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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 …


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 …


Mc-Ppea As A New And More Potent Inhibitor Of Clp-Induced Sepsis And Pulmonary Inflammation Than Fk866., Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P. Heruth, Li Q. Zhang, Dev Maulik, Shui Qing Ye 2017 Children's Mercy Hospital

Mc-Ppea As A New And More Potent Inhibitor Of Clp-Induced Sepsis And Pulmonary Inflammation Than Fk866., Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P. Heruth, Li Q. Zhang, Dev Maulik, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Our previous study indicated that overexpression of nicotinamide phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced sepsis in C57BL/6J mice. MC4 showed stronger inhibitory effects than FK866 on CLP-induced mortality, serum tumor necrosis factor α (TNFα) levels, pulmonary myeloperoxidase activity, alveolar injury, and interleukin 6 and interleukin1β messenger …


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

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

Williams Honors College, 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 …


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 easily administered strategy. This …


Life-Threatening Hypercalcemia During Prodrome Of Pneumocystis Jiroveci Pneumonia In An Immunocompetent Infant, Judith Sebestyen VanSickle, Tarak Srivastava, Uri S. Alon 2017 Children's Mercy Hospital

Life-Threatening Hypercalcemia During Prodrome Of Pneumocystis Jiroveci Pneumonia In An Immunocompetent Infant, Judith Sebestyen Vansickle, Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Severe hypercalcemia in infants is usually attributed to genetic etiologies and less commonly to acquired ones. An 8-week-old girl presented with failure to thrive, mild respiratory distress, and life-threatening hypercalcemia (23.5 mg/dL). Serum 1,25(OH)2-D) level was elevated and parathyroid hormone undetectable. Evaluation for genetic mutations and malignant etiologies of hypercalcemia was negative. Treatment with intravenous hydration, loop diuretic, and calcitonin failed to correct the hypercalcemia, which was subsequently controlled with bisphosphonate therapy. Due to progressive respiratory deterioration, a bronchopulmonary lavage was done on day 17 of her hospitalization disclosing Pneumocystis jiroveci infection. The subsequent immunological investigation showed no abnormalities. She …


Orientia Tsutsugamushi Secretes Two Ankyrin Repeat-Containing Effectors Via A Type 1 Secretion System To Inhibit Host Nf-Κb Function, Sean M. Evans 2017 Virginia Commonwealth University

Orientia Tsutsugamushi Secretes Two Ankyrin Repeat-Containing Effectors Via A Type 1 Secretion System To Inhibit Host Nf-Κb Function, Sean M. Evans

Theses and Dissertations

Scrub typhus is a potentially fatal infection that threatens one billion persons in the Asia-Pacific region and is caused by the obligate intracellular bacterium, Orientia tsutsugamushi. How this organism facilitates its intracellular survival and pathogenesis is poorly understood. Intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) into the host cell to modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank libraries as well as Type 1 and Type 4 secretion systems (T1SS and T4SS), which are expressed during infection. In …


Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia McAuliffe 2016 Teagasc Food Research Centre, Fermoy, Ireland and Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Ireland

Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia Mcauliffe

Department of Biological Sciences Publications

The vast majority of clinical human listeriosis cases are caused by serotype 1/2a, 1/2b, 1/2c, and 4b isolates of Listeria monocytogenes. The ability of L. monocytogenes to establish a systemic listeriosis infection within a host organism relies on a combination of genes that are involved in cell recognition, internalization, evasion of host defenses, and in vitro survival and growth. Recently, whole genome sequencing and comparative genomic analysis have proven to be powerful tools for the identification of these virulence-associated genes in L. monocytogenes. In this study, two serotype 1/2b strains of L. monocytogenes with analogous isolation sources, but …


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 of gonococcal isolate resistance to current antimicrobials began …


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 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%) cases …


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 activity …


Intravenous Versus Oral Antibiotics For Postdischarge Treatment Of Complicated Pneumonia., Samir S. Shah, Rajendu Srivastava, Susan Wu, Jeffrey D. Colvin, Derek J. Williams, Shawn J. Rangel, Waheeda Samady, Suchitra Rao, Christopher Miller, Cynthia Cross, Caitlin Clohessy, Matthew Hall, Russell Localio, Matthew Bryan, Gong Wu, Ron Keren, Pediatric Research in Inpatient Settings Network 2016 Children's Mercy Hospital

Intravenous Versus Oral Antibiotics For Postdischarge Treatment Of Complicated Pneumonia., Samir S. Shah, Rajendu Srivastava, Susan Wu, Jeffrey D. Colvin, Derek J. Williams, Shawn J. Rangel, Waheeda Samady, Suchitra Rao, Christopher Miller, Cynthia Cross, Caitlin Clohessy, Matthew Hall, Russell Localio, Matthew Bryan, Gong Wu, Ron Keren, Pediatric Research In Inpatient Settings Network

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Postdischarge treatment of complicated pneumonia includes antibiotics administered intravenously via a peripherally inserted central venous catheter (PICC) or orally. Antibiotics administered via PICC, although effective, may result in serious complications. We compared the effectiveness and treatment-related complications of postdischarge antibiotics delivered by these 2 routes.

METHODS: This multicenter retrospective cohort study included children ≥2 months andadministration, classified as PICC or oral. The primary outcome was treatment failure. Secondary outcomes included PICC complications, adverse drug reactions, other related revisits, and a composite of all 4 outcomes, termed "all related revisits."

RESULTS: Among 2123 children, 281 (13.2%) received antibiotics …


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 …


Epidemiology And Impact Of Campylobacter Infection In Children In 8 Low-Resource Settings: Results From The Mal-Ed Study, Shahida Qureshi, Aneeta Hotwani, Sadia Shakoor, (MAL-ED) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Zulfiqar Ahmed Bhutta, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Anita K. M. Zaidi 2016 Aga Khan University

Epidemiology And Impact Of Campylobacter Infection In Children In 8 Low-Resource Settings: Results From The Mal-Ed Study, Shahida Qureshi, Aneeta Hotwani, Sadia Shakoor, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Zulfiqar Ahmed Bhutta, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life.
Methods: Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter Stool and blood samples were assayed for markers of intestinal permeability and inflammation.
Results: A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter We describe a high …


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 5-Year-Old With Fever, Headache, Neck Stiffness, And Leg Pain., Joy L. Solano, Grace Winningham, Duha Al Zubeidi, Angela Myers 2016 Children's Mercy Kansas City

A 5-Year-Old With Fever, Headache, Neck Stiffness, And Leg Pain., Joy L. Solano, Grace Winningham, Duha Al Zubeidi, Angela Myers

Manuscripts, Articles, Book Chapters and Other Papers

A 5-year-old boy presented with fever, headache, fatigue, neck stiffness, and 2 episodes of nocturnal urinary incontinence, prompting a visit to the emergency department. He had experienced intermittent frontal headaches and leg and buttock pain for several months, which had worsened over the previous 2 weeks. His history was notable for a spinal hemangioma with vascular tract, but he was otherwise healthy. On examination, he was febrile and tachycardic. He held his neck slightly rotated to the right with limited range of motion in all directions due to pain. No focal neurologic deficits were noted, and sensation and deep tendon …


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 …


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 IFN induction. We demonstrate that …


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