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University of Nebraska Medical Center

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Full-Text Articles in Medical Specialties

Sarcoidosis Of The Mandibular Condyle: A Rare Disease That Can Mimic Malignancy, Chad Sloan, Ben Lacrosse, Lei Yu, Alexander Braun, Scott Lauer, Timothy Donovan, John Baker, Jason Untrauer Dec 2019

Sarcoidosis Of The Mandibular Condyle: A Rare Disease That Can Mimic Malignancy, Chad Sloan, Ben Lacrosse, Lei Yu, Alexander Braun, Scott Lauer, Timothy Donovan, John Baker, Jason Untrauer

Graduate Medical Education Research Journal

Sarcoidosis can involve any of the organs, however intraosseous involvement is rare and ranges from 5 to 15%, with lesions of the mandible being even rarer – currently with few known cases reported. Intraosseous lesions involving the mandible have been noted to be asymptomatic or associated with chronic jaw pain. Additionally, mandibular involvement can present as a lytic bone lesion mimicking osseous malignancy. Chronic polyarthritis is commonly associated with the progression of sarcoidosis and intraosseous involvement has been considered a late-stage sequelae. We report a case of biopsy-proven sarcoidosis within the mandibular condyle in an asymptomatic 56-year-old Caucasian female who …


An Uncommon Adverse Effect Of A Common Drug-Dress Syndrome-Not Just Skin Deep!, Alamelu Udayappan Dec 2019

An Uncommon Adverse Effect Of A Common Drug-Dress Syndrome-Not Just Skin Deep!, Alamelu Udayappan

Graduate Medical Education Research Journal

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a rare, life-threatening hypersensitivity reaction that causes skin exfoliation, hematological abnormalities, lymphadenopathy, and extensive internal organ involvement. Characterized by a long latency period, this unusual side effect of aromatic anti-epileptic drugs, as well as many common drugs cause a mortality rate of up to 10% if left untreated. In the absence of a well-established therapy, primary and secondary prevention have a key role in the management of DRESS Syndrome. Herewith presenting a case of an adolescent girl with rashes and systemic symptoms, the cause of which, on obtaining a detailed …


The Financial Burden Of The Urology Match: Room For Improvement, Jinfeng Jiang, Joshua S. Engelsgjerd, Chad A. Lagrange, Christopher M. Deibert Dec 2019

The Financial Burden Of The Urology Match: Room For Improvement, Jinfeng Jiang, Joshua S. Engelsgjerd, Chad A. Lagrange, Christopher M. Deibert

Graduate Medical Education Research Journal

Abstract

Introduction/ Background – The Urology match remains highly competitive, but there is limited published data on the costs of the application process for contemporary applicants. This study aims to determine the financial burden of the Urological match and the effect it has on applicants.

Methods/ Materials – All applicants to the University of Nebraska Medical Center (UNMC) Urology Residency in the 2019 Urology match were invited to complete an anonymous, IRB approved online survey containing 16 questions on interview travel and costs, financial aid, and debt burden.

Results – Thirty-nine out of 183 (21%) applicants responded to the survey. …


An Overview Of Neurology Residency Training In Epilepsy At The University Of Nebraska Medical Center, Daniel Crespo Artunduaga, Mohamed Taha, Arun Swaminathan Dec 2019

An Overview Of Neurology Residency Training In Epilepsy At The University Of Nebraska Medical Center, Daniel Crespo Artunduaga, Mohamed Taha, Arun Swaminathan

Graduate Medical Education Research Journal

Neurology residency offers a comprehensive training program over 4 years in management of various neurological disorders. Epilepsy represents a common condition managed by neurologists and forms a core curriculum in the training of neurology residents. We conducted an anonymous survey among the trainees at our neurology program to identify knowledge and treatment gaps and help us modify our training regimens to provide high impact and good quality training to our trainees. We conducted a 35-question survey to determine various aspects of our neurology residents’ training to identify and overcome shortfalls. Our program requirements are rigorous and match up with those …


Long Term Outcomes Of Surgical And Clinical Symptoms Following Minimally Invasive Heller Myotomy: A Retrospective Clinical Database Review, Laura E. Flores, Priscila Rodrigues Armijo, Bhavani Pokala, Sarah Samreen, Dmitry Oleynikov Dec 2019

Long Term Outcomes Of Surgical And Clinical Symptoms Following Minimally Invasive Heller Myotomy: A Retrospective Clinical Database Review, Laura E. Flores, Priscila Rodrigues Armijo, Bhavani Pokala, Sarah Samreen, Dmitry Oleynikov

Graduate Medical Education Research Journal

I

Introduction

Minimally invasive Heller myotomy rates have increased, but little evidence is available regarding long term clinical and surgical outcomes. Our aim was to evaluate long term symptom improvement and medication resolution for patients undergoing minimally invasive Heller myotomy.

Methods

A single-institution database was retrospectively reviewed for patients undergoing laparoscopic Heller myotomy (LHM) or robotic Heller myotomy (RHM) during 2007-2018. Patients with primary HM followed by a Dor fundoplication were included. Demographics and surgical data were analyzed. Esophageal symptoms, testing, and medication use were collected preoperatively (pre-op), at 6-month (6-mo), 12-month (12-mo), and long-term (LT; 12-mo+) follow-up. Analysis was …


Necrotizing Enterocolitis Following Gastroschisis Repair: An Update, Rachel K. Schlueter, Shahab F. Abdessalam, Stephen C. Raynor, Robert A. Cusick Dec 2019

Necrotizing Enterocolitis Following Gastroschisis Repair: An Update, Rachel K. Schlueter, Shahab F. Abdessalam, Stephen C. Raynor, Robert A. Cusick

Graduate Medical Education Research Journal

Purpose:

Necrotizing enterocolitis (NEC) is a known complication of gastroschisis with an incidence above the expected rate in the neonatal population. While many physicians today are aware of this association, the last publication to explore this association in detail and identify possible risk factors of NEC in gastroschisis patients was published over twenty years ago. From our large database of patients with gastroschisis managed by a single group of pediatric surgeons, we reviewed our experience and the recent literature to update what is known about gastroschisis and NEC.

Methods:

From 2001 to 2017, a gastroschisis registry was maintained. Data from …


Association Between Gastroduodenal Ulcer And Age Of Diagnosis Of Head And Neck, Gastroduodenal And Pancreatic Cancer, Rukevwe Madusor Dec 2019

Association Between Gastroduodenal Ulcer And Age Of Diagnosis Of Head And Neck, Gastroduodenal And Pancreatic Cancer, Rukevwe Madusor

Capstone Experience: Master of Public Health

Background: Cancer is the second leading cause of death in the United States and remains a major public health problem worldwide. Epidemiological studies have demonstrated that insulin like growth factor-1 (IGF-1) is linked to ulcers and most cancers. Although studies have investigated the role of IGF1 in ulcer healing and cancer pathogenesis, the link between ulcer and cancer remains unclear. Hence, we assessed the relationship between ulcers and cancers.

Methods: This study consists of a sample of 180 cancer patients obtain by convenience sampling who were seen at Nebraska Medicine and were enrolled in the integrated cancer repository for cancer …


Examining Racial & Ethnic Disparities In The Reach Of The Medicare Shared Savings Program, Lindsey Arneson Dec 2019

Examining Racial & Ethnic Disparities In The Reach Of The Medicare Shared Savings Program, Lindsey Arneson

Capstone Experience: Master of Public Health

It is important to understand the quality of health care for racial and ethnic minorities covered under the largest U.S. government-run insurance program, Medicare, because the demographics of the U.S. are becoming older and more diverse. A new value-based program under Medicare is the Shared Savings Program (MSSP), which creates incentives to improve care quality and health outcomes for Medicare beneficiaries with a specific focus on increasing the provision of preventive care services. This capstone project aims to understand the representation of racial/ethnic minority Medicare beneficiaries, namely African Americans/Blacks and Hispanics/Latinxs, that receive care from providers or facilities (i.e., Accountable …


Following The Growth Of Sarah's Baby: An Ipe Activity For Medical Nutrition & Diagnostic Sonography Students, Tanya M. Custer, Megan Timmerman, Cynthia M. Schmidt, Teresa L. Hartman, Harlan Sayles, Kathryn Wampler, Lea Lambing, Kim Michael Aug 2019

Following The Growth Of Sarah's Baby: An Ipe Activity For Medical Nutrition & Diagnostic Sonography Students, Tanya M. Custer, Megan Timmerman, Cynthia M. Schmidt, Teresa L. Hartman, Harlan Sayles, Kathryn Wampler, Lea Lambing, Kim Michael

Posters and Presentations: Medical Imaging & Therapeutic Sciences

Objectives: Interprofessional education (IPE) involves collaborative learning among students from different professions. While acceptance of these types of activities is increasing, there are opportunities to expand the number of health care professions involved in IPE. The purpose of this study was to explore student perceptions and outcomes after participation in a Diagnostic Medical Sonography (DMS) and Medical Nutrition Education (MNE) interprofessional education activity centered around a clinical case study on fetal growth. Subjects & Methods: The IPE activity was administered to four student cohorts from academic years to 2015-2016 to 2018-2019. Participants included 66 students (n=39 DMS and n=27 MNE). …


Interoperable Knowledge Modeling In Emergency Care: Application Of The Hl7 Emergency Care Domain Analysis Model, James C. Mcclay, Laura Heermann Langford Jul 2019

Interoperable Knowledge Modeling In Emergency Care: Application Of The Hl7 Emergency Care Domain Analysis Model, James C. Mcclay, Laura Heermann Langford

Posters and Presentations: Emergency Medicine

The Emergency Care System (ECS) in the United States provides intermittent unscheduled care to an increasing number of patients annually. Every ECS patient encounter generates data in a myriad of unlinked systems at regional emergency services and hospitals. Often, their prior health records are not available in a timely manner, fragmented, or not found. To address availability and interoperability data relevant to emergency care, the Health Level Seven (HL7) Emergency Care Workgroup seeks to ensure evolving health data interoperability standards incorporate ECS considerations. Foundational to that effort is a comprehensive model of Emergency Care information. This emergency care domain analysis …


Relationship Between Binge Eating Disorder And Circadian Chronotype, Leon B. Jons May 2019

Relationship Between Binge Eating Disorder And Circadian Chronotype, Leon B. Jons

Theses & Dissertations

Binge eating disorder (BED) is a common condition in the general population and is more common in individuals with obesity. The later timing of food intake has been associated with an increase incidence of obesity. The purpose of this study was to evaluate the relationship between circadian chronotype and BED in a population of individuals with obesity. The sample consists of a retrospective review of 170 subjects presenting to an obesity medicine clinic who had been clinically evaluated for BED and chronotype.

No significant correlation was found between BED and a late chronotype in this population. In a secondary analysis …


Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad May 2019

Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad

Theses & Dissertations

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. However, maintenance of sustained plasma drug levels, for weeks or months, after a single high-level dosing, could improve regimen adherence but, at the same time, affect systemic toxicities. Of these, the most troubling are those that affect the central nervous system (CNS) In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal …


Evaluation Of The Role Of Microvascular Pathology On Peripheral Artery Disease, Constance Mietus May 2019

Evaluation Of The Role Of Microvascular Pathology On Peripheral Artery Disease, Constance Mietus

Theses & Dissertations

Background: Peripheral Artery Disease (PAD) begins with atherosclerotic narrowing of arteries, including those that supply the legs. Individuals with PAD experience pain during walking, which becomes increasingly limiting. Studies from our group and others have shown that a myopathy is present in the skeletal muscle of PAD patients, and is characterized by myofiber degeneration, fibrosis, and remodeling of vessels ranging from 50 – 150 mm in diameter. However, microvascular pathology, particularly of the smallest microvessels (5 – 15 mm in diameter) remains poorly characterized. Furthermore, little is known about the relationships between microvascular architecture, microperfusion, and patient walking performance. We …


The Role Of Ros In The Progression And Treatment Of Castration-Resistant Prostate Cancer, Dannah R. Miller May 2019

The Role Of Ros In The Progression And Treatment Of Castration-Resistant Prostate Cancer, Dannah R. Miller

Theses & Dissertations

Prostate cancer is the second leading cause of cancer-related deaths in U.S. men, primarily due to the development of castration-resistant (CR) prostate cancer (PCa), of which there are no effective treatment options. Reactive oxygen species (ROS) plays a critical role in prostate carcinogenesis, including the progression of the CR PCa phenotype. ROS regulates both cell proliferation and apoptosis; a moderate increase in ROS can promote proliferation; however, a substantial rise in ROS levels will result in apoptosis. Oxidase p66Shc is elevated in clinical PCa cells and has been associated with a metastatic phenotype of CR PCa cells, promoting PCa cell …


Mindful Meditation Practice For Imaging Professionals, Tanya M. Custer, Kim Michael Apr 2019

Mindful Meditation Practice For Imaging Professionals, Tanya M. Custer, Kim Michael

Posters and Presentations: Medical Imaging & Therapeutic Sciences

Although a career in medical imaging is very fulfilling and rewarding, research shows that health care professionals are becoming more prone to burnout. The healthcare environment can be face-paced, stressful and demanding. Burnout syndrome results from emotional exhaustion that causes depersonalization and decreased professional accomplishment.1-3 Burnout can have a negative impact not only on the individual, but the environment as well. Decreased patient satisfaction and increased errors are both associated with burnout in the healthcare setting.2

Mindfulness can be defined as the awareness that emerges through paying attention on purpose, in the present moment, and non-judgmentally to the unfolding of …


Improving Antimicrobial Stewardship Programs In Small Community Hospitals Through An Assessment And Feedback Model, Philip Chung, Kate Tyner, Scott Bergman, Terry Micheels, Mark Rupp, Michelle Schwedhelm, Maureen Tierney, Muhammad Salman Ashraf, Trevor Van Schooneveld Apr 2019

Improving Antimicrobial Stewardship Programs In Small Community Hospitals Through An Assessment And Feedback Model, Philip Chung, Kate Tyner, Scott Bergman, Terry Micheels, Mark Rupp, Michelle Schwedhelm, Maureen Tierney, Muhammad Salman Ashraf, Trevor Van Schooneveld

Posters and Presentations: Nebraska ASAP

Small community hospitals often lack expertise and resources for antimicrobial stewardship program implementation. Using an assessment-and-feedback model, Nebraska ASAP performed onsite assessment of antimicrobial stewardship efforts in 5 small community hospitals and provided facility specific feedback on implementation/augmentation of antimicrobial stewardship program. As a result of this model, participating small community hospitals were able to increase the number of antimicrobial stewardship core elements implemented while reducing antibiotic use and incidence of CDI.


Ovalbumin-Sensitized Mice Have Altered Airway Inflammation To Agriculture Organic Dust, Kristi J. Warren, John D. Dickinson, Amy J. Nelson, Todd A. Wyatt, Debra J. Romberger, Jill A. Poole Mar 2019

Ovalbumin-Sensitized Mice Have Altered Airway Inflammation To Agriculture Organic Dust, Kristi J. Warren, John D. Dickinson, Amy J. Nelson, Todd A. Wyatt, Debra J. Romberger, Jill A. Poole

Journal Articles: Internal Medicine

Agriculture exposures are associated with reducing the risk of allergy and asthma in early life; yet, repeated exposures later in life are associated with chronic bronchitis and obstructive pulmonary diseases. The objective of this study was to investigate the airway inflammatory response to organic dust extract (ODE) in mice with established ovalbumin (OVA)-induced experimental asthma. C57BL/6 mice were either OVA sensitized/aerosol-exposed or saline (Sal) sensitized/aerosol-challenged. Both groups were then subsequently challenged once with intranasal saline or swine confinement ODE to obtain 4 treatment groups of Sal-Sal, Sal-ODE, OVA-Sal, and OVA-ODE. Airway hyper-responsiveness (AHR) to methacholine, bronchiolar lavage fluid, lung tissues, …


Anti-Human Interleukin(Il)-4 Clone 8d4-8 Cross-Reacts With Myosin-9 Associated With Apoptotic Cells And Should Not Be Used For Flow Cytometry Applications Querying Il-4 Expression, Robert Z. Harms, Kiana Borengasser, Vikas Kumar, Nora Sarvetnick Jan 2019

Anti-Human Interleukin(Il)-4 Clone 8d4-8 Cross-Reacts With Myosin-9 Associated With Apoptotic Cells And Should Not Be Used For Flow Cytometry Applications Querying Il-4 Expression, Robert Z. Harms, Kiana Borengasser, Vikas Kumar, Nora Sarvetnick

Journal Articles: Surgery

Interleukin(IL)-4 is produced by T cells and other leukocytes and is a critical mediator of monocyte and B cell responses. During routine flow cytometry panel validation for the investigation of intracellular cytokines, we observed unique IL-4 expression patterns associated with the widely available monoclonal antibody 8D4-8. Namely, IL-4 (8D4-8) expression was observed in the absence of cellular activation and enhanced following staurosporine exposure. Mass spectrometry analysis of immunoprecipitates from peripheral blood lymphocytes (PBL) revealed that 8D4-8 cross-reacts with the ubiquitous cytoskeletal protein myosin-9. We confirmed these results by western blotting immunoprecipitates, using immunofluorescence among staurosporine-treated Caco-2 cells, and by surface-labeling …


The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang Jan 2019

The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. …


Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, Mckenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey Jan 2019

Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, Mckenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has been characterized as glucose depleted, indicating that peptides and free amino acids are an important source of nutrients for the bacteria. Our studies have found that mutations in enzymes necessary for growth on amino acids, including pyruvate carboxykinase (ΔpckA) and glutamate dehydrogenase (ΔgudB), reduced the ability of the bacteria to proliferate within a …


Identification Of Extracellular Dna-Binding Proteins In The Biofilm Matrix., Jeffrey S. Kavanaugh, Caralyn E. Flack, Jessica Lister, Erica B. Ricker, Carolyn B. Ibberson, Christian Jenul, Derek E. Moormeier, Elizabeth A. Delmain, Kenneth W. Bayles, Alexander R. Horswill Jan 2019

Identification Of Extracellular Dna-Binding Proteins In The Biofilm Matrix., Jeffrey S. Kavanaugh, Caralyn E. Flack, Jessica Lister, Erica B. Ricker, Carolyn B. Ibberson, Christian Jenul, Derek E. Moormeier, Elizabeth A. Delmain, Kenneth W. Bayles, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

We developed a new approach that couples Southwestern blotting and mass spectrometry to discover proteins that bind extracellular DNA (eDNA) in bacterial biofilms. Using Staphylococcus aureus as a model pathogen, we identified proteins with known DNA-binding activity and uncovered a series of lipoproteins with previously unrecognized DNA-binding activity. We demonstrated that expression of these lipoproteins results in an eDNA-dependent biofilm enhancement. Additionally, we found that while deletion of lipoproteins had a minimal impact on biofilm accumulation, these lipoprotein mutations increased biofilm porosity, suggesting that lipoproteins and their associated interactions contribute to biofilm structure. For one of the lipoproteins, SaeP, we …


Reanalysis Of The Nccn Pd-L1 Companion Diagnostic Assay Study For Lung Cancer In The Context Of Pd-L1 Expression Findings In Triple-Negative Breast Cancer, David L. Rimm, Gang Han, Janis M. Taube, Eunhee S. Yi, Julia A. Bridge, Douglas B. Flieder, Robert Homer, Anja C. Roden, Fred R. Hirsch, Ignacio I. Wistuba, Lajos Pusztai Jan 2019

Reanalysis Of The Nccn Pd-L1 Companion Diagnostic Assay Study For Lung Cancer In The Context Of Pd-L1 Expression Findings In Triple-Negative Breast Cancer, David L. Rimm, Gang Han, Janis M. Taube, Eunhee S. Yi, Julia A. Bridge, Douglas B. Flieder, Robert Homer, Anja C. Roden, Fred R. Hirsch, Ignacio I. Wistuba, Lajos Pusztai

Journal Articles: Pathology and Microbiology

The companion diagnostic test for checkpoint inhibitor immune therapy is an immunohistochemical test for PD-L1. The test has been shown to be reproducible for expression in tumor cells, but not in immune cells. Immune cells were used in the IMpassion130 trial which showed PD-L1 expression was associated with a better outcome. Two large studies have been done assessing immune cell PD-L1 expression in lung cancer. Here, we reanalyze one of those studies, to show that, even with an easier scoring method, there is still only poor agreement between assays and pathologist for immune cell PD-L1 expression.


Observations Of Shear Stress Effects On Staphylococcus Aureus Biofilm Formation, Erica Sherman, Kenneth W. Bayles, Derek E. Moormeier, Jennifer L. Endres, Timothy Wei Jan 2019

Observations Of Shear Stress Effects On Staphylococcus Aureus Biofilm Formation, Erica Sherman, Kenneth W. Bayles, Derek E. Moormeier, Jennifer L. Endres, Timothy Wei

Journal Articles: Pathology and Microbiology

Staphylococcus aureus bacteria form biofilms and distinctive microcolony or "tower" structures that facilitate their ability to tolerate antibiotic treatment and to spread within the human body. The formation of microcolonies, which break off, get carried downstream, and serve to initiate biofilms in other parts of the body, is of particular interest here. It is known that flow conditions play a role in the development, dispersion, and propagation of biofilms in general. The influence of flow on microcolony formation and, ultimately, what factors lead to microcolony development are, however, not well understood. The hypothesis being examined is that microcolony structures form …


Controlling Latent Tb Tuberculosis Infection In High-Burden Countries: A Neglected Strategy To End Tb, Gavin J. Churchyard, Susan Swindells Jan 2019

Controlling Latent Tb Tuberculosis Infection In High-Burden Countries: A Neglected Strategy To End Tb, Gavin J. Churchyard, Susan Swindells

Journal Articles: Infectious Diseases

In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries.


Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, Mckenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey Jan 2019

Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, Mckenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic …


Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A.C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Ching-Long Lin Jan 2019

Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A.C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.

METHODS: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, …


Tgf-Β Induces A Heart Failure Phenotype Via Fibroblasts Exosome Signaling, Hesham Basma, Adelaide N. Johanson, Kajari Dhar, Daniel R. Anderson, Fang Qiu, Stephen I. Rennard, Brian D. Lowes Jan 2019

Tgf-Β Induces A Heart Failure Phenotype Via Fibroblasts Exosome Signaling, Hesham Basma, Adelaide N. Johanson, Kajari Dhar, Daniel R. Anderson, Fang Qiu, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: The mechanisms for persistent and progressive loss of myocardial function in advanced heart failure (HF) remain incompletely characterized. In the current study, we sought to determine the impact of TGF-β on fibroblasts transcriptional profiles and assess if exosomes from TGF-β treated fibroblasts could induce a heart failure phenotype in co-cultured cardiomyocytes.

METHOD: Normal heart fibroblasts were treated with TGF-β with a final conc. of 2.5 ng/ml in serum free media. HF fibroblasts were also obtained from patients undergoing implantation of left ventricular assist devices. Exosomes were collected using three-step ultracentrifugation. Cardiomyocytes were co-cultured with exosomes from TGF-β-treated, HF and …


Bronchoalveolar Lavage Fluid From Copd Patients Reveals More Compounds Associated With Disease Than Matched Plasma, Eitan Halper-Stromberg, Lucas Gillenwater, Charmion Cruickshank-Quinn, Wanda Kay O'Neal, Nichole Reisdorph, Irina Petrache, Yonghua Zhuang, Wassim W. Labaki, Jeffrey L. Curtis, James Wells, Stephen I. Rennard, Katherine A. Pratte, Prescott Woodruff, Kathleen A. Stringer, Katerina Kechris, Russell P. Bowler Jan 2019

Bronchoalveolar Lavage Fluid From Copd Patients Reveals More Compounds Associated With Disease Than Matched Plasma, Eitan Halper-Stromberg, Lucas Gillenwater, Charmion Cruickshank-Quinn, Wanda Kay O'Neal, Nichole Reisdorph, Irina Petrache, Yonghua Zhuang, Wassim W. Labaki, Jeffrey L. Curtis, James Wells, Stephen I. Rennard, Katherine A. Pratte, Prescott Woodruff, Kathleen A. Stringer, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography-mass spectrometry (LC-MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected …


It's More Than Low Bmi: Prevalence Of Cachexia And Associated Mortality In Copd, Merry-Lynn N. Mcdonald, Emiel F.M. Wouters, Erica Rutten, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Marcas Bamman, Bartolome Celli, Alvar Agusti, Ruth Tal-Singer, Craig P. Hersh, Mark Dransfield, Edwin K. Silverman Jan 2019

It's More Than Low Bmi: Prevalence Of Cachexia And Associated Mortality In Copd, Merry-Lynn N. Mcdonald, Emiel F.M. Wouters, Erica Rutten, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Marcas Bamman, Bartolome Celli, Alvar Agusti, Ruth Tal-Singer, Craig P. Hersh, Mark Dransfield, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.

METHODS: In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The …


Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case Jan 2019

Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case

Journal Articles: Eppley Institute

While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O2-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O2- with no evident changes in hydrogen peroxide (H2O2), peroxynitrite (ONOO-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions …