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Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz 2017 University of Massachusetts Medical School

Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz

UMass Metabolic Network Publications

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with ...


Discovering A Novel Antifungal Target In Downstream Sterol Biosynthesis Using A Squalene Synthase Functional Motif, Kristin Brooke Linscott 2017 University of Kentucky

Discovering A Novel Antifungal Target In Downstream Sterol Biosynthesis Using A Squalene Synthase Functional Motif, Kristin Brooke Linscott

Theses and Dissertations--Molecular and Cellular Biochemistry

The sterol biosynthetic pathway is essential for growth of all eukaryotic cells and the main target of antifungal agents. The emergence of resistance to these antifungals in an already ill patient population indicates a need to develop drugs that have a broad spectrum of activity among pathogenic fungi and have minimal patient toxicity. Squalene synthase is the first committed step in the sterol pathway and has been studied intensively for development of antifungal agents. While the overall architecture of this enzyme is identical throughout eukaryotes, it was shown that plant and animal genes cannot complement a squalene synthase knockout mutation ...


Epidemiological Investigation Of Candida Species Causing Bloodstream Infection In Pediatric Small Bowel Transplant Recipients, Mallory J. Suhr, João Carlos Gomes-Neto, Nabaraj Banjara, Diana F. Florescu, David F. Mercer, Peter C. Iwen, Heather E. Hallen-Adams 2017 University of Nebraska-Lincoln

Epidemiological Investigation Of Candida Species Causing Bloodstream Infection In Pediatric Small Bowel Transplant Recipients, Mallory J. Suhr, João Carlos Gomes-Neto, Nabaraj Banjara, Diana F. Florescu, David F. Mercer, Peter C. Iwen, Heather E. Hallen-Adams

Faculty Publications in Food Science and Technology

Small bowel transplantation (SBT) can be a life-saving medical procedure. However, these recipients experience high risk of bloodstream infections caused by Candida. This research aims to characterize the SBT recipient gut microbiota over time following transplantation and investigate the epidemiology of candidemia in seven pediatric patients. Candida species from the recipients’ ileum and bloodstream were identified by internal transcribed spacer sequence and distinguished to strain by multilocus sequence typing and randomly amplified polymorphic DNA. Antifungal susceptibility of bloodstream isolates was determined against nine antifungals. Twenty-two ileostomy samples harbored at least one Candida species. Fungemia were caused by Candida parapsilosis, Candida ...


Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig 2017 Touro University California

Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig

College of Pharmacy (TUC) Publications and Research

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition of ...


Fluoride Varnish Application In The Pediatric Population, Ellen Gnaedinger 2017 University of Massachusetts Amherst

Fluoride Varnish Application In The Pediatric Population, Ellen Gnaedinger

Doctor of Nursing Practice (DNP) Projects

Purpose: The United States (U.S.) has a persistent problem of dental caries in primary teeth with a greater prevalence of dental caries found in minority and poor children. The majority of children in the U.S. experience dental caries in their primary teeth by age eight. This problem could be addressed by primary care providers applying fluoride varnish (FV) to children's teeth starting at the age of primary tooth eruption. The causes of dental caries in children’s primary teeth are multifactorial and therefore require multiple interventions. Around the world providers are utilizing FV as an effective and ...


Human Tear Fluid Reduces Culturability Of Contact Lens-Associated Pseudomonas Aeruginosa Biofilms But Induces Expression Of The Virulence-Associated Type Iii Secretion System, Yvonne T. Wu, Connie Tam, Lucia S. Zhu, David J. Evans, Suzanne M. J. Fleiszig 2017 Touro University California

Human Tear Fluid Reduces Culturability Of Contact Lens-Associated Pseudomonas Aeruginosa Biofilms But Induces Expression Of The Virulence-Associated Type Iii Secretion System, Yvonne T. Wu, Connie Tam, Lucia S. Zhu, David J. Evans, Suzanne M. J. Fleiszig

College of Pharmacy (TUC) Publications and Research

Purpose

The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens(CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression.

Methods

P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h. Biofilms were imaged using confocal microscopy. Bacterial culturability was quantified by viable counts, and T3SS gene expression measured by RT-qPCR ...


Biomarkers Of Sepsis: A Retrospective Approach, Jose M. Roberts 2017 The University of Akron

Biomarkers Of Sepsis: A Retrospective Approach, Jose M. Roberts

Honors Research Projects

Background: Biomarkers are taking the spotlight in becoming the norm for early diagnoses. Sepsis is an inflammatory disease that increases metabolic rate in children. The first biomarker is hyponatremia. Hyponatremia is a frequent electrolyte imbalance in clinical practice, often observed in children with inflammatory disease and infection. Presence of hyponatremia is associated with electrical signaling imbalances, inflammation and renal dysfunction. The clinical value of hyponatremia in pediatric patients is unknown. The C-reactive protein is a second biomarker. Its presence signifies that necrotic cells and inflammation are present.

Objectives: To evaluate the use of biomarkers in children seen in the Emergency ...


Determining The Effects Of Methanol, Ethanol, Isopropanol, And Glycerol On Both Thermal Stability And Catalytic Activity Of Rv0045c, An Enzyme From M. Tuberculosis, Katelyn Baumer 2017 Butler University

Determining The Effects Of Methanol, Ethanol, Isopropanol, And Glycerol On Both Thermal Stability And Catalytic Activity Of Rv0045c, An Enzyme From M. Tuberculosis, Katelyn Baumer

Undergraduate Honors Thesis Collection

Tuberculosis (TB) is a highly infectious respiratory disease contracted through the inhalation of Mycobacterium tuberculosis. Serine hydrolases are abundant in M. tuberculosis and serve as a model for studying the inhibition of TB. Rv0045c is an example of such with little known regarding its biological function. Rv0045c was exposed to methanol, ethanol, isopropanol, or glycerol and the effects of varying concentration of these alcohols on the catalytic efficiency and thermal stability of the enzyme was determined. The thermal stability of Rv0045c was found to decrease with concentration of methanol, ethanol, or isopropanol. The opposite was true of the thermal stability ...


Towards Shared Decision Making: Exploring New Ways Of Communicating Evidence To Patients About Benefits And Harms Of Antibiotics For Acute Respiratory Infections., Peter D. Coxeter 2017 Bond University

Towards Shared Decision Making: Exploring New Ways Of Communicating Evidence To Patients About Benefits And Harms Of Antibiotics For Acute Respiratory Infections., Peter D. Coxeter

Theses

Acute respiratory infections (ARIs) are one of the most common reasons for consultations in primary care and receiving an antibiotic, despite good evidence that they confer only marginal benefit and that these benefits may be outweighed by harms, as well as the potential contribution to antibiotic resistance. Antibiotic resistance is the ability of bacteria to naturally adapt to antibiotics used to treat them and reduces their effectiveness, and is now a global threat to public health. Potentially modifiable factors contributing to primary care prescribing of antibiotics for ARIs include diagnostic uncertainty, perceived and expressed patient expectations for an antibiotic, and ...


Performance Of The G4 Xpert(R) Mtb/Rif Assay For The Detection Of Mycobacterium Tuberculosis And Rifampin Resistance: A Retrospective Case-Control Study Of Analytical And Clinical Samples From High- And Low-Tuberculosis Prevalence Settings, Nila J. Dharan, Robert Blakemore, Alexander Sloutsky, Devinder Kaur, Richard C. Alexander, Minoo Ghajar, Kimberlee A. Musser, Vincent E. Escuyer, Marie-Claire Rowlinson, Susanne Crowe, Rafael Laniado-Laborin, Eloise Valli, Pamela Nabeta, Pamela Johnson, David Alland 2016 The State University of New Jersey

Performance Of The G4 Xpert(R) Mtb/Rif Assay For The Detection Of Mycobacterium Tuberculosis And Rifampin Resistance: A Retrospective Case-Control Study Of Analytical And Clinical Samples From High- And Low-Tuberculosis Prevalence Settings, Nila J. Dharan, Robert Blakemore, Alexander Sloutsky, Devinder Kaur, Richard C. Alexander, Minoo Ghajar, Kimberlee A. Musser, Vincent E. Escuyer, Marie-Claire Rowlinson, Susanne Crowe, Rafael Laniado-Laborin, Eloise Valli, Pamela Nabeta, Pamela Johnson, David Alland

Open Access Articles

BACKGROUND: The Xpert(R) MTB/RIF (Xpert) assay is a rapid PCR-based assay for the detection of Mycobacterium tuberculosis complex DNA (MTBc) and mutations associated with rifampin resistance (RIF). An updated version introduced in 2011, the G4 Xpert, included modifications to probe B and updated analytic software.

METHODS: An analytical study was performed to assess Xpert detection of mutations associated with rifampin resistance in rifampin-susceptible and -resistant isolates. A clinical study was performed in which specimens from US and non-US persons suspected of tuberculosis (TB) were tested to determine Xpert performance characteristics. All specimens underwent smear microscopy, mycobacterial culture, conventional ...


Geographical Incidence Of Antimicrobial Resistant Gonorrhea, Christofer A. Rodriguez 2016 University of San Francisco

Geographical Incidence Of Antimicrobial Resistant Gonorrhea, Christofer A. Rodriguez

Master's Projects and Capstones

Evolving throughout the last century, Gonorrhea has become a superbug, becoming difficult to treat. As the second most commonly reported notifiable disease, gonorrhea rates have been increasing, despite efforts in prevention and treatment. Populations at risk are mainly MSM and FSW. In 2015, men’s gonorrhea rates in the United States were higher compared to women, at 140.9 and 107.2 per 100,000 population, respectively. Illinois has consecutively had higher rates of infection compared to the US, at 133.5 per 100,000 population compared to the US rate of 123.9 per 100,000 population. The surveillance ...


Xpert Mtb/Rif Assay Shows Faster Clearance Of Mycobacterium Tuberculosis Dna With Higher Levels Of Rifapentine Exposure., A Jayakumar, R M Savic, C K Everett, Debra Benator, D Alland, C M Heilig, M Weiner, S O Friedrich, N A Martinson, A Kerrigan, C Zamudio, S V Goldberg, W C Whitworth, J L Davis, P Nahid 2016 George Washington University

Xpert Mtb/Rif Assay Shows Faster Clearance Of Mycobacterium Tuberculosis Dna With Higher Levels Of Rifapentine Exposure., A Jayakumar, R M Savic, C K Everett, Debra Benator, D Alland, C M Heilig, M Weiner, S O Friedrich, N A Martinson, A Kerrigan, C Zamudio, S V Goldberg, W C Whitworth, J L Davis, P Nahid

Medicine Faculty Publications

The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert CT trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial ...


Cost Of Care For Hospitalized Patients With Pulmonary Mycobacterial Diseases In The United States., Mary Beth Wells Allen 2016 University of Louisville

Cost Of Care For Hospitalized Patients With Pulmonary Mycobacterial Diseases In The United States., Mary Beth Wells Allen

Electronic Theses and Dissertations

Background: Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). Few data are available measuring the cost burden of mycobacterial diseases on the national level. The purpose of this study was to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM in the US from 2001 through 2012. Methods: This study was a retrospective community based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of ...


Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 additional authors 2016 George Washington University

Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 Additional Authors

Epidemiology and Biostatistics Faculty Publications

BACKGROUND:  Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.

METHODS:  Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.

RESULTS:  Bordetella pertussis was detected in 53 of 4200 (1.3 ...


Tb Screening Guidelines For Transitional Care Unit, Caleb E. Newcomer 2016 Murray State University

Tb Screening Guidelines For Transitional Care Unit, Caleb E. Newcomer

Scholars Week

The basis of this research was the formation of new TB screening and risk assessment guidelines on a Transitional Care Unit within a medical center. Current evidence-based research studies helped to guide the recommendations for the policy changes based on their results and findings. The most pertinent policy changes are the treatment offered for patients suspected with HIV, the rigorous use of the Risk Assessment Tool, and BAMT testing for TB.


Path To Resistance: Risk Factors Associated With Carbapenem-Resistant Pseudomonas Aeruginosa, Kushal Patel, Jessica J.F. Kram, Dennis J. Baumgardner 2016 Department of Internal Medicine, Aurora Sinai Medical Center

Path To Resistance: Risk Factors Associated With Carbapenem-Resistant Pseudomonas Aeruginosa, Kushal Patel, Jessica J.F. Kram, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Background: An estimated 51,000 health care-associated Pseudomonas aeruginosa infections occur in the United States annually. More than 13% are secondary to non-carbapenem multidrug-resistant strains, which result in 400 yearly deaths. Traditional risk factors for resistance include ICU stay, mechanical ventilation, previous hospitalization and major comorbidities. As microbes evolve, risk factors also may evolve.

Purpose: To determine if traditional and/or new risk factors for P. aeruginosa resistance are valid and predictive of infection with carbapenem-resistant P. aeruginosa.

Methods: We retrospectively studied inpatients and outpatients ≥ 18 years old who presented to an Aurora Health Care facility with a positive P ...


Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, Maria J. Gutierrez, Neelu Kaira, Alexandra Horwitz, Gustavo Nino 2016 George Washington University

Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, Maria J. Gutierrez, Neelu Kaira, Alexandra Horwitz, Gustavo Nino

Pediatrics Faculty Publications

Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that (a ...


When It Isn’T Always Lyme: Expanding The Differential Diagnosis For Acute-Onset Polyarthralgia In The West Virginia Eastern Panhandle, Natalie A. Moffett, Rosemarie Lorenzetti 2016 West Virginia University

When It Isn’T Always Lyme: Expanding The Differential Diagnosis For Acute-Onset Polyarthralgia In The West Virginia Eastern Panhandle, Natalie A. Moffett, Rosemarie Lorenzetti

Marshall Journal of Medicine

This case presentation discusses a 36 year-old female animal care worker presenting with an acute-onset polyarthropathy during the summer months in a Lyme endemic region. Though she appeared to be a good candidate for the diagnosis of Lyme borreliosis, her screening serology reported negative results and alternative diagnoses were considered. Her subsequent diagnosis with parvovirus B19 acts to remind the general practitioner to have confidence in the accuracy of a negative Lyme screen and, upon negative result, to expand the differential to include less common infections including parvovirus B19. It also highlights the need to remember parvovirus B19 in a ...


Distinct Surveillance Pathway For Immunopathology During Acute Infection Via Autophagy And Sr-Bi, Susanne Pfeiler, Eicke Latz, Bernd Engelmann 2016 Ludwig-Maximilians-Universitat

Distinct Surveillance Pathway For Immunopathology During Acute Infection Via Autophagy And Sr-Bi, Susanne Pfeiler, Eicke Latz, Bernd Engelmann

Open Access Articles

The mechanisms protecting from immunopathology during acute bacterial infections are incompletely known. We found that in response to apoptotic immune cells and live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti-atherogenic lipid exchange mediator, activated internalization mechanisms with characteristics of macropinocytosis and, assisted by Golgi fragmentation, initiated autophagic responses. This was supported by scavenger receptor-induced local increases in membrane cholesterol concentrations which generated lipid domains particularly in cell extensions and the Golgi. SR-BI was a key driver of beclin-1-dependent autophagy during acute bacterial infection of the liver and spleen. Autophagy regulated tissue infiltration of neutrophils, suppressed accumulation of ...


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

Katherine A. Fitzgerald

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 ...


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