Anatomy Commons^™

Z Variant Heterozygosity In Alpha-1 Antitrypsin Deficiency: Disease Risk And Treatment Implications, Craig P. Hersh, Jeffrey H. Teckman, Pavel Strnad, Aaron Hakim, Tomás P. Carroll, Ian P. Hall, Auyon J. Ghosh, Igor Barjaktarevic, Noel G. Mcelvaney, Joseph E. Kaserman, David A. Lomas, Charlie Strange, M Bradley Drummond, Stephen I. Rennard, Kathi E. Hanna, Virginia C. Clark, Monica P. Goldklang, Peg Iverson, Andrew A. Wilson

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Individuals heterozygous for alpha-1 antitrypsin deficiency (AATD) have one copy of the normal "M" allele and one copy of an abnormal allele ("Z", "S", or another variant) in the SERPINA1 gene. Historically, evidence has been lacking to support the concept that heterozygotes are at increased risk for liver and/or lung complications compared to individuals homozygous for the M allele. However, growing evidence suggests that inheritance of a single Z allele increases the risk of disease in some individuals. The Alpha-1 Foundation convened a workshop on October 27, 2023, in Bethesda, Maryland that included stakeholders from the research, pharmaceutical, and …

Bayesian Reanalysis Of Early Remdesivir For The Treatment Of Covid-19 In Outpatients With High Risk Of Progression To Severe Disease, Mazin Abdelghany, Fang Yu, Stephen I. Rennard, Yeongjin Gwon

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Though Bayesian methods are flexible, intuitive, and readily incorporated into clinical decision-making, with particular utility when prior information is available, they remain underutilized in the analysis of clinical trials.

METHODS: In PINETREE, a Phase 3 randomized controlled trial (RCT) of remdesivir (RDV) for the treatment of outpatients with COVID-19 at high risk of severe disease, the primary outcome of COVID-19-related hospitalization or all-cause death was reanalyzed using a range of reference and data-driven priors. Posterior probability distributions were used to calculate the probability that the estimated hazard ratio (HR) was below a range of clinically meaningful specified thresholds and …

Intersections Of Art And Medicine, Lina Adwer

EMET Projects

No abstract provided.

Evaluation Of The Usage And Effectiveness Of The Gross Anatomy Osteology E-Learning Module, Conor Young

Theses & Dissertations

Supplementary online learning modalities have reached near ubiquity in graduate health sciences education, yet evidence about their effectiveness remains mixed. The Department of Genetics, Cell Biology, and Anatomy at UNMC recently introduced their own bespoke electronic study platform called the Osteology e-Learning Module to aid gross anatomy students in the study of osteology. To assess its effectiveness, osteology and whole gross lab practical exam scores were compared in four different content units across three school year cohorts of graduate students in the same gross anatomy class. A survey was also distributed to one cohort to capture subjective information about the …

Electronic And Regular Cigarettes Induce Transcriptional And Physiological Changes In Cardiomyocytes, Hesham Basma, Kajari Dhar, Jason Payne, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cigarette smoking is an important etiology for cardiac diseases and electronic cigarettes are increasing in popularity. In the current study, we assessed physiological and transcriptional changes in human induced pluripotent stem cell derived cardiomyocytes (iPS-CMs) after exposure to electronic cigarette extract (ECE) and conventional cigarette extract (CSE).

METHODS: iPS-CMS were plated on multi-electrode array plates (MEA), electrical and contractile properties were determined by Maestro Edge and computer assisted video analysis (MuscleMotion). Transcriptional profiles were accessed by direct digital mRNA detection of heart failure targeted genes.

RESULTS: Both ECE and CSE extracts significantly prolong beat period from baseline compared to …

Zinc Promotes Mitochondrial Health Through Pgc-1alpha Enhancing Bacterial Clearance In Macrophages Infected With Mycobacterium Avium Complex, Ruxana Sadikot, Prabagaran Narayanasamy, Zhihong Yuan, Deandra R. Smith, Daren L. Knoell

Journal Articles: Pulmonary & Critical Care Med

Mitochondria are increasingly recognized as important contributors to immune function, in addition to energy production. They exert this influence through modulation of various signaling pathways that regulate cellular metabolism and immune function in response to pathogens. Peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha (PGC-1α) is the primary transcription factor and regulator involved in mitochondrial biogenesis. Long known to be involved in immune function, zinc (Zn) is also required for proper mitochondrial function. It is increasingly recognized that many cellular immunometabolic activities are also Zn-dependent. Taken together, we investigated the role of Zn deficiency, both dietary and genetically induced, and Zn …

Gallium Β-Cyclodextrin Nanoparticles Containing Both Gallium Protoporphyrin And Gallium Nitrate Exhibit Antimicrobial Activity Against Nontuberculous Mycobacteria In Vitro And In Vivo, Seoung-Ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pulmonary & Critical Care Med

Effective and safe antibiotics active against pathogenic mycobacterial species are needed. Iron is an essential element for bacterial survival. Ga(NO₃)₃ (GN) and Ga protoporphyrin (GP) as iron mimetics have each been shown to inhibit the iron metabolism and growth of various mycobacterial species. In this study, the dual cyclodextrin nanoparticle (CDGPGN) is prepared that carries GP and GN using a sonication homogenization technique to increase the efficacy of the combination therapy. CDGPGN shows a long-acting antimicrobial activity against Mycobacteroides abscessus residing in monocyte-derived macrophages (MDM). A murine pulmonary study showed that the CDGPGN also inhibited the growth …

Editing Approaches To Treat Alpha-1 Antitrypsin Deficiency, Derek M. Erion, Leah Y. Liu, Christopher R. Brown, Stephen I. Rennard, Humam Farah

Journal Articles: Pulmonary & Critical Care Med

TOPIC IMPORTANCE: Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder most commonly due to a single G to A point mutation (E342K), leading to debilitating lung and/or liver disorders and is associated with increased mortality. The E342K point mutation causes a conformational change of the AAT protein resulting in its retention in liver hepatocytes. This reduces AAT secretion into the serum resulting in higher protease activities due to the lack of inhibition from AAT, causing damage to healthy lung tissue. The current standard of care for lung manifestations involves weekly IV augmentation therapy and is considered suboptimal for these patients. …

Patient-Centered Preimplant Education Session And Bi-Weekly Text Message Adherence Reminders In Patients With A Newly Implanted Cardiomems® Device: A Quality Improvement Study, Elizabeth M. Miller, Alicia Abboud, Audrey Cooper

Doctor of Nursing Practice Projects: College of Nursing

Rationale

Heart failure is a deadly disease, affecting over 6.2 million individuals and costing the United States an estimated 30.7 billion dollars (Virani et al., 2020). By 2023, heart failure costs in the United States are estimated to grow to 70 billion dollars with 75-80% of these costs attributed to inpatient hospitalizations (Heidereich et al., 2022). The CardioMEMs® is a small device placed in the patient’s pulmonary artery via a minimally invasive procedure by an interventional cardiologist. The use of remote patient data from the CardioMEMs® device has been shown to reduce hospital re-admissions, facilitate tailored medication management, detect increased …

Sensory Dysfunction And The Role Of Nrf2 In The Production Of Pain In Chronic Hindlimb Ischemia, Oliver Kitzerow

Theses & Dissertations

Peripheral arterial disease (PAD) is a progressive and debilitating atherothrombotic disorder that is estimated to impact >200 million people worldwide. Higher physical activity levels are associated with better overall survival rates, slower decline of functional capability, and improved quality of life. However, intermittent claudication, pain produced by physical activity, severely limits functional capacity in PAD patients. Despite known sensory dysfunction and documented neuropathy in diseased patients, the neural mechanisms that produce pain in PAD are yet to be identified. Importantly, few animal models of hindlimb ischemia (HLI) successfully recapitulate chronic human PAD. We developed a chronic animal model of HLI …

Normal And Varied Morphological Structure Of The Fossa Ovalis And Its Clinical Relevance, Christian G. Valverde

Theses & Dissertations

Congenital heart defects are atop the list of the most common type of birth defects in modern obstetrics. According to the Center for Disease Control and Prevention, nearly 40,000 births each year are diagnosed with a congenital heart defect, composing an annual rate of 1%. Of those 40,000 births, roughly 1 in 4 are severe enough to require surgical intervention. Acknowledging that heart disease has been the leading cause of mortality for the past several decades, the former can certainly have additive effects toward this trend. There are several different etiologies and forms of heart defects that are often found …

Targeting Transitioning Lung Monocytes/Macrophages As Treatment Strategies In Lung Disease Related To Environmental Exposures, Aaron Schwab, Todd A. Wyatt, Grace Moravec, Geoffrey M. Thiele, Amy J. Nelson, Angela Gleason, Oliver Schanze, Michael J. Duryee, Debra J. Romberger, Ted R. Mikuls, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Background: Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited,transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear.

Methods: CCR2 RFP⁺ mice were intratracheally instilled with high concentration ODE (25%), LPS (10 μg), or gram-positive peptidoglycan (PGN, 100 μg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure.Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. …

Lung-Delivered Il-10 Therapy Elicits Beneficial Effects Via Immune Modulation In Organic Dust Exposure-Induced Lung Inflammation, Aaron D. Schwab, Todd A. Wyatt, Amy J. Nelson, Angela Gleason, Rohit Gaurav, Debra J. Romberger, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Efficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 μg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 …

Polygenic And Transcriptional Risk Scores Identify Chronic Obstructive Pulmonary Disease Subtypes In The Copdgene And Eclipse Cohort Studies, Matthew Moll, Julian Hecker, John Platig, Jingzhou Zhang, Auyon J. Ghosh, Katherine A. Pratte, Rui-Sheng Wang, Davin Hill, Iain R. Konigsberg, Joe W. Chiles, Craig P. Hersh, Peter J. Castaldi, Kimberly Glass, Jennifer G. Dy, Don D. Sin, Ruth Tal-Singer, Majd Mouded, Stephen I. Rennard, Gary P. Anderson, Gregory L. Kinney, Russell P. Bowler, Jeffrey L. Curtis, Merry-Lynn Mcdonald, Edwin K. Silverman, Brian D. Hobbs, Michael H. Cho

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

METHODS: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing …

Massive Upper Gi Bleeding From Duodenal Invasion Of Hepatocellular Carcinoma Successfully Treated With Embolization And Hemospray®, Patrick Twohig, Erin Walsh, Amy Calderon

Graduate Medical Education Research Journal

Direct invasion of hepatocellular carcinoma (HCC) into the duodenum is a unique and life-threatening complication of HCC that has been rarely reported. A 60-year-old male with known HCC and cirrhosis presented with melena. Computed tomography of the abdomen and pelvis showed a 7cm hepatic mass abutting the duodenum. Esophagogastroduodenoscopy demonstrated a large, actively oozing mass in the duodenum treated with Hemospray® followed by transarterial embolization (TAE). Active upper gastrointestinal bleeding due to duodenal invasion of HCC can be successfully treated with Hemospray® Endoscopic Hemostat and TAE.

Prostatic Utricle Presenting As A Midline Scrotal Mass, Kaitlyn E. Schultis, Bryant Van Leeuwen, John Makari

Graduate Medical Education Research Journal

The prostatic utricle is a remnant of the Müllerian duct located within the verumontanum. An enlarged, clinically significant prostatic utricle has classically been associated with hypospadias. Prostatic utricles often present with persistent lower urinary tract symptoms, recurrent infections, and urinary incontinence. We present a prostatic utricle that presented as a scrotal mass concerning for rhabdomyosarcoma in a male with normal external genitalia.

Botulinum Toxin Type A Injections For Refractory Abdominal Dystonia: A Case Report, William J. Naber Ii, Jodi M. Wilhelm, Kurt A. Kuhlman, Gabriel Howard

Graduate Medical Education Research Journal

Background: A 58-year-old male with chronic bilateral treatment resistant abdominal spasms secondary complications of ascites/ alcoholic cirrhosis. Spasms would occur 4-5 times/day, lasting minutes to hours despite a 2-year course of therapeutic and pharmacological interventions. Due to treatment refraction, 6 uniformly spaced botulinum toxin type A (BTX-A) injections were placed per side, using electromyography for audible intramuscular syringe placement confirmation, while visual confirmation was made via ultrasound. During the initial trial, 6 evenly spaced injections were performed bilaterally, uniformly distributing 80U/side. Injections began bilaterally just medial to the junction of the inferior rib cage border/ anterior axillary line and progressed …

Stellate Ganglion Block For Refractory Raynaud’S Phenomenon- A Case Report, William J. Naber Ii, Derik J. Scribner, Gabriel Howard

Graduate Medical Education Research Journal

Introduction: Raynaud’s phenomenon (RP) is predominately a sympathetically mediated ischemic vasospastic disease involving the distal limbs and is associated with sharp pains, numbness, and dermatological color changes. The symptoms are commonly induced by cold weather, stress, and trauma and it is known to affect 4.85% of the population. There are few well-defined treatments for patients with RP that are refractory to 1st-line therapies. We present a case of intractable RP with corresponding response to stellate ganglion block (SGB) which demonstrates the efficacy profile and safety of SNS blocks in treatment of resistant RP.

Methods: Per Bon Secours Mercy Health …

Preparing For The Unexpected: Recognizing A Tortuous Thoracic Aorta During Ultrasound-Guided Thoracentesis, Michael Choi, Jessica Roettger, Christopher J. Smith

Graduate Medical Education Research Journal

Ultrasound-guidance has become the standard of care for bedside thoracentesis. This manuscript describes the importance of utilizing point-of-care-ultrasound (POCUS) and color Doppler in avoiding an unusual, but potentially catastrophic aortic puncture during thoracentesis. The case describes a 70 year-old man who presented with one week of shortness of breath. He was found to have a large left-sided pleural effusion on imaging studies. During a bedside POCUS examination, he was found to have a hyperechoic linear structure in his posterior left hemithorax. Ultrasound application of color Doppler revealed a pulsatile flow, confirming visualization of the aorta. The site of needle insertion …

Cystic Duct Morphology And Heister Valves: A Cadaveric Study, Cierra R. Goerish

Theses & Dissertations

Continued occurrence of cholelithiasis, gallstones, commonly results in cholecystectomy, removal of the gallbladder. Having a comprehensive anatomical, histological, and physiological knowledge of the biliary apparatus is imperative in clinical medicine today. Additionally, the functionality of cystic duct (CD) Heister valves (HV) has been speculatory since being reported in 1732. This study summarizes the morphology, orientation, and variability of the gross biliary system and provides data to help justify HV functionality.

Cadaveric dissection was utilized for gross observation and analysis of the biliary system. The angulation of the CD was found primarily as an acute angle; however, obtuse angulation could be …

Variations In Source And Pattern Of Arterial Supply To The Trigeminal Ganglion With Clinical Relevance, William S. Srinivasan

Theses & Dissertations

The trigeminal ganglion (TG) is known to receive its arterial supply from branches of the internal carotid artery (ICA), middle meningeal artery (MMA), accessory meningeal artery (AMA), or superior cerebellar artery (SCA). Existing information about the prevalence and patterns of blood supply to the TG is limited despite their high clinical relevance to basicranial surgeries. The objective of this study is to investigate the source and pattern of arterial supply to TG and discuss their clinical relevance. Left and right TG were examined on 75 embalmed human cadavers from an ethically approved anatomical donor program. A literature review was conducted, …

Agricultural Dust Derived Bacterial Extracellular Vesicle Mediated Inflammation Is Attenuated By Dha, Art J. Heires, Derrick R. Samuelson, Daniel Villageliu, Tara M. Nordgren, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Dietary long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and their pro-resolving metabolites are protective against atherosclerotic disease, and ameliorate systemic inflammatory conditions including lupus erythematosus, psoriasis, and bronchial asthma. Organic bioaerosol inhalation is a common and injurious hazard associated with agricultural occupations such as work in swine concentrated animal feeding operations (CAFOs) and is known to increase the risk for developing respiratory conditions such as asthma and COPD. Nearly all cells secrete membrane-bound vesicles (extracellular vesicles, EVs) that have the capacity to transmit protein, nucleic acid, and lipid signaling mediators between cells. Using a polymer-based isolation technique (ExoQuick, PEG) followed …

Icenticaftor, Novel Therapy For Copd: This Glass Is Half Full, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

No abstract provided.

Longitudinal Assessment Of Multimorbidity Medication Patterns Among Smokers In The Copdgene Cohort, Yisha Li, Sarah J. Schmiege, Heather Anderson, Nicole E. Richmond, Kendra A. Young, John E. Hokanson, Stephen I. Rennard, Tessa L. Crume, Erin Austin, Katherine A. Pratte, Rebecca Conway, Gregory L. Kinney

Journal Articles: Pulmonary & Critical Care Med

Background and objectives: Chronic obstructive pulmonary disease (COPD) is usually comorbid with other chronic diseases. We aimed to assess the multimorbidity medication patterns and explore if the patterns are similar for phase 1 (P1) and 5-year follow-up phase 2 (P2) in the COPDGene cohort. Materials and Methods: A total of 5564 out of 10,198 smokers from the COPDGene cohort who completed 2 visits, P1 and P2 visits, with complete medication use history were included in the study. We conducted latent class analysis (LCA) among the 27 categories of chronic disease medications, excluding COPD treatments and cancer medications at P1 and …

Fortuitous Diagnosis Of Total Anomalous Pulmonary Venous Return In A Newborn With Hypoglycemia, Joseph Maes, Terence Zach

Child Health Research Institute Pediatric Research Forum

No abstract provided.

Effective Emodule Design For First-Year Medical Student Anatomy Curricula, Taylor J. Kratochvil Ms, Kaeli K. Samson Ma, Mph, Kari L. Nelson Phd, Travis L. Mccumber Phd

EMET Projects

Introduction: It is critical to evaluate student experience with any newly integrated educational resource. In 2018, a Distal Upper Limb (DUL) Anatomy eModule was developed for first-year medical students at the University of Nebraska Medical Center, who have historically identified the DUL as a region of difficulty. This mixed methods study sought to (1) evaluate learner perception of the eModule relative to other resources, and (2) identify eModule content and features that students found valuable.

Methods: The DUL eModule was made available to first-year medical students in 2019 (n= 132), 2020 (n=131), and 2021 (n=131) as a voluntary, …

Relationships Of Serum Cc16 Levels With Smoking Status And Lung Function In Copd, Kelli C. Gribben, Jill A. Poole, Amy J. Nelson, Paraskevi A. Farazi, Christopher S. Wichman, Art J. Heires, Debra J. Romberger, Tricia D. Levan

Journal Articles: Pulmonary & Critical Care Med

Background: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown.

Methods: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV₁/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation.

Results: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on …

Identifying Individual Medications Affecting Pulmonary Outcomes When Multiple Medications Are Present, Yisha Li, Ran Dai, Yeongjin Gwon, Stephen I. Rennard, Barry J. Make, Dinah Foer, Matthew J. Strand, Erin Austin, Kendra A. Young, John E. Hokanson, Katherine A. Pratte, Rebecca Conway, Gregory L. Kinney, Copdgene Investigators

Journal Articles: Pulmonary & Critical Care Med

No abstract provided.

Updated Perspectives On The Role Of Biomechanics In Copd: Considerations For The Clinician, Jennifer M. Yentes, Wai-Yan Liu, Kuan Zhang, Eric Markvicka, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Patients with chronic obstructive pulmonary disease (COPD) demonstrate extra-pulmonary functional decline such as an increased prevalence of falls. Biomechanics offers insight into functional decline by examining mechanics of abnormal movement patterns. This review discusses biomechanics of functional outcomes, muscle mechanics, and breathing mechanics in patients with COPD as well as future directions and clinical perspectives. Patients with COPD demonstrate changes in their postural sway during quiet standing compared to controls, and these deficits are exacerbated when sensory information (eg, eyes closed) is manipulated. If standing balance is disrupted with a perturbation, patients with COPD are slower to return to baseline …

Endotracheal Tube Dislodgment In A High Risk Pulmonary Hypertensive Patient Due To Undiagnosed Tracheomegaly: A Case Report, Andrew Peck, Tammer N. Ghaly, Austin J. Adams, Daniel W. Johnson, Rebecca A. Aron

Graduate Medical Education Research Journal

Introduction

Airway enlargement was first described histologically in 1872, but it was not clinically reported until 1932, when Dr. Mounier-Kuhn published his seminal radiographic studies.¹ Since then, it is estimated that several hundred case reports have been published on congenital Mounier-Kuhn Syndrome (MKS), acquired tracheomegaly, and tracheobronchomegaly (TBM), yet only a few comprehensive literature reviews exist.²

Case

This case report details an elective nasal procedure for a patient with a history of significant pulmonary hypertension ad COPD on 5L home O₂ who had a symptomatic facial trauma. He was considered high risk secondary to his pulmonary disease, …