Digital Commons Network^™

Leveraging Murine Models Of The Neurofibromatosis Type 1 Cancer Predisposition Syndrome To Elucidate The Cellular Circuits That Drive Pediatric Low-Grade Glioma Formation And Progression, David H Gutmann

2020-Current year OA Pubs

Brain tumors are the leading cause of cancer-related death in children, where low-grade gliomas (LGGs) predominate. One common hereditary cause for LGGs involves neurofibromatosis-1 (NF1) gene mutation, as seen in individuals with the NF1 cancer predisposition syndrome. As such, children with NF1 are at increased risk of developing LGGs of the optic pathway, brainstem, cerebellum, and midline brain structures. Using genetically engineered mouse models, studies have revealed both cell-intrinsic (MEK signaling) and stromal dependencies that underlie their formation and growth. Importantly, these dependencies represent vulnerabilities against which targeted agents can be used for preclinical investigation prior to clinical translation.

Neurosteroids Mediate And Modulate The Effects Of Pro-Inflammatory Stimulation And Toll-Like Receptors On Hippocampal Plasticity And Learning, Yukitoshi Izumi, Kazuko A. O'Dell, Anil G. Cashikar, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski

2020-Current year OA Pubs

Pro-inflammatory changes contribute to multiple neuropsychiatric illnesses. Understanding how these changes are involved in illnesses and identifying strategies to alter inflammatory responses offer paths to potentially novel treatments. We previously found that acute pro-inflammatory stimulation with high (μg/ml) lipopolysaccharide (LPS) for 10-15 min dampens long-term potentiation (LTP) in the hippocampus and impairs learning. Effects of LPS involved non-canonical inflammasome signaling but were independent of toll-like receptor 4 (TLR4), a known LPS receptor. Low (ng/ml) LPS also inhibits LTP when administered for 2-4 h, and here we report that this LPS exposure requires TLR4. We also found that effects of low …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Deanna M. Barch, Andrew C. Heath, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Control Of Acute Myeloid Leukemia And Generation Of Immune Memory In Vivo Using Amv564, A Bivalent Bispecific Cd33 X Cd3 T Cell Engager, Linda G. Eissenberg, Julie K. Ritchey, Michael P. Rettig, Dilan A. Patel, Kiran Vij, Feng Gao, Victoria Smith, Tae H Han, John F. Dipersio

2020-Current year OA Pubs

Off-the-shelf immunotherapeutics that suppress tumor growth and provide durable protection against relapse could enhance cancer treatment. We report preclinical studies on a CD33 x CD3 bivalent bispecific diabody, AMV564, that not only suppresses tumor growth, but also facilitates memory responses in a mouse model of acute myelogenous leukemia (AML). Mechanistically, a single 5-day treatment with AMV564 seems to reduce tumor burden by redirection of T cells, providing a time window for allogeneic or other T cells that innately recognize tumor antigens to become activated and proliferate. When the concentration of bispecific becomes negligible, the effector: target ratio has also shifted, …

Intermuscular Coherence As An Early Biomarker For Amyotrophic Lateral Sclerosis: The Protocol For A Prospective, Multicenter Study, Naoum P Issa, Serdar Aydin, Eric Polley, Nathan Carberry, Mark A. Garret, Sean Smith, Ali A. Habib, Nicholas W. Baumgartner, Betty Soliven, Kourosh Rezania

2020-Current year OA Pubs

OBJECTIVE: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

METHODS: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines. The following subjects will be tested: 1) neurotypical controls; 2) patients with symptomatology suggestive for early ALS but not meeting probable or definite ALS by Awaji Criteria; 3) patients with a known ALS mimic. …

Adherence To Practice Parameters In Medicare Beneficiaries With Amyotrophic Lateral Sclerosis, Osvaldo J. Laurido-Soto, Irene M. Faust, Susan Searles Nielsen, Brad A. Racette

2020-Current year OA Pubs

OBJECTIVE: Physician adherence to evidence-based clinical practice parameters impacts outcomes of amyotrophic lateral sclerosis (ALS) patients. We sought to investigate compliance with the 2009 practice parameters for treatment of ALS patients in the United States, and sociodemographic and provider characteristics associated with adherence.

METHODS: In this population-based, retrospective cohort study of incident ALS patients in 2009-2014, we included all Medicare beneficiaries age ≥20 with ≥1 International Classification of Diseases, Ninth Revision, Clinical Modification ALS code (335.20) in 2009 and no prior years (N = 8,575). Variables of interest included race/ethnicity, sex, age, urban residence, Area Deprivation Index (ADI), and provider …

Thirty-Day Hospital Readmission In Females With Acute Heart Failure And Breast Cancer: A Retrospective Cohort Study From National Readmission Database, Soumya Kambalapalli, Nischit Baral, Timir K. Paul, Prakash Upreti, Fahimeh Talaei, Sarah Ayad, Mahmoud Ibrahim, Vikas Aggarwal, Gautam Kumar, Chadi Alraies, Joshua Mitchell

2020-Current year OA Pubs

BACKGROUND: Breast Cancer and cardiovascular diseases are amongst the two leading causes of mortality in the United States, and the two conditions are connected in part because of recognized cardiotoxicity of cancer treatments. The aim of this study is to investigate the predictors risk factors for thirty-day readmission in female breast cancer survivors presenting with acute heart failure.

METHODS: This is a retrospective cohort study of acute heart failure (AHF) hospitalization in female patients with breast cancer in 2019 using the National Readmission Database (NRD), which is the largest publicly available all-payer inpatient readmission database in the United States. Our …

Stat1 Employs Myeloid Cell-Extrinsic Mechanisms To Regulate The Neutrophil Response And Provide Protection Against Invasive Klebsiella Pneumoniae Lung Infection, Shekina Gonzalez-Ferrer, Zeyu Xiong, Atish Gheware, Janet S Lee, Et Al.

2020-Current year OA Pubs

Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread …

Cep120 Is Essential For Kidney Stromal Progenitor Cell Growth And Differentiation, Ewa Langner, Tao Cheng, Eirini Kefaloyianni, Charles Gluck, Baolin Wang, Moe R Mahjoub

2020-Current year OA Pubs

Mutations in genes that disrupt centrosome structure or function can cause congenital kidney developmental defects and lead to fibrocystic pathologies. Yet, it is unclear how defective centrosome biogenesis impacts renal progenitor cell physiology. Here, we examined the consequences of impaired centrosome duplication on kidney stromal progenitor cell growth, differentiation, and fate. Conditional deletion of the ciliopathy gene Cep120, which is essential for centrosome duplication, in the stromal mesenchyme resulted in reduced abundance of interstitial lineages including pericytes, fibroblasts and mesangial cells. These phenotypes were caused by a combination of delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, …

Non-Invasive Auricular Vagus Nerve Stimulation For Subarachnoid Hemorrhage (Navsah): Protocol For A Prospective, Triple-Blinded, Randomized Controlled Trial, Anna Huguenard, Gansheng Tan, Gabrielle Johnson, Markus Adamek, Andrew Coxon, Terrance Kummer, Joshua Osbun, Ananth Vellimana, David Limbrick, Gregory Zipfel, Peter Brunner, Eric Leuthardt

2020-Current year OA Pubs

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive …

Disruption Of The Nascent Polypeptide-Associated Complex Leads To Reduced Polyglutamine Aggregation And Toxicity, Leeran B. Dublin-Ryan, Ankan K. Bhadra, Heather L. True

2020-Current year OA Pubs

The nascent polypeptide-associate complex (NAC) is a heterodimeric chaperone complex that binds near the ribosome exit tunnel and is the first point of chaperone contact for newly synthesized proteins. Deletion of the NAC induces embryonic lethality in many multi-cellular organisms. Previous work has shown that the deletion of the NAC rescues cells from prion-induced cytotoxicity. This counterintuitive result led us to hypothesize that NAC disruption would improve viability in cells expressing human misfolding proteins. Here, we show that NAC disruption improves viability in cells expressing expanded polyglutamine and also leads to delayed and reduced aggregation of expanded polyglutamine and changes …

Characterization And Individual-Level Prediction Of Cognitive State In The First Year After 'Mild' Stroke, Juan Pablo Saa, Tamara Tse, Gerald Choon-Huat Koh, Philip Yap, Carolyn M. Baum, David E. Uribe-Rivera, Saras M. Windecker, Henry Ma, Stephen M. Davis, Geoffrey A. Donnan, Leeanne M. Carey

2020-Current year OA Pubs

BACKGROUND: Mild stroke affects more than half the stroke population, yet there is limited evidence characterizing cognition over time in this population, especially with predictive approaches applicable at the individual-level. We aimed to identify patterns of recovery and the best combination of demographic, clinical, and lifestyle factors predicting individual-level cognitive state at 3- and 12-months after mild stroke.

METHODS: In this prospective cohort study, the Montreal Cognitive Assessment (MoCA) was administered at 3-7 days, 3- and 12-months post-stroke. Raw changes in MoCA and impairment rates (defined as MoCA<24 points) were compared between assessment time-points. Trajectory clusters were identified using variations of ≥1 point in MoCA scores. To further compare clusters, additional assessments administered at 3- and 12-months were included. Gamma and Quantile mixed-effects regression were used to predict individual MoCA scores over time, using baseline clinical and demographic variables. Model predictions were fitted for each stroke survivor and evaluated using model cross-validation to identify the overall best predictors of cognitive recovery.

RESULTS: Participants' (n = 119) MoCA scores improved from baseline to 3-months …

Trauma Patients Have Reduced Ex Vivo Flow-Dependent Platelet Hemostatic Capacity In A Microfluidic Model Of Vessel Injury, Kimberly A. Thomas, Rassam M. G. Rassam, Ronit Kar, Devin M. Dishong, Katelin C. Rahn, Ricardo Fonseca, Melissa Canas, Jose Aldana, Hussain Afzal, Kelly Bochicchio, Matthew D. Neal, Grant V. Bochicchio, Philip C. Spinella, Susan M. Shea

2020-Current year OA Pubs

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from …

Neurosteroids: Mechanistic Considerations And Clinical Prospects, Jamie L Maguire, Steven Mennerick

2020-Current year OA Pubs

Like other classes of treatments described in this issue's section, neuroactive steroids have been studied for decades but have risen as a new class of rapid-acting, durable antidepressants with a distinct mechanism of action from previous antidepressant treatments and from other compounds covered in this issue. Neuroactive steroids are natural derivatives of progesterone but are proving effective as exogenous treatments. The best understood mechanism is that of positive allosteric modulation of GABA

Pralsetinib In Patients With Advanced/Metastatic Rearranged During Transfection (Ret)-Altered Thyroid Cancer: Updated Efficacy And Safety Data From The Arrow Study, Vivek Subbiah, Douglas Adkins, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Response Of Dual-Leucine Zipper Kinase (Dlk) To Nocodazole: Evidence For A Homeostatic Cytoskeletal Repair Mechanism, Laura Devault, Chase Mateusiak, John Palucki, Michael Brent, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

Genetic and pharmacological perturbation of the cytoskeleton enhances the regenerative potential of neurons. This response requires Dual-leucine Zipper Kinase (DLK), a neuronal stress sensor that is a central regulator of axon regeneration and degeneration. The damage and repair aspects of this response are reminiscent of other cellular homeostatic systems, suggesting that a cytoskeletal homeostatic response exists. In this study, we propose a framework for understanding DLK mediated neuronal cytoskeletal homeostasis. We demonstrate that low dose nocodazole treatment activates DLK signaling. Activation of DLK signaling results in a DLK-dependent transcriptional signature, which we identify through RNA-seq. This signature includes genes likely …

Shared Decision-Making During Virtual Care Regarding Rheumatologic And Chronic Conditions: Qualitative Study Of Benefits, Pitfalls, And Optimization, Lisa Zickuhr, Catherine Mccarthy, Emma Nolan-Thomas, Tiffany Westrich-Robertson, Elizabeth A Baker, Janice L Hanson

2020-Current year OA Pubs

OBJECTIVE: Virtual care (VC) is an accepted modality of care delivery, and shared decision-making (SDM) benefits patients with rheumatologic and chronic conditions (RCCs). Unfortunately, research suggests reduced quality of SDM during VC. This study explores the benefits and shortcomings of SDM regarding RCCs during VC with suggestions for optimally using VC during SDM.

METHODS: Following Stiggelbout's framework for SDM, we conducted focus groups of patients with RCCs and providers to understand their experiences with SDM during VC, probing for facilitating and challenging factors. We conducted content analysis of the transcripts, defining themes, and inductively reasoned to identify relationships among themes. …

Arid1a Loss Is Associated With Increased Nrf2 Signaling In Human Head And Neck Squamous Cell Carcinomas, Vinh Nguyen, Travis P. Schrank, Michael B. Major, Bernard E. Weissman

2020-Current year OA Pubs

Prior to the next generation sequencing and characterization of the tumor genome landscape, mutations in the SWI/SNF chromatin remodeling complex and the KEAP1-NRF2 signaling pathway were underappreciated. While these two classes of mutations appeared to independently contribute to tumor development, recent reports have demonstrated a mechanistic link between these two regulatory mechanisms in specific cancer types and cell models. In this work, we expand upon these data by exploring the relationship between mutations in BAF and PBAF subunits of the SWI/SNF complex and activation of NRF2 signal transduction across many cancer types. ARID1A/B mutations were strongly associated with NRF2 transcriptional …

Reference Ranges For Left Modified Myocardial Performance Index: Systematic Review And Meta-Analysis, Katherine H Bligard, Michelle Doering, Shay Porat, Joshua I Rosenbloom

2020-Current year OA Pubs

INTRODUCTION: The modified myocardial performance index (mod-MPI) is a noninvasive Doppler-derived metric used to evaluate fetal cardiac function. However, the reference ranges for mod-MPI in normal fetuses are not clearly defined, which limits the use of this technology in fetuses with potential cardiac compromise. Thus, we aimed to perform a systematic review and meta-analysis of published mod-MPI reference ranges across gestation.

METHODS: The published literature was systematically searched, and all published articles in any language that provided values for the left ventricular mod-MPI obtained in low-risk, singleton fetuses were considered eligible for further review. All retrieved titles and abstracts were …

Harmonization Of Csf And Imaging Biomarkers In Alzheimer's Disease: Need And Practical Applications For Genetics Studies And Preclinical Classification, Jigyasha Timsina, Muhammad Ali, Anh Do, Lihua Wang, Daniel Western, Yun Ju Sung, Carlos Cruchaga

2020-Current year OA Pubs

In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aβ), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. We used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS results using this approach with currently accepted methods. We also used a generalized mixture model to calculate the threshold for biomarker-positivity. Based on our findings, our normalization approach …

Accuracy Of True-Net In Comparison To Established White Matter Hyperintensity Segmentation Methods: An Independent Validation Study, Jeremy F Strain, Maryam Rahmani, Donna Dierker, Christopher Owen, Hussain Jafri, Andrei G Vlassenko, Kyle Womack, Jurgen Fripp, Duygu Tosun, Tammie L S Benzinger, Michael Weiner, Colin Masters, Jin-Moo Lee, John C Morris, Manu S Goyal, Adopic And Adni Investigators

2020-Current year OA Pubs

White matter hyperintensities (WMH) are nearly ubiquitous in the aging brain, and their topography and overall burden are associated with cognitive decline. Given their numerosity, accurate methods to automatically segment WMH are needed. Recent developments, including the availability of challenge data sets and improved deep learning algorithms, have led to a new promising deep-learning based automated segmentation model called TrUE-Net, which has yet to undergo rigorous independent validation. Here, we compare TrUE-Net to six established automated WMH segmentation tools, including a semi-manual method. We evaluated the techniques at both global and regional level to compare their ability to detect the …

An Overview Of The Effects Of Tenapanor On Visceral Hypersensitivity In The Treatment Of Irritable Bowel Syndrome With Constipation, Prashant Singh, Gregory S Sayuk, David P Rosenbaum, Susan Edelstein, Kenji Kozuka, Lin Chang

2020-Current year OA Pubs

BACKGROUND: Patients with irritable bowel syndrome with constipation (IBS-C) experience persistent abdominal pain, a common symptom leading to greater healthcare utilization and reports of treatment non-response. Clinically significant improvements in abdominal pain were observed in clinical trials of tenapanor, a first-in-class inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), for the treatment of IBS-C in adults.

AIM: This narrative review reports the current knowledge about visceral hypersensitivity as a mechanism for abdominal pain in patients with IBS-C and explores the published evidence for hypothesized mechanisms by which tenapanor may reduce visceral hypersensitivity leading to the observed clinical response of decreased abdominal …

Efficacy And Safety Of Bempedoic Acid In Patients With Heterozygous Familial Hypercholesterolemia: Analysis Of Pooled Patient-Level Data From Phase 3 Clinical Trials, P Barton Duell, Maciej Banach, Alberico L Catapano, Ulrich Laufs, G B John Mancini, Kausik K Ray, Christine Broestl, Yang Zhang, Lei Lei, Anne C Goldberg

2020-Current year OA Pubs

BACKGROUND: Patients with heterozygous familial hypercholesterolemia (HeFH) often cannot reach guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite multidrug therapy.

OBJECTIVE: To evaluate the efficacy and safety of bempedoic acid as an add-on therapy for lowering LDL-C in patients with HeFH.

METHODS: Pooled data from two 52-week phase 3 clinical trials of patients with atherosclerotic cardiovascular disease and/or HeFH receiving maximally tolerated statin therapy (randomized 2:1 to bempedoic acid or placebo) were analyzed by HeFH status. Endpoints included changes from baseline to week 12 (and up to week 52) in LDL-C and other lipid parameters, achievement of LDL-C goals, and safety. …

Lung Infection With Classical Klebsiella Pneumoniae Strains Establishes Robust Macrophage-Dependent Protection Against Heterologous Reinfection, Joseph J Mackel, Casey L G Mick, Emily Guo, David A Rosen

2020-Current year OA Pubs

At present, there is no approved vaccine for prevention of infection by the opportunistic bacterium Klebsiella pneumoniae (Kp); success in treating these infections is increasingly challenged by the spread of antibiotic resistance. Preclinical investigation of adaptive immunity elicited by lung infection with live classical Kp may reveal host mechanisms of protection against this pathogen. Here, we utilize multiple virulent classical Kp strains to demonstrate that following lung infection, surviving wild-type mice develop protective immunity against both homologous and heterologous (heterotypic) reinfection. For Kp strains with low capacity to disseminate from the lung, this immunity is B-cell-independent. We further demonstrate that …

Evolution Of Proton Radiation Therapy Brainstem Constraints On The Pediatric Proton/Photon Consortium Registry, Dora Correia, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: Increasing concern that brainstem toxicity incidence after proton radiation therapy might be higher than with photons led to a 2014 University of Florida (UF) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the Pediatric Proton/Photon Consortium Registry (PPCR).

MATERIAL AND METHODS: This prospective multicenter cohort study gathered data from patients under the age of 22 years enrolled on the PPCR, treated between 2002 and 2019 for primary posterior fossa brain tumors. After standardizing brainstem contours, we garnered dosimetry data and correlated those meeting the 2014 proton-specific brainstem constraint …

Ivsight As An Infusion Monitor For Patients Receiving Intravenous Therapy: An Exploratory, Unblinded, Single-Center Trial, Carlos Mejia-Chew, Brett Heuring, Jeffrey Salmons, Lori Weilmuenster, Joe Beggs, Glen Kleinschmidt, Jake Eshelman, Sai Dodda

2020-Current year OA Pubs

BACKGROUND: Intravenous (IV) infusion therapy is commonly used in health care settings. However, IV therapy at home can be challenging because it relies on the patient's ability to manage multiple medications correctly, which may lead to decreased treatment adherence.

OBJECTIVE: We aimed to assess the usability and accuracy of the IVsight monitor in capturing IV infusion data compared to manual recording.

METHODS: A prospective, single-center, usability study involving patients receiving IV infusion therapy at one of the BJC's Home Infusion suites was conducted to evaluate the accuracy, performance, and acceptability of the device IVsight as a monitor for IV infusions. …

Proceedings Of The 11th Annual Deep Brain Stimulation Think Tank: Pushing The Forefront Of Neuromodulation With Functional Network Mapping, Biomarkers For Adaptive Dbs, Bioethical Dilemmas, Ai-Guided Neuromodulation, And Translational Advancements, Kara A Johnson, Nico U F Dosenbach, Evan M Gordon, Et Al.

2020-Current year OA Pubs

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and …

Lung Lymphatic Endothelial Cells Undergo Inflammatory And Prothrombotic Changes In A Model Of Chronic Obstructive Pulmonary Disease, Anjali Trivedi, Tyler M Lu, Barbara Summers, Kihwan Kim, Alexander J Rhee, Sean Houghton, Derek E Byers, Raphaël Lis, Hasina Outtz Reed

2020-Current year OA Pubs

The lymphatic vasculature regulates lung homeostasis through drainage of fluid and trafficking of immune cells and plays a key role in the response to lung injury in several disease states. We have previously shown that lymphatic dysfunction occurs early in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) and that this is associated with increased thrombin and fibrin clots in lung lymph. However, the direct effects of CS and thrombin on lymphatic endothelial cells (LECs) in COPD are not entirely clear. Studies of the blood vasculature have shown that COPD is associated with increased thrombin …

In Vivo Measurement Of Pediatric Extracorporeal Oxygenator Insensible Losses; A Single Center Pilot Study, Tess L Suttles, John Poe, Tara M Neumayr, Ahmed S Said

2020-Current year OA Pubs

INTRODUCTION: Fluid overload on Extracorporeal Membrane Oxygenation (ECMO) is associated with worse outcomes. Previous

METHODS: Pediatric ECMO patients were approached over eleven months in the pediatric and cardiac intensive care units. The water content of the oxygenator inflow sweep gas and exhaust gas were calculated by measuring the ambient temperature and relative humidity at frequent intervals and various sweep flow.

RESULTS AND DISCUSSION: Nine subjects were enrolled, generating 431 data points. The cohort had a median age of 11 years IQR [0.83, 13], weight of 23.2 kg IQR [6.48, 44.28], and body surface area of 0.815 m

Case Report: Long-Term Follow-Up Of Patients Who Received A Fimch Vaccine For Prevention Of Recurrent Urinary Tract Infections Caused By Antibiotic Resistant Enterobacteriaceae: A Case Report Series, Elise Perer, Helen Stacey, Terri Eichorn, Heidi Hughey, Julie Lawrence, Eric Cunningham, Mark O'Neil Johnson, Kevin Bacon, Andrew Kau, Scott J Hultgren, Thomas M Hooton, Jennifer L Harris

2020-Current year OA Pubs

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status …