like Receptor 4, Warrison A. Andrade, Sarika Agarwal, Shunyan Mo, Scott A. Shaffer, Joseph P. Dillard, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Douglas T. Golenbock 2016 University of Massachusetts Medical School

Type I Interferon Induction By Neisseria Gonorrhoeae: Dual Requirement Of Cyclic Gmp-Amp Synthase And Toll-Like Receptor 4, Warrison A. Andrade, Sarika Agarwal, Shunyan Mo, Scott A. Shaffer, Joseph P. Dillard, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Douglas T. Golenbock

Open Access Articles

The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression. Here, we reveal a cytosolic response to GC DNA that also contributes to type I ...


Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu 2016 Chapman University

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review ...


Structural And Molecular Analysis Of A Protective Epitope Of Lyme Disease Antigen Ospa And Antibody Interactions, Shivender Shandilya, Nese Kurt Yilmaz, Ejemel Monir, Andrew Sadowski, William D. Thomas, Mark S. Klempner, Celia A. Schiffer, Yan Wang 2016 University of Massachusetts Medical School

Structural And Molecular Analysis Of A Protective Epitope Of Lyme Disease Antigen Ospa And Antibody Interactions, Shivender Shandilya, Nese Kurt Yilmaz, Ejemel Monir, Andrew Sadowski, William D. Thomas, Mark S. Klempner, Celia A. Schiffer, Yan Wang

UMass Center for Clinical and Translational Science Research Retreat

The murine monoclonal antibody LA-2 recognizes a clinically protective epitope on outer surface protein (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease in North America. Human antibody equivalence to LA-2 is the best serologic correlate of protective antibody responses following OspA vaccination. Understanding the structural and functional basis of the LA-2 protective epitope is important for developing OspA-based vaccines and discovering prophylactic antibodies against Lyme disease.

Here, we present a detailed structure-based analysis of the LA-2/OspA interaction interface and identification of residues mediating antibody recognition. Mutations were introduced into both OspA and LA-2 based on computational predictions ...


The Effect Of Oral Antibiotics On The Development Of Community Acquired Clostridium Difficile Colitis In Medicare Beneficiaries, Charles M. Psoinos, Courtney E. Collins, M. Didem Ayturk, Julie Flahive, Frederick A. Anderson Jr., Heena Santry 2016 University of Massachusetts Medical School

The Effect Of Oral Antibiotics On The Development Of Community Acquired Clostridium Difficile Colitis In Medicare Beneficiaries, Charles M. Psoinos, Courtney E. Collins, M. Didem Ayturk, Julie Flahive, Frederick A. Anderson Jr., Heena Santry

UMass Center for Clinical and Translational Science Research Retreat

Clostridium difficile infection (CDI) is increasingly prevalent among community dwelling Americans. Older Americans are particularly vulnerable to community-acquired Clostridium difficile (CACD), in part to increasing use of antibiotics. We studied the association between outpatient antibiotics and CACD among Medicare beneficiaries.

Case-control study utilizing a 5% sample of Medicare beneficiaries (2009-2011). Patients with CACD severe enough to warrant hospitalization were identified by a primary diagnosis code for CDI and no exposure to a healthcare environment within 90-days of admission. 1,514 CACD cases were matched to ten controls each on birth year and sex. Potential controls with exposure to healthcare environment ...


Identification Of Fully Human Monoclonal Antibodies Against The Adhesin Domain Of Colonizing Factor Antigen I Of Escherichia Coli, Maja Sedic, Danielle Wisheart, Monir Ejemel, Matteo Stoppato, Serena Giuntini, Eileen Barry, William D. Thomas, Mark S. Klempner, Yan Wang 2016 University of Massachusetts Medical School

Identification Of Fully Human Monoclonal Antibodies Against The Adhesin Domain Of Colonizing Factor Antigen I Of Escherichia Coli, Maja Sedic, Danielle Wisheart, Monir Ejemel, Matteo Stoppato, Serena Giuntini, Eileen Barry, William D. Thomas, Mark S. Klempner, Yan Wang

UMass Center for Clinical and Translational Science Research Retreat

Enterotoxigenic Escherichia coli (ETEC) causes significant diarrheal illness in infants in the developing world and travelers to endemic countries including military personnel. Infection of the host involves bacterial colonization of the small intestinal epithelium and toxin secretion leading to watery diarrhea. CFA/I is the most common colonizing factor antigens expressed on the surface of ETEC isolates. The CFA/I adhesin, CfaE, appears to be required for ETEC binding to human intestinal cells for colonization. Human antibodies against the binding domain of CfaE have potential to block colonization of ETEC and serve as a potent immunoprophylactic therapeutic for ETEC-related diarrhea ...


Immune Features That Afford Protection From Clinical Disease Versus Sterilizing Immunity To Bordetella Pertussis Infection In A Nonhuman Primate Model Of Whooping Cough, Keith A. Reimann, Aaron J. Belli, Sarah Fulco, Jason M. Warfel, Rijian Wang, Lisa Cavacini, James F. Papin, Steven F. Merkel, Tod J. Merkel, Mark S. Klempner 2016 University of Massachusetts Medical School

Immune Features That Afford Protection From Clinical Disease Versus Sterilizing Immunity To Bordetella Pertussis Infection In A Nonhuman Primate Model Of Whooping Cough, Keith A. Reimann, Aaron J. Belli, Sarah Fulco, Jason M. Warfel, Rijian Wang, Lisa Cavacini, James F. Papin, Steven F. Merkel, Tod J. Merkel, Mark S. Klempner

UMass Center for Clinical and Translational Science Research Retreat

The respiratory bacterial infection caused by Bordetella pertussis (whooping cough) is the only vaccine-preventable disease whose incidence has been increasing over the last 3 decades. To better understand the resurgence of this infection, a baboon animal model of pertussis infection has been developed. Naïve baboons that recover from experimental pertussis infection are resistant both to clinical disease and to airway colonization when re-challenged. In contrast, animals vaccinated with acellular pertussis vaccine and experimentally challenged do not develop disease, but airways remain colonized for 4-6 weeks. We explored the possibility that the IgG antibody response to pertussis infection is qualitatively different ...


Pre-Exposure Prophylaxis With Ospa-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission Of Lyme Disease Spirochetes, Yang Wang, Aurélie Kern, Naomi Boatright, Zachary Schiller, Andrew Sadowski, Monir Ejemel, Colby A. Souders, Keith A. Reimann, Linden Hu, William D. Thomas 2016 University of Massachusetts Medical School

Pre-Exposure Prophylaxis With Ospa-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission Of Lyme Disease Spirochetes, Yang Wang, Aurélie Kern, Naomi Boatright, Zachary Schiller, Andrew Sadowski, Monir Ejemel, Colby A. Souders, Keith A. Reimann, Linden Hu, William D. Thomas

UMass Center for Clinical and Translational Science Research Retreat

Background. Tick transmission of Borrelia spirochetes to humans results in significant morbidity from Lyme disease worldwide. Serum concentrations of antibodies against outer surface protein A (OspA) were shown to correlate with protection from infection with Borrelia burgdorferi, the primary cause of Lyme disease in the United States.

Methods. Mice transgenic for human immunoglobulin genes were immunized with OspA protein of B. burgdorferi to generate human monoclonal antibodies (HuMabs) against OspA. HuMabs were generated and tested in in vitro borreliacidal assays and animal protection assays.

Results. Nearly 100 unique OspA specific HuMabs were generated and four HuMabs (221-7, 857-2, 319-44, and ...


Activation And Inhibition Of Multiple Inflammasome Pathways By The Yersinia Pestis Type Three Secretion System: A Dissertation, Dmitry Ratner 2016 University of Massachusetts Medical School

Activation And Inhibition Of Multiple Inflammasome Pathways By The Yersinia Pestis Type Three Secretion System: A Dissertation, Dmitry Ratner

GSBS Dissertations and Theses

Host survival during plague, caused by the Gram-negative bacterium Yersinia pestis, is favored by a robust early innate immune response initiated by IL-1β and IL-18. Precursors of these cytokines are expressed downstream of TLR signaling and are then enzymatically processed into mature bioactive forms, typically by caspase-1 which is activated through a process dependent on multi-molecular structures called inflammasomes. Y. pestis evades immune detection in part by using a Type three secretion system (T3SS) to inject effector proteins (Yops) into host cells and suppress IL-1β and IL-18 production. We investigated the cooperation between two effectors, YopM and YopJ, in regulating ...


Clinical Approach To Nonresponsive Pneumonia In Adults Diagnosed By A Primary Care Clinician: A Retrospective Study, Kiley B. Vander Wyst, Jessica J. F. Kram, Dennis J. Baumgardner 2016 Center for Urban Population Health; Aurora Health Care

Clinical Approach To Nonresponsive Pneumonia In Adults Diagnosed By A Primary Care Clinician: A Retrospective Study, Kiley B. Vander Wyst, Jessica J. F. Kram, Dennis J. Baumgardner

Dennis J. Baumgardner. MD

Purpose

Community-acquired pneumonia (CAP) is commonly diagnosed in the primary care setting. Management of nonresponsive pneumonia (NRP), i.e. failure to respond to CAP treatment, is not clearly understood. The purpose of this study was to describe the initial work-up and treatment of CAP in the ambulatory primary care setting and to determine relative proportion of, diagnostic approach to and treatment of NRP.

Methods

We retrospectively studied adult patients diagnosed with CAP within our large, integrated health care system from October 2006 through July 2013. Cases were defined as patients with CAP who worsened after 4 days, or did not ...


Geographic Distribution Of Maternal Group B Streptococcus Colonization And Infant Death During Birth Hospitalization: Eastern Wisconsin, Jessica J. F. Kram, Dennis J. Baumgardner, Kiley B. Vander Wyst, Melissa A. Lemke 2016 Aurora Health Care

Geographic Distribution Of Maternal Group B Streptococcus Colonization And Infant Death During Birth Hospitalization: Eastern Wisconsin, Jessica J. F. Kram, Dennis J. Baumgardner, Kiley B. Vander Wyst, Melissa A. Lemke

Dennis J. Baumgardner. MD

Purpose

Maternal group B Streptococcus (GBS) can be transmitted from a colonized mother to newborn during vaginal delivery and may or may not contribute to infant death. This study aimed to explore the geographic distribution and risk factors of maternal GBS colonization and infant death during birth hospitalization.

Methods

We retrospectively studied mothers with live birth(s) in a large eastern Wisconsin hospital system from 2007 through 2013. Associations between maternal and neonatal variables, GBS colonization and infant death were examined using chi-squared, Mann-Whitney U and t-tests. Multivariable logistic regression models also were developed.

Results

Study population (N = 99,305 ...


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