Anatomy Commons^™

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Latent Traits Of Lung Tissue Patterns In Former Smokers Derived By Dual Channel Deep Learning In Computed Tomography Images, Frank Li, Jiwoong Choi, Chunrui Zou, John D. Newell, Alejandro P. Comellas, Chang Hyun Lee, Hongseok Ko, R. Graham Barr, Eugene R. Bleecker, Christopher B. Cooper, Fereidoun Abtin, Igor Barjaktarevic, David Couper, Meilan Han, Nadia N. Hansel, Richard E. Kanner, Robert Paine, Ella A. Kazerooni, Fernando J. Martinez, Wanda O'Neal, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Eric A. Hoffman, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and the traditional variables extracted from computed tomography (CT) images may not be sufficient to describe all the topological features of lung tissues in COPD patients. We employed an unsupervised three-dimensional (3D) convolutional autoencoder (CAE)-feature constructor (FC) deep learning network to learn from CT data and derive tissue pattern-clusters jointly. We then applied exploratory factor analysis (EFA) to discover the unobserved latent traits (factors) among pattern-clusters. CT images at total lung capacity (TLC) and residual volume (RV) of 541 former smokers and 59 healthy non-smokers from the cohort of the SubPopulations …

Small Airway Determinants Of Airflow Limitation In Chronic Obstructive Pulmonary Disease, Vasiliy V. Polosukhin, Sergey S. Gutor, Rui-Hong Du, Bradley W. Richmond, Pierre P. Massion, Pingsheng Wu, Justin M. Cates, Kim L. Sandler, Stephen I. Rennard, Timothy S. Blackwell

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Although a variety of pathological changes have been described in small airways of patients with COPD, the critical anatomic features determining airflow limitation remain incompletely characterised.

METHODS: We examined lung tissue specimens from 18 non-smokers without chronic lung disease and 55 former smokers with COPD for pathological features of small airways that could contribute to airflow limitation. Morphometric evaluation was performed for epithelial and subepithelial tissue thickness, collagen and elastin content, luminal mucus and radial alveolar attachments. Immune/inflammatory cells were enumerated in airway walls. Quantitative emphysema scoring was performed on chest CT scans.

RESULTS: Small airways from patients with …

Genetic Variation In Genes Regulating Skeletal Muscle Regeneration And Tissue Remodelling Associated With Weight Loss In Chronic Obstructive Pulmonary Disease, Preeti Lakshman Kumar, Ava C. Wilson, Alison Rocco, Michael H. Cho, Emily Wan, Brian D. Hobbs, George R. Washko, Victor E. Ortega, Stephanie A. Christenson, Xingnan Li, J. Michael Wells, Surya P. Bhatt, Dawn L. Demeo, Sharon M. Lutz, Harry Rossiter, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Wassim W. Labaki, Ruth Tal-Singer, Russel P. Bowler, Craig P. Hersh, Hemant K. Tiwari, Mark Dransfield, Anna Thalacker-Mercer, Deborah A. Meyers, Edwin K. Silverman, Merry-Lynn N. Mcdonald, Copdgene, Eclipse And Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach.

METHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low …

The Effect Of Long-Acting Dual Bronchodilator Therapy On Exercise Tolerance, Dynamic Hyperinflation, And Dead Space During Constant Work Rate Exercise In Copd, William W. Stringer, Janos Porszasz, Min Cao, Harry B. Rossiter, Shahid Siddiqui, Stephen I. Rennard, Richard Casaburi

Journal Articles: Pulmonary & Critical Care Med

We investigated whether dual bronchodilator therapy (glycopyrrolate/formoterol fumarate; GFF; Bevespi Aerosphere) would increase exercise tolerance during a high-intensity constant work rate exercise test (CWRET) and the relative contributions of dead space ventilation (V_D/V_T) and dynamic hyperinflation (change in inspiratory capacity) to exercise limitation in chronic obstructive pulmonary disease (COPD). In all, 48 patients with COPD (62.9 ± 7.6 yrs; 33 male; GOLD spirometry stage 1/2/3/4, n = 2/35/11/0) performed a randomized, double blind, placebo (PL) controlled, two-period crossover, single-center trial. Gas exchange and inspiratory capacity (IC) were assessed during cycle ergometry at 80% incremental exercise peak …

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

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data.

PATIENTS AND METHODS: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit. A total of 150 qCT imaging-based variables, comprising 75 variables at baseline and their corresponding progression rates, were derived from the respective inspiration and expiration scans of the two visits. The COPD progression clusters identified were then associated with subject demography, clinical variables and biomarkers.

RESULTS: COPD severities at baseline …

Endoscopic Removal Of Fractured 3d-Printed Nasopharyngeal Swabs From The Olfactory Cleft During Covid-19, Matthew Miller, Kristy Carlson, Jayme Dowdall, Christie Barnes, Sam Pate

Graduate Medical Education Research Journal

The severe acute respiratory syndrome SARS-CoV-2 pandemic has posed significant challenges to hospital and public health systems in the United States. In response to a shortage in nasopharyngeal swabs, our institution developed, tested, and deployed 3D-printed swabs to obtain a specimen for testing. A patient was tested in preparation for a scheduled Esophagogastrodeuodenoscopy. During the procedure the swab broke and a portion remained in the superior meatus and olfactory cleft. This case study describes the process of locating and removing the broken sections of the 3D-printed swab. In response to this incident, 3D-printing teams test swabs for sample collection and …

Current Smoking With Or Without Chronic Bronchitis Is Independently Associated With Goblet Cell Hyperplasia In Healthy Smokers And Copd Subjects, Victor Kim, Stephanie Jeong, Huaqing Zhao, Mehmet Kesimer, Richard C. Boucher, J. Michael Wells, Stephanie A. Christenson, Meilan K. Han, Mark Dransfield, Robert Paine, Christopher B. Cooper, Igor Barjaktarevic, Russell Bowler, Jeffrey L. Curtis, Robert J. Kaner, Sarah L. O'Beirne, Wanda K. O'Neal, Stephen I. Rennard, Fernando J. Martinez, Prescott G. Woodruff

Journal Articles: Pulmonary & Critical Care Med

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, …

Co-Morbidity Patterns Identified Using Latent Class Analysis Of Medications Predict All-Cause Mortality Independent Of Other Known Risk Factors: The Copdgene® Study, Yisha Li, Margaret Ragland, Erin Austin, Kendra Young, Katherine Pratte, John E. Hokanson, Terri H Beaty, Elizabeth A. Regan, Stephen I. Rennard, Christina Wern, Michael R. Jacobs, Ruth Tal-Singer, Barry J. Make, Gregory L. Kinney, Copdgene Investigators

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Medication patterns include all medications in an individual's clinical profile. We aimed to identify chronic co-morbidity treatment patterns through medication use among COPDGene participants and determine whether these patterns were associated with mortality, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and quality of life.

MATERIALS AND METHODS: Participants analyzed here completed Phase 1 (P1) and/or Phase 2 (P2) of COPDGene. Latent class analysis (LCA) was used to identify medication patterns and assign individuals into unobserved LCA classes. Mortality, AECOPD, and the St. George's Respiratory Questionnaire (SGRQ) health status were compared in different LCA classes through survival analysis, logistic …

Blood Eosinophil Counts In Clinical Trials For Chronic Obstructive Pulmonary Disease, Dave Singh, Mona Bafadhel, Christopher E. Brightling, Frank C. Sciurba, Jeffrey L. Curtis, Fernando J. Martinez, Cara B. Pasquale, Debora D. Merrill, Norbert Metzdorf, Stefano Petruzzelli, Ruth Tal-Singer, Christopher Compton, Stephen I. Rennard, Ubaldo J. Martin

Journal Articles: Pulmonary & Critical Care Med

No abstract provided.

Heme Metabolism Genes Downregulated In Copd Cachexia, Ava C. Wilson, Preeti L. Kumar, Sool Lee, Margaret M. Parker, Itika Arora, Jarrett D. Morrow, Emiel F.M. Wouters, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Alvar Agusti, Ruth Tal-Singer, Mark T. Dransfield, J. Michael Wells, Surya P. Bhatt, George Washko, Victor J. Thannickal, Hemant K. Tiwari, Craig P. Hersh, Peter J. Castaldi, Edwin K. Silverman, Merry-Lynn N. Mcdonald

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Cachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.

METHODS: We analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (<  20 kg/m

RESULTS: The prevalence of …

Improving The Evaluation Of Copd Exacerbation Treatment Effects By Accounting For Early Treatment Discontinuations: A Post-Hoc Analysis Of Randomized Clinical Trials., Agnieszka Król, Robert Palmér, Virginie Rondeau, Stephen I. Rennard, Ulf G. Eriksson, Alexandra Jauhiainen

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) clinical trials aimed at evaluating treatment effects on exacerbations often suffer from early discontinuations of randomized treatment. Treatment discontinuations imply a loss of information and should ideally be considered in the statistical analysis of trial results, particularly if the discontinuations are related to the disease or treatment itself. Here, we explore this issue by investigating (1) whether there exists an association between the risks of exacerbation and treatment discontinuation in COPD clinical trials and (2) whether disregarding this association can cause bias in exacerbation treatment effect estimates. We focus on the hypothetical estimand, i.e. …

Agonist-Specific Desensitization Of Pge2-Stimulated Camp Signaling Due To Upregulated Phosphodiesterase Expression In Human Lung Fibroblasts, Francisco J. Nunez, Nancy Schulte, David M. Fogel, Joel Michalski, Stephen I. Rennard, Raymond B. Penn, Myron L. Toews, Rennolds S. Ostrom

Journal Articles: Pulmonary & Critical Care Med

Pulmonary fibrosis is characterized by fibroblasts persisting in an activated form, producing excessive fibrous material that destroys alveolar structure. The second messenger molecule cyclic 3',5'-adenosine monophosphate (cAMP) has antifibrotic properties, and prostaglandin E2 (PGE2) can stimulate cAMP production through prostaglandin E (EP)2 and EP4 receptors. Although EP receptors are attractive therapeutic targets, the effects of long-term exposure to PGE2 have not been characterized. To determine the effects of long-term exposure of lung fibroblasts to PGE2, human fetal lung (HFL)-1 cells were treated for 24 h with 100 nM PGE2 or other cAMP-elevating agents. cAMP levels stimulated by acute exposure to …

Prostaglandins And Kidney Function: A Comparison Between The Cortical And Inner Medullary Collecting Duct On Prostaglandin Production, Dane N. Wilson

Theses & Dissertations

Prostaglandins are paracrine and autocrine signaling molecules that play important roles through various physiological and pathophysiological functions in the human body including the inflammatory response, control of blood pressure, and water and salt homeostasis in the kidney. Prostaglandins have been shown to have great influence on kidney function. In particular, prostaglandin E₂ influences the function of the collecting duct, primarily decreasing vasopressin-stimulated collecting duct water permeability. The aim of this study was to see how various treatments to cells, as well as different growth times, impacted prostaglandin production between two different collecting duct cell lines, one arising from the …

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

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

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 …

Prospective Observational Study In Patients With Obstructive Lung Disease: Novelty Design, Helen K. Reddel, Maria Gerhardsson De Verdier, Alvar Agustí, Gary Anderson, Richard Beasley, Elisabeth H. Bel, Christer Janson, Barry Make, Richard J. Martin, Ian Pavord, David Price, Christina Keen, Asparuh Gardev, Stephen I. Rennard, Alecka Sveréus, Aruna T. Bansal, Lance Brannman, Niklas Karlsson, Javier Nuevo, Fredrik Nyberg, Simon S. Young, Jørgen Vestbo

Journal Articles: Pulmonary & Critical Care Med

Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY …

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, …

Imaging-Based Clusters In Current 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, 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, Stephen I. Rennard, Prescott G. Woodruff, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations. Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.

METHODS: Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers. Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%). Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter. We employed an unsupervised method for clustering.

RESULTS: Four clusters …

Use Of A 4-Week Up-Titration Regimen Of Roflumilast In Patients With Severe Copd, Henrik Watz, Nitin Bagul, Klaus F. Rabe, Stephen I. Rennard, Vijay Kt Alagappan, Jonas Román, Axel Facius, Peter Ma Calverley

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The oral selective phosphodiesterase-4 inhibitor roflumilast (ROF) reduces exacerbations in patients with severe COPD. Adverse events (AEs) can cause early ROF discontinuation. Alternative dosing strategies may help patients continue their therapy.

METHODS: In this multicenter, double-blind trial, 1,321 patients with severe COPD were randomized 1:1:1 to 4 weeks' treatment with ROF 250 µg once daily (OD), 500 µg every other day (EOD), or 500 µg OD, each followed by ROF 500 µg OD for 8 weeks, plus standard therapy. The primary end point was the percentage of patients prematurely discontinuing study treatment.

RESULTS: Patients in the 250 µg OD/500 …

Centrilobular Emphysema And Coronary Artery Calcification: Mediation Analysis In The Spiromics Cohort, Surya P. Bhatt, Hrudaya P. Nath, Young-Il Kim, Rekha Ramachandran, Jubal R. Watts, Nina L.J. Terry, Sushil Sonavane, Swati P. Deshmane, Prescott G. Woodruff, Elizabeth C. Oelsner, Sandeep Bodduluri, Meilan K. Han, Wassim W. Labaki, J. Michael Wells, Fernando J. Martinez, R. Graham Barr, Mark T. Dransfield, Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established.

METHODS: We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used …

Can Capture Be Used To Identify Undiagnosed Patients With Mild-To-Moderate Copd Likely To Benefit From Treatment?, Nancy K. Leidy, Fernando J. Martinez, Karen G. Malley, David M. Mannino, Meilan K. Han, Elizabeth D. Bacci, Randall W. Brown, Julia F. Houfek, Wassim W. Labaki, Barry J. Make, Catherine A. Meldrum, Wilson Quezada, Stephen I. Rennard, Byron Thomashow, Barbara P. Yawn

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV

METHODS: Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were also estimated. The modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT™) …

The Development Of Azd7624 For Prevention Of Exacerbations In Copd: A Randomized Controlled Trial, Naimish R. Patel, Danen M. Cunoosamy, Malin Fagerås, Ziad Taib, Sara Asimus, Tove Hegelund-Myrbäck, Sofia Lundin, Katerina Pardali, Nisha Kurian, Eva Ersdal, Cecilia Kristensson, Katarina Korsback, Robert Palmér, Mary N. Brown, Steven Greenaway, Leonard Siew, Graham W. Clarke, Stephen I. Rennard, Barry J. Make, Robert A. Wise, Paul Jansson

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: p38 mitogen-activated protein kinase (MAPK) plays a central role in the regulation and activation of pro-inflammatory mediators. COPD patients have increased levels of activated p38 MAPK, which correlate with increased lung function impairment, alveolar wall inflammation, and COPD exacerbations.

OBJECTIVES: These studies aimed to assess the effect of p38 inhibition with AZD7624 in healthy volunteers and patients with COPD. The principal hypothesis was that decreasing lung inflammation via inhibition of p38α would reduce exacerbations and improve quality of life for COPD patients at high risk for acute exacerbations.

METHODS: The p38 isoform most relevant to lung inflammation was assessed …

Understanding The Chondrogenic Potential Of Articular Chondrocytes, Krishna Sarma

Theses & Dissertations

Articular cartilage is a smooth, visco-elastic, aneural, avascular tissue made of water, an exquisitely organized framework of proteoglycans, glycosaminoglycans, and collagen fibrils and articular chondrocytes. It’s beautiful organization and composition provide it with the flexibility and strength to cover, protect and lubricate the ends of long bones in a diarthrodial joint. Cartilage homeostasis relies on articular chondrocytes to translate the mechanical forces of daily activity into efficient remodeling of the extracellular matrix. Age, joint injury, or other insulting factors can progressively incapacitate articular chondrocytes, resulting in cartilage lesions that devolve to degenerative joint disease. Therefore, the central idea explored in …

A Cadaveric Study Of Coronary Artery Variations, Mitchell Lee Milanuk

Theses & Dissertations

Coronary artery diseases, such as angina or myocardial infarction, are extremely prevalent and impact millions of people worldwide. Underlying the diseases, and how they affect each individual in a distinct manner, is the individual’s coronary artery anatomy. The aim of the present study is to have an intimate knowledge of the normal and variant anatomy of the coronary arteries. As an attempt to gain such knowledge, complete analysis of the anatomical variations of coronary arteries was performed. Classical cadaveric dissection of sixty human hearts was performed in the gross anatomy laboratory at the University of Nebraska Medical Center (UNMC). Precise …

Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure

Theses & Dissertations

Preterm birth is a complex multifactorial process. Despite the well-known role of the placenta in supporting the fetal development and maternal-fetal tolerance, the placental epigenetic modifications and preterm birth (PTB) remains poorly understood and under investigated. Various maternal and environment factors can influence epigenetic programming during fetal development to affect the functioning and structures of organs, including the placenta, which can lead to adverse pregnancy outcomes, including PTB. The understanding of the placental epigenetic alterations and maternal determinants associated with PTB are apparently indispensable for the development of actual diagnosis and methods of prevention and treatment of premature labor. The …

Analysis Of Graded Gross Anatomy Dissections And Demonstrations As A Supplemental Educational Tool, Stephanie Leanne Cummings

Theses & Dissertations

Teaching and assessment modalities for human anatomy curriculums vary between schools. The University of Nebraska Medical Center utilizes an integrated gross anatomy lab curriculum including hands-on dissection, lecture, and 3-D models. The GCBA 909 course, Human Gross Anatomy Lab, just recently incorporated graded dissections and demonstrations into their master of medical anatomy (MMA) curriculum. Students were required to complete and demonstrate eight additional dissections compared to physician assistant (PA), physical therapy (PT) students. Upon completion of these dissections, students were assessed based on the quality of their dissections and were also required to demonstrate the cadaveric dissections to anatomy faculty …

Anatomical Variations Of The Sciatic Nerve Divisions In Relation To The Piriformis Muscle And Clinical Implications, Jonathan I. Van Erdewyk

Theses & Dissertations

The goal of this project was to identify and quantify the anatomical variations of the sciatic nerve divisions in relation to the piriformis muscle and compare the data collected to the primary literature. This was done in an effort to provide awareness of sciatic nerve entrapments within the subgluteal space that may be responsible for posterior hip and buttock pain. While the current means of diagnosis are through physical examination, imaging techniques, and surgery, the results of this present study indicate that new methods of diagnosis need to be explored.

Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson

Journal Articles: Pulmonary & Critical Care Med

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and …