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Full-Text Articles in Medical Specialties

Lipid Droplet Membrane Proteome Remodeling Parallels Ethanol-Induced Hepatic Steatosis And Its Resolution, Carol A. Casey, Terrence Donohue, Jacy L. Kubik, Vikas Kumar, Michael J. Naldrett, Nicholas T. Woods, Cole P. Frisbie, Mark A. Mcniven, Paul G. Thomes Feb 2021

Lipid Droplet Membrane Proteome Remodeling Parallels Ethanol-Induced Hepatic Steatosis And Its Resolution, Carol A. Casey, Terrence Donohue, Jacy L. Kubik, Vikas Kumar, Michael J. Naldrett, Nicholas T. Woods, Cole P. Frisbie, Mark A. Mcniven, Paul G. Thomes

Journal Articles: Internal Medicine

Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either refed …


Echocardiographic Screening Of Anomalous Origin Of Coronary Arteries In Athletes With A Focus On High Take-Off, Massimiliano Cantinotti, Raffaele Giordano, Nadia Assanta, Martin Koestenberger, Eliana Franchi, Pietro Marchese, Alberto Clemente, Shelby Kutty, Flavio D'Ascenzi Feb 2021

Echocardiographic Screening Of Anomalous Origin Of Coronary Arteries In Athletes With A Focus On High Take-Off, Massimiliano Cantinotti, Raffaele Giordano, Nadia Assanta, Martin Koestenberger, Eliana Franchi, Pietro Marchese, Alberto Clemente, Shelby Kutty, Flavio D'Ascenzi

Journal Articles: Pediatrics

Anomalous aortic origin of coronary arteries (AAOCA) represents a rare congenital heart disease. However, this disease is the second most common cause of sudden cardiac death in apparently healthy athletes. The aim of this systematic review is to analyze the feasibility and the detection rate of AAOCA by echocardiography in children and adults. A literature search was performed within the National Library of Medicine using the following keywords: coronary artery origin anomalies and echocardiography; then, the search was redefined by adding the keywords: athletes, children, and high take-off. Nine echocardiographic studies investigating AAOCA and a total of 33,592 children and …


Phenotypes Of Adults With Congenital Heart Disease Around The Globe: A Cluster Analysis, Edward Callus, Silvana Pagliuca, Sara Boveri, Federico Ambrogi, Koen Luyckx, Adrienne H. Kovacs, Silke Apers, Werner Budts, Junko Enomoto, Maayke A. Sluman, Jou-Kou Wang, Jamie L. Jackson, Paul Khairy, Stephen C. Cook, Shanthi Chidambarathanu, Luis Alday, Katrine Eriksen, Mikael Dellborg, Malin Berghammer, Bengt Johansson, Andrew S. Mackie, Samuel Menahem, Maryanne Caruana, Gruschen Veldtman, Alexandra Soufi, Susan M. Fernandes, Kamila White, Shelby Kutty, Philip Moons, Approach-Is Consortium And The International Society For Adult Congenital Heart Disease (Isachd) Feb 2021

Phenotypes Of Adults With Congenital Heart Disease Around The Globe: A Cluster Analysis, Edward Callus, Silvana Pagliuca, Sara Boveri, Federico Ambrogi, Koen Luyckx, Adrienne H. Kovacs, Silke Apers, Werner Budts, Junko Enomoto, Maayke A. Sluman, Jou-Kou Wang, Jamie L. Jackson, Paul Khairy, Stephen C. Cook, Shanthi Chidambarathanu, Luis Alday, Katrine Eriksen, Mikael Dellborg, Malin Berghammer, Bengt Johansson, Andrew S. Mackie, Samuel Menahem, Maryanne Caruana, Gruschen Veldtman, Alexandra Soufi, Susan M. Fernandes, Kamila White, Shelby Kutty, Philip Moons, Approach-Is Consortium And The International Society For Adult Congenital Heart Disease (Isachd)

Journal Articles: Pediatrics

OBJECTIVE: To derive cluster analysis-based groupings for adults with congenital heart disease (ACHD) when it comes to perceived health, psychological functioning, health behaviours and quality of life (QoL).

METHODS: This study was part of a larger worldwide multicentre study called APPROACH-IS; a cross sectional study which recruited 4028 patients (2013-2015) from 15 participating countries. A hierarchical cluster analysis was performed using Ward's method in order to group patients with similar psychological characteristics, which were defined by taking into consideration the scores of the following tests: Sense Of Coherence, Health Behavior Scale (physical exercise score), Hospital Anxiety Depression Scale, Illness Perception …


The Evolution And Future Of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, And Oncolytic Bacteria To The Treatment Of Solid Tumors, Kyle M. Pierce, William R. Miklavcic, Kyle P. Cook, Mikayla Sweitzer Hennen, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks, Jessica E. Pullan, Kaitlin M. Dailey Jan 2021

The Evolution And Future Of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, And Oncolytic Bacteria To The Treatment Of Solid Tumors, Kyle M. Pierce, William R. Miklavcic, Kyle P. Cook, Mikayla Sweitzer Hennen, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks, Jessica E. Pullan, Kaitlin M. Dailey

Journal Articles: Pathology and Microbiology

While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap …


High-Throughput Analysis Of Lung Immune Cells In A Combined Murine Model Of Agriculture Dust-Triggered Airway Inflammation With Rheumatoid Arthritis, Rohit Gaurav, Ted R. Mikuls, Geoffrey M. Thiele, Amy J. Nelson, Meng Niu, Chittibabu Guda, James D. Eudy, Austin E. Barry, Todd A. Wyatt, Debra J. Romberger, Michael J. Duryee, Bryant R. England, Jill A. Poole Jan 2021

High-Throughput Analysis Of Lung Immune Cells In A Combined Murine Model Of Agriculture Dust-Triggered Airway Inflammation With Rheumatoid Arthritis, Rohit Gaurav, Ted R. Mikuls, Geoffrey M. Thiele, Amy J. Nelson, Meng Niu, Chittibabu Guda, James D. Eudy, Austin E. Barry, Todd A. Wyatt, Debra J. Romberger, Michael J. Duryee, Bryant R. England, Jill A. Poole

Journal Articles: Internal Medicine

Rheumatoid arthritis (RA)-associated lung disease is a leading cause of mortality in RA, yet the mechanisms linking lung disease and RA remain unknown. Using an established murine model of RA-associated lung disease combining collagen-induced arthritis (CIA) with organic dust extract (ODE)-induced airway inflammation, differences among lung immune cell populations were analyzed by single cell RNA-sequencing. Additionally, four lung myeloid-derived immune cell populations including macrophages, monocytes/macrophages, monocytes, and neutrophils were isolated by fluorescence cell sorting and gene expression was determined by NanoString analysis. Unsupervised clustering revealed 14 discrete clusters among Sham, CIA, ODE, and CIA+ODE treatment groups: 3 neutrophils (inflammatory, resident/transitional, …


Structure And Activity Of A Selective Antibiofilm Peptide Sk-24 Derived From The Nmr Structure Of Human Cathelicidin Ll-37, Yingxia Zhang, Jayaram Lakshmaiah Narayana, Qianhui Wu, Xiangli Dang, Guangshun Wang Jan 2021

Structure And Activity Of A Selective Antibiofilm Peptide Sk-24 Derived From The Nmr Structure Of Human Cathelicidin Ll-37, Yingxia Zhang, Jayaram Lakshmaiah Narayana, Qianhui Wu, Xiangli Dang, Guangshun Wang

Journal Articles: Pathology and Microbiology

The deployment of the innate immune system in humans is essential to protect us from infection. Human cathelicidin LL-37 is a linear host defense peptide with both antimicrobial and immune modulatory properties. Despite years of studies of numerous peptides, SK-24, corresponding to the long hydrophobic domain (residues 9–32) in the anionic lipid-bound NMR structure of LL-37, has not been investigated. This study reports the structure and activity of SK-24. Interestingly, SK-24 is entirely helical (~100%) in phosphate buffer (PBS), more than LL-37 (84%), GI-20 (75%), and GF-17 (33%), while RI-10 and 17BIPHE2 are essentially randomly coiled (helix%: 7–10%). These results …


Immunopathogenesis Of Craniotomy Infection And Niche-Specific Immune Responses To Biofilm, Sharon D.B. De Morais, Gunjan Kak, Joseph P. Menousek, Tammy Kielian Jan 2021

Immunopathogenesis Of Craniotomy Infection And Niche-Specific Immune Responses To Biofilm, Sharon D.B. De Morais, Gunjan Kak, Joseph P. Menousek, Tammy Kielian

Journal Articles: Pathology and Microbiology

Bacterial infections in the central nervous system (CNS) can be life threatening and often impair neurological function. Biofilm infection is a complication following craniotomy, a neurosurgical procedure that involves the removal and replacement of a skull fragment (bone flap) to access the brain for surgical intervention. The incidence of infection following craniotomy ranges from 1% to 3% with approximately half caused by Staphylococcus aureus (S. aureus). These infections present a significant therapeutic challenge due to the antibiotic tolerance of biofilm and unique immune properties of the CNS. Previous studies have revealed a critical role for innate immune responses …


The Promise Of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are The Data?, Kimberly Scarsi, Susan Swindells Jan 2021

The Promise Of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are The Data?, Kimberly Scarsi, Susan Swindells

Journal Articles: Infectious Diseases

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community …


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 Jan 2021

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 Jan 2021

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 Jan 2021

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 Jan 2021

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 (VD/VT) 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 Jan 2021

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 …


Collagen Fiber Regulation In Human Pediatric Aortic Valve Development And Disease, Cassandra L. Clift, Yan Ru Su, David Bichell, Heather Jensen Smith, Jennifer R. Bethard, Kim Norris-Caneda, Susana Comte-Walters, Lauren E. Ball, Michael A. Hollingsworth, Anand S. Mehta, Richard R. Drake, Peggi M. Angel Jan 2021

Collagen Fiber Regulation In Human Pediatric Aortic Valve Development And Disease, Cassandra L. Clift, Yan Ru Su, David Bichell, Heather Jensen Smith, Jennifer R. Bethard, Kim Norris-Caneda, Susana Comte-Walters, Lauren E. Ball, Michael A. Hollingsworth, Anand S. Mehta, Richard R. Drake, Peggi M. Angel

Journal Articles: Eppley Institute

Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), …


Child Health And The Implementation Of Community And District-Management Empowerment For Scale-Up (Codes) In Uganda: A Randomised Controlled Trial, Peter Waiswa, Flavia Mpanga, Danstan Bagenda, Rornald Muhumuza Kananura, Thomas O'Connell, Dorcus Kiwanuka Henriksson, Theresa Diaz, Florence Ayebare, Anne Ruhweza Katahoire, Eric Ssegujja, Anthony Mbonye, Stefan Swartling Peterson Jan 2021

Child Health And The Implementation Of Community And District-Management Empowerment For Scale-Up (Codes) In Uganda: A Randomised Controlled Trial, Peter Waiswa, Flavia Mpanga, Danstan Bagenda, Rornald Muhumuza Kananura, Thomas O'Connell, Dorcus Kiwanuka Henriksson, Theresa Diaz, Florence Ayebare, Anne Ruhweza Katahoire, Eric Ssegujja, Anthony Mbonye, Stefan Swartling Peterson

Journal Articles: Anesthesiology

INTRODUCTION: Uganda's district-level administrative units buttress the public healthcare system. In many districts, however, local capacity is incommensurate with that required to plan and implement quality health interventions. This study investigates how a district management strategy informed by local data and community dialogue influences health services.

METHODS: A 3-year randomised controlled trial (RCT) comprised of 16 Ugandan districts tested a management approach, Community and District-management Empowerment for Scale-up (CODES). Eight districts were randomly selected for each of the intervention and comparison areas. The approach relies on a customised set of data-driven diagnostic tools to identify and resolve health system bottlenecks. …


A Comprehensive Study To Delineate The Role Of An Extracellular Vesicle-Associated Microrna-29a In Chronic Methamphetamine Use Disorder, Subhash Chand, Austin Gowen, Mason Savine, Dalia Moore, Alexander Clark, Wendy Huynh, Niming Wu, Katherine Odegaard, Lucas Weyrich, Rick A. Bevins, Howard S. Fox, Gurudutt Pendyala, Sowmya V. Yelamanchili Jan 2021

A Comprehensive Study To Delineate The Role Of An Extracellular Vesicle-Associated Microrna-29a In Chronic Methamphetamine Use Disorder, Subhash Chand, Austin Gowen, Mason Savine, Dalia Moore, Alexander Clark, Wendy Huynh, Niming Wu, Katherine Odegaard, Lucas Weyrich, Rick A. Bevins, Howard S. Fox, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non-human primate and rodent model systems, we provide evidence that brain-derived EV (BDE) miRNA, miR-29a-3p (mir-29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR-29a levels show significant increase both with drug-seeking and reinstatement in a rat MA self-administration model. We also show that EV-associated miR-29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA-induced inflammation and synaptodendritic …


A Holistic Systems Approach To Characterize The Impact Of Pre- And Post-Natal Oxycodone Exposure On Neurodevelopment And Behavior, Katherine E. Odegaard, Victoria L. Schaal, Alexander R. Clark, Sneh Koul, Jagadesan Sankarasubramanian, Zhiqiu Xia, Melissa Mellon, Mariano Uberti, Yutong Liu, Andrew Stothert, Matthew J. Van Hook, Han-Jun Wang, Chittibabu Guda, Steven J. Lisco, Gurudutt Pendyala, Sowmya V. Yelamanchili Jan 2021

A Holistic Systems Approach To Characterize The Impact Of Pre- And Post-Natal Oxycodone Exposure On Neurodevelopment And Behavior, Katherine E. Odegaard, Victoria L. Schaal, Alexander R. Clark, Sneh Koul, Jagadesan Sankarasubramanian, Zhiqiu Xia, Melissa Mellon, Mariano Uberti, Yutong Liu, Andrew Stothert, Matthew J. Van Hook, Han-Jun Wang, Chittibabu Guda, Steven J. Lisco, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes. Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (1H-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood. Results: 1 …


Crosstalk Between Staphylococcus Aureus And Innate Immunity: Focus On Immunometabolism, Christopher M. Horn, Tammy Kielian Jan 2021

Crosstalk Between Staphylococcus Aureus And Innate Immunity: Focus On Immunometabolism, Christopher M. Horn, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of bacterial infections globally in both healthcare and community settings. The success of this bacterium is the product of an expansive repertoire of virulence factors in combination with acquired antibiotic resistance and propensity for biofilm formation. S. aureus leverages these factors to adapt to and subvert the host immune response. With the burgeoning field of immunometabolism, it has become clear that the metabolic program of leukocytes dictates their inflammatory status and overall effectiveness in clearing an infection. The metabolic flexibility of S. aureus offers an inherent means by which the pathogen could manipulate the …


Integrated Systems Analysis Of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure, Rahul Guda, Katherine E. Odegaard, Chengxi Tan, Victoria L. Schaal, Sowmya V. Yelamanchili, Gurudutt Pendyala Jan 2021

Integrated Systems Analysis Of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure, Rahul Guda, Katherine E. Odegaard, Chengxi Tan, Victoria L. Schaal, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

Opioid abuse has become a major public health crisis that affects millions of individuals across the globe. This widespread abuse of prescription opioids and dramatic increase in the availability of illicit opioids have created what is known as the opioid epidemic. Pregnant women are a particularly vulnerable group since they are prescribed for opioids such as morphine, buprenorphine, and methadone, all of which have been shown to cross the placenta and potentially impact the developing fetus. Limited information exists regarding the effect of oxycodone (oxy) on synaptic alterations. To fill this knowledge gap, we employed an integrated system approach to …


Alcohol-Induced Lysosomal Damage And Suppression Of Lysosome Biogenesis Contribute To Hepatotoxicity In Hiv-Exposed Liver Cells, Moses New-Aaron, Paul G. Thomes, Murali Ganesan, Raghubendra Singh Dagur, Terrence Donohue, Kusum K. Kharbanda, Larisa Y. Poluektova, Natalia A. Osna Jan 2021

Alcohol-Induced Lysosomal Damage And Suppression Of Lysosome Biogenesis Contribute To Hepatotoxicity In Hiv-Exposed Liver Cells, Moses New-Aaron, Paul G. Thomes, Murali Ganesan, Raghubendra Singh Dagur, Terrence Donohue, Kusum K. Kharbanda, Larisa Y. Poluektova, Natalia A. Osna

Journal Articles: Internal Medicine

Although the causes of hepatotoxicity among alcohol-abusing HIV patients are multifactorial, alcohol remains the least explored “second hit” for HIV-related hepatotoxicity. Here, we investigated whether metabolically derived acetaldehyde impairs lysosomes to enhance HIV-induced hepatotoxicity. We exposed Cytochrome P450 2E1 (CYP2E1)-expressing Huh 7.5 (also known as RLW) cells to an acetaldehyde-generating system (AGS) for 24 h. We then infected (or not) the cells with HIV-1ADA then exposed them again to AGS for another 48 h. Lysosome damage was assessed by galectin 3/LAMP1 co-localization and cathepsin leakage. Expression of lysosome biogenesis–transcription factor, TFEB, was measured by its protein levels and by …


Neural Responses To Fluoxetine In Youths With Disruptive Behavior And Trauma Exposure: A Pilot Study, Soonjo Hwang, Unsun Chung, Yongmin Chang, Eunji Kim, Ji-Woo Suk, Harma Meffert, Christopher J. Kratochvil, Ellen Leibenluft, James Blair Jan 2021

Neural Responses To Fluoxetine In Youths With Disruptive Behavior And Trauma Exposure: A Pilot Study, Soonjo Hwang, Unsun Chung, Yongmin Chang, Eunji Kim, Ji-Woo Suk, Harma Meffert, Christopher J. Kratochvil, Ellen Leibenluft, James Blair

Journal Articles: Psychiatry

Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, …


Early Enteral Feeding In Preterm Infants: A Narrative Review Of The Nutritional, Metabolic, And Developmental Benefits, Melissa K. Thoene, Ann Anderson-Berry Jan 2021

Early Enteral Feeding In Preterm Infants: A Narrative Review Of The Nutritional, Metabolic, And Developmental Benefits, Melissa K. Thoene, Ann Anderson-Berry

Journal Articles: Pediatrics

Enteral feeding is the preferred method of nutrient provision for preterm infants. Though parenteral nutrition remains an alternative to provide critical nutrition after preterm delivery, the literature suggests that enteral feeding still confers significant nutritional and non-nutritional benefits. Therefore, the purpose of this narrative review is to summarize health and clinical benefits of early enteral feeding within the first month of life in preterm infants. Likewise, this review also proposes methods to improve enteral delivery in clinical care, including a proposal for decision-making of initiation and advancement of enteral feeding. An extensive literature review assessed enteral studies in preterm infants …


Intraventricular Septation In The Context Of Dilated Cardiomyopathy Associated With Ttn Mutation, Karl R. Khandalavala, Jean A. Ballweg, Stanley J. Radio, Jeffrey A. Robinson Jan 2021

Intraventricular Septation In The Context Of Dilated Cardiomyopathy Associated With Ttn Mutation, Karl R. Khandalavala, Jean A. Ballweg, Stanley J. Radio, Jeffrey A. Robinson

Journal Articles: Pediatrics

A 6-month-old infant boy presented with symptomatic heart failure. Dilated cardiomyopathy was found in association with a mutation in TTN. Structural heart disease included novel septation of the left ventricle with a fenestrated membrane resulting from aberrant congenital mitral valve apparatus formation. (Level of Difficulty: Advanced.).


A Midwestern Academic Hiv Clinic Operation During The Covid-19 Pandemic: Implementation Strategy And Preliminary Outcomes, Nada Fadul, Nichole Regan, Layan Kaddoura, Susan Swindells Jan 2021

A Midwestern Academic Hiv Clinic Operation During The Covid-19 Pandemic: Implementation Strategy And Preliminary Outcomes, Nada Fadul, Nichole Regan, Layan Kaddoura, Susan Swindells

Journal Articles: Infectious Diseases

During the COVID-19 pandemic, HIV clinics had to transform care delivery for people with HIV (PWH). We developed a multifaceted telehealth implementation strategy and monitored number of out of care patients (OOC), medical visit frequency (MVF), gap in care (GiC) and viral suppression (VS), and compared measures to baseline data. Between April and October 2020, 1559 visits were scheduled; 328 (21%) were missed, and 63 (4%) were new to care. Of the remaining 1168 follow-up visits, 412 (35%) were telehealth visits. As of October 2020, there were 53 patients OOC, MVF was 55% and GiC was 24% compared to 34, …


Intrauterine Transfer Of Polyunsaturated Fatty Acids In Mother–Infant Dyads As Analyzed At Time Of Delivery, Vanessa Woodward, Melissa K. Thoene, Matthew Van Ormer, Maranda Thompson, Corrine K. Hanson, Sathish Kumar Natarajan, Maheswari Mukherjee, Ana G. Yuil-Valdes, Tara M. Nordgren, Arzu Ulu, Kristina Harris Jackson, Ann Anderson-Berry Jan 2021

Intrauterine Transfer Of Polyunsaturated Fatty Acids In Mother–Infant Dyads As Analyzed At Time Of Delivery, Vanessa Woodward, Melissa K. Thoene, Matthew Van Ormer, Maranda Thompson, Corrine K. Hanson, Sathish Kumar Natarajan, Maheswari Mukherjee, Ana G. Yuil-Valdes, Tara M. Nordgren, Arzu Ulu, Kristina Harris Jackson, Ann Anderson-Berry

Journal Articles: Pediatrics

Polyunsaturated fatty acids (PUFAs) are essential for fetal development, and intrauterine transfer is the only supply of PUFAs to the fetus. The prevailing theory of gestational nutrient transfer is that certain nutrients (including PUFAs) may have prioritized transport across the placenta. Numerous studies have identified correlations between maternal and infant fatty acid concentrations; however, little is known about what role maternal PUFA status may play in differential intrauterine nutrient transfer. Twenty mother–infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood, and placental tissue samples. Plasma concentrations of PUFAs were assessed using gas chromatography (GC-FID). Intrauterine …


Qupath Digital Immunohistochemical Analysis Of Placental Tissue, Ashley L. Hein, Maheswari Mukherjee, Geoffrey A. Talmon, Sathish Kumar Natarajan, Tara M. Nordgren, Elizabeth Lyden, Corrine K. Hanson, Jesse L. Cox, Annelisse Santiago-Pintado, Mariam A. Molani, Matthew Van Ormer, Maranda Thompson, Melissa K. Thoene, Aunum Akhter, Ann Anderson-Berry, Ana G. Yuil-Valdes Jan 2021

Qupath Digital Immunohistochemical Analysis Of Placental Tissue, Ashley L. Hein, Maheswari Mukherjee, Geoffrey A. Talmon, Sathish Kumar Natarajan, Tara M. Nordgren, Elizabeth Lyden, Corrine K. Hanson, Jesse L. Cox, Annelisse Santiago-Pintado, Mariam A. Molani, Matthew Van Ormer, Maranda Thompson, Melissa K. Thoene, Aunum Akhter, Ann Anderson-Berry, Ana G. Yuil-Valdes

Journal Articles: Pediatrics

Background: QuPath is an open-source digital image analyzer notable for its user-friendly design, cross-platform compatibility, and customizable functionality. Since it was first released in 2016, at least 624 publications have reported its use, and it has been applied in a wide spectrum of settings. However, there are currently limited reports of its use in placental tissue. Here, we present the use of QuPath to quantify staining of G-protein coupled receptor 18 (GPR18), the receptor for the pro-resolving lipid mediator Resolvin D2, in placental tissue.

Methods: Whole slide images of vascular smooth muscle (VSM) and extravillous trophoblast (EVT) cells stained for …


Pandemic Driven Innovation: Development Of An Alternative Respiratory Pathogen Self-Collection Device, Thang Nguyen Dec 2020

Pandemic Driven Innovation: Development Of An Alternative Respiratory Pathogen Self-Collection Device, Thang Nguyen

Theses & Dissertations

The SARS-CoV-2 virus outbreak has underscored numerous weak links in our biodefense countermeasures against highly communicable diseases. Many believe it was our lack of an effective testing model that allowed the virus to become a global pandemic within a short period. The gold standard collection method for the SARS-CoV-2 virus involves mechanical debridement of the nasopharyngeal cavity with a stiff swab applicator, which has been known to cause pain and injury to patients, subsequently resulting in low patient acceptance of the procedure. Due to the invasive nature of the nasopharyngeal swab collection method, it may not be conducive to the …


Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo Dec 2020

Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo

Theses & Dissertations

Patients with cancer experience metabolic changes such as hypoglycemia, hyperglycemia, and glycemic variability; collectively termed malglycemia. Glycemic variability, defined as fluctuations in glucose, is a marker of metabolic instability. Higher glycemic variability is associated with adverse health outcomes in the general population and in those with diabetes. Little is known about glycemic variability in patients with cancer, especially those with solid tumor malignancies. Glycemic variability is associated with increased infection, shorter periods of remission, and higher mortality in patients with hematological cancer. This body of work describes the concept and measurement of glycemic variability to assess glycemic control in patients …


Spare Parts Surgery For Oncologic Reconstruction To Preserve Local Advancement Flap For Decubitus Ulcer Reconstruction: A Case Report, Emily Zurbuchen, Nathan Foje, Sean Figy Dec 2020

Spare Parts Surgery For Oncologic Reconstruction To Preserve Local Advancement Flap For Decubitus Ulcer Reconstruction: A Case Report, Emily Zurbuchen, Nathan Foje, Sean Figy

Graduate Medical Education Research Journal

A 58-year-old male presented to our institution with synchronous large left thigh sarcoma and sacral decubitus ulcer requiring oncologic resection and reconstruction. Due to extensive tumor involvement, use of local flap for reconstruction was not feasible. Therefore, a spare parts free fillet flap from the disarticulated lower leg was utilized for reconstruction following oncologic resection. The benefits of this spare parts approach include no donor site morbidity, sufficient tissue padding for later use of prosthesis, and preservation of other flaps for future reconstruction of his sacral decubitus ulcer.


Multi-Digit Auto-Amputation In Setting Of Mixed Connective Tissue Disease, Kishan P. Patel, Jennifer L. Medlin, Michelene Hearth-Holmes Dec 2020

Multi-Digit Auto-Amputation In Setting Of Mixed Connective Tissue Disease, Kishan P. Patel, Jennifer L. Medlin, Michelene Hearth-Holmes

Graduate Medical Education Research Journal

Raynaud’s disease is a cutaneous manifestation often present in various connective tissue and vascular diseases. Depending on the age of onset and acuity of symptoms, the phenomenon can provide clinicians with some insight as to the severity of underlying disease, including the distinction between primary and secondary Raynaud’s. However, this diagnostic approach seems to have its limitations regarding efficacy and timing of treatment. Traditionally, treatment of Raynaud’s has focused on reestablishing blood perfusion to affected tissue, which has previously been achieved with vasodilatory medications and site-specific surgical intervention. In lieu of the severe sequelae of Raynaud’s in the setting of …