Medicine and Health Sciences Commons^™

Epithelial Abnormalities In The Small Intestine Of Zambian Children With Stunting, Chola Mulenga, Sanja Sviben, Kanta Chandwe, Beatrice Amadi, Violet Kayamba, James A J Fitzpatrick, Victor Mudenda, Paul Kelly

2020-Current year OA Pubs

BACKGROUND: Environmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen

METHODS: We performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy.

RESULTS: Confocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes …

Functional And Phylogenetic Characterization Of Bacteria In Bovine Rumen Using Fractionation Of Ruminal Fluid, Ruth Hernández, Maryam Chaib De Mares, Hugo Jimenez, Alejandro Reyes, Alejandro Caro-Quintero

2020-Current year OA Pubs

Cattle productivity depends on our ability to fully understand and manipulate the fermentation process of plant material that occurs in the bovine rumen, which ultimately leads to the improvement of animal health and increased productivity with a reduction in environmental impact. An essential step in this direction is the phylogenetic and functional characterization of the microbial species composing the ruminal microbiota. To address this challenge, we separated a ruminal fluid sample by size and density using a sucrose density gradient. We used the full sample and the smallest fraction (5%), allowing the enrichment of bacteria, to assemble metagenome-assembled genomes (MAGs). …

Driving Performance In Older Adults: Current Measures, Findings, And Implications For Roadway Safety, Robert Toups, Theresa J Chirles, Johnathon P Ehsani, Jeffrey P Michael, John P K Bernstein, Matthew Calamia, Thomas D Parsons, David B Carr, Jeffrey N Keller

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Over 10,000 people a day turn 65 in the United States. For many older adults, driving represents an essential component of independence and is one of the most important factors in overall mobility. Recent survey studies in older adults suggest that up to 60% of older adult drivers with mild cognitive impairment, and up to 30% with dementia, continue to drive. The purpose of this review is to provide a comprehensive and detailed resource on the topics of cognition and driving for clinicians, researchers, and policymakers working on efforts related to older adult drivers.

RESEARCH DESIGN AND …

Follistatin Protein Enhances Satellite Cell Counts In Reinnervated Muscle, Mark A. Feger, Jonathan Isaacs, Satya Mallu, Dorne Yager, Mary Shall, Gaurangkumar Patel, Omar Protzuk, Akhil S Bokkisam

2020-Current year OA Pubs

No abstract provided.

Proportional Constrained Longitudinal Data Analysis Models For Clinical Trials In Sporadic Alzheimer's Disease, Guoqiao Wang, Lei Liu, Yan Li, Andrew J Aschenbrenner, Randall J Bateman, Paul Delmar, Lon S Schneider, Richard E Kennedy, Gary R Cutter, Chengjie Xiong

2020-Current year OA Pubs

INTRODUCTION: Clinical trials for sporadic Alzheimer's disease generally use mixed models for repeated measures (MMRM) or, to a lesser degree, constrained longitudinal data analysis models (cLDA) as the analysis model with time since baseline as a categorical variable. Inferences using MMRM/cLDA focus on the between-group contrast at the pre-determined, end-of-study assessments, thus are less efficient (eg, less power).

METHODS: The proportional cLDA (PcLDA) and proportional MMRM (pMMRM) with time as a categorical variable are proposed to use all the post-baseline data without the linearity assumption on disease progression.

RESULTS: Compared with the traditional cLDA/MMRM models, PcLDA or pMMRM lead to …

Role Of Tau Deposition In Early Cognitive Decline In Down Syndrome, Sigan L Hartley, Benjamin L Handen, Dana Tudorascu, Laise Lee, Annie Cohen, Brianna Piro-Gambetti, Matthew Zammit, William Klunk, Charles Laymon, Shahid Zaman, Beau M Ances, Marwan Sabbagh, Bradley T Christian

2020-Current year OA Pubs

INTRODUCTION: Drawing on the amyloid/tau/neurodegeneration (AT[N]) model, the study examined whether the tau positron emission tomography (PET) biomarker [

METHODS: Data from 123 non-demented adults with DS (

RESULTS: In models adjusting for controls, tau SUVR was negatively associated with episodic memory performance in the Aβ+ but not Aβ- group. The Aβ+/T

DISCUSSION: Similar to late-onset and autosomal dominant Alzheimer's disease (AD), high tau was an indicator of early prodromal AD in DS.

Skeletal Muscle Contractile Function In Heart Failure With Reduced Ejection Fraction - A Focus On Nitric Oxide, Lauren K Park, Andrew R Coggan, Linda R Peterson

2020-Current year OA Pubs

Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF. This review will highlight the pathologic changes in skeletal muscle in HFrEF that are related to impaired exercise performance. Next, it will discuss the key role that impaired nitric oxide (NO) bioavailability plays in HFrEF skeletal muscle pathology. Lastly, it …

Il-17 Producing Lymphocytes Cause Dry Eye And Corneal Disease With Aging In Rxrα Mutant Mouse, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Rodrigo Guimaraes De Souza, Zhiyuan Yu, Stephen C Pflugfelder

2020-Current year OA Pubs

PURPOSE: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation.

METHODS: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. The activity of RXRα ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and γδ T cells.

RESULTS: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including decreased tear …

Further Evidence That Inhibition Of Neuronal Voltage-Gated Calcium Channels Contributes To The Hypnotic Effect Of Neurosteroid Analogue, 3Β-Oh, Tamara Timic Stamenic, Francesca M Manzella, Stefan Maksimovic, Kathiresan Krishnan, Douglas F Covey, Vesna Jevtovic-Todorovic, Slobodan M Todorovic

2020-Current year OA Pubs

We recently reported that a neurosteroid analogue with T-channel-blocking properties (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH), induced hypnosis in rat pups without triggering neuronal apoptosis. Furthermore, we found that the inhibition of the Ca

Distinguishing Tumor Admixed In A Radiation Necrosis (Rn) Background: 1h And 2h Mr With A Novel Mouse Brain-Tumor/Rn Model, Xia Ge, Kyu-Ho Song, John A Engelbach, Liya Yuan, Feng Gao, Sonika Dahiya, Keith M Rich, Joseph J H Ackerman, Joel R Garbow

2020-Current year OA Pubs

PURPOSE: Distinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen (

MATERIALS AND METHODS: A pipeline of common quantitative

RESULTS: Differences in quantitative

CONCLUSIONS: These findings, employing a pipeline of quantitative

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium

Altered Peroxisome Proliferator-Activated Receptor Alpha Signaling In Variably Diseased Peripheral Arterial Segments, Connor Engel, Rodrigo Meade, Nikolai Harroun, Amanda Penrose, Mehreen Shafqat, Xiaohua Jin, Gayan Desilva, Clay Semenkovich, Mohamed Zayed

2020-Current year OA Pubs

OBJECTIVE: Peripheral atherosclerosis that accumulates in the extracranial carotid and lower extremity arteries can lead to significant morbidity and mortality. However, atherosclerotic disease progression is often not homogenous and is accelerated by diabetes. We previously observed increased phospholipid content in minimally (Min)-diseased arterial segments compared to maximally (Max)-diseased segments. Since Peroxisome Proliferator-Activated Receptor alpha (PPARα) is a key regulator of lipid metabolism, we hypothesized that it may have differential expression and signaling in Min vs. Max-diseased peripheral arterial segments.

METHODS: Eighteen patients who underwent carotid endarterectomy (CEA), and 34 patients who underwent major lower extremity amputation were prospectively enrolled into …

Leishmania Guyanensis Suppressed Inducible Nitric Oxide Synthase Provoked By Its Viral Endosymbiont, Dmitry Kopelyanskiy, Chantal Desponds, Florence Prevel, Matteo Rossi, Romain Migliorini, Tiia Snäkä, Remzi Onur Eren, Stéphanie Claudinot, Lon-Fye Lye, Manolis Pasparakis, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

Inducible nitric oxide synthase (iNOS) is essential to the production of nitric oxide (NO), an efficient effector molecule against intracellular human pathogens such as

Avoid Or Embrace? Practice Effects In Alzheimer's Disease Prevention Trials, Andrew J Aschenbrenner, Jason Hassenstab, Guoqiao Wang, Yan Li, Chengjie Xiong, Eric Mcdade, David B Clifford, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer's disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed "practice effects"). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials …

Automated Measurement Of Net Water Uptake From Baseline And Follow-Up Cts In Patients With Large Vessel Occlusion Stroke, Atul Kumar, Yasheng Chen, Aaron Corbin, Ali Hamzehloo, Amin Abedini, Zeynep Vardar, Grace Carey, Kunal Bhatia, Laura Heitsch, Jamal J Derakhshan, Jin-Moo Lee, Rajat Dhar

2020-Current year OA Pubs

Quantifying the extent and evolution of cerebral edema developing after stroke is an important but challenging goal. Lesional net water uptake (NWU) is a promising CT-based biomarker of edema, but its measurement requires manually delineating infarcted tissue and mirrored regions in the contralateral hemisphere. We implement an imaging pipeline capable of automatically segmenting the infarct region and calculating NWU from both baseline and follow-up CTs of large-vessel occlusion (LVO) patients. Infarct core is extracted from CT perfusion images using a deconvolution algorithm while infarcts on follow-up CTs were segmented from non-contrast CT (NCCT) using a deep-learning algorithm. These infarct masks …

The Chasm In Percutaneous Coronary Intervention And In-Hospital Mortality Rates Among Acute Myocardial Infarction Patients In Rural And Urban Hospitals In China: A Mediation Analysis, Miao Cai, Echu Liu, Peng Bai, Nan Zhang, Siyu Wang, Wei Li, Hualiang Lin, Xiaojun Lin

2020-Current year OA Pubs

No abstract provided.

The Past, Present, And Future Of A Human T-Cell Leukemia Virus Type 1 Vaccine, Joshua J Tu, Victoria Maksimova, Lee Ratner, Amanda R Panfil

2020-Current year OA Pubs

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus which causes a lifelong infection. An estimated 5-10 million persons are infected with HTLV-1 worldwide - a number which is likely higher due to lack of reliable epidemiological data. Most infected individuals remain asymptomatic; however, a portion of HTLV-1-positive individuals will develop an aggressive CD4+ T-cell malignancy called adult T-cell leukemia/lymphoma (ATL), or a progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Few treatment options exist for HAM/TSP outside of palliative care and ATL carries an especially poor prognosis given the heterogeneity of the disease and …

How To "Start Small And Just Keep Moving Forward": Mixed Methods Results From A Stepped-Wedge Trial To Support Evidence-Based Processes In Local Health Departments, Rebekah R Jacob, Renee G Parks, Peg Allen, Stephanie Mazzucca, Yan Yan, Sarah Kang, Debra Dekker, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Local health departments (LHDs) in the United States are charged with preventing disease and promoting health in their respective communities. Understanding and addressing what supports LHD's need to foster a climate and culture supportive of evidence-based decision making (EBDM) processes can enhance delivery of effective practices and services.

METHODS: We employed a stepped-wedge trial design to test staggered delivery of implementation supports in 12 LHDs (Missouri, USA) to expand capacity for EBDM processes. The intervention was an in-person training in EBDM and continued support by the research team over 24 months (March 2018-February 2020). We used a mixed-methods approach …

Elevated Axonal Protein Markers Following Repetitive Blast Exposure In Military Personnel, Rany Vorn, Rosanne Naunheim, Chen Lai, Chelsea Wagner, Jessica M Gill

2020-Current year OA Pubs

Blast exposures that occur during training are common in military personnel; however, the biomarkers that relate to these subtle injuries is not well understood. Therefore, the purpose of this study is to identify the acute biomarkers related to blast injury in a cohort of military personnel exposure to blast-related training. Thirty-four military personnel who participated in the training program were included in this study. Blood samples were collected before and after repetitive blast-related training on days 2 (

Use Of Implementation Mapping With Community-Based Participatory Research: Development Of Implementation Strategies Of A New Goal Setting And Goal Management Intervention System, Eunyoung Kang, Erin R Foster

2020-Current year OA Pubs

AIMS: This study aims to identify implementation determinants, mechanisms of action, implementation strategies, and implementation outcome evaluation plans for a new theory-based rehabilitation goal setting and goal management intervention system, called MyGoals, using Implementation Mapping with community-based participatory research principles.

METHODS: We completed Implementation Mapping tasks 1 to 4 as a planning team consisting of MyGoals target implementers (occupational therapists (OTs), MyGoals intervention target clients (adults with chronic conditions), and the research team. We are currently conducting mapping task 5. These processes were guided by the Consolidated Framework for Implementation Research, social cognitive theory, the taxonomy of behavior change methods, …

Crispr-Cas9 Knock-In Of T513m And G41s Mutations In The Murine Β-Galactosyl-Ceramidase Gene Re-Capitulates Early-Onset And Adult-Onset Forms Of Krabbe Disease, Rima Rebiai, Emily Rue, Steve Zaldua, Duc Nguyen, Giuseppe Scesa, Martin Jastrzebski, Robert Foster, Bin Wang, Xuntian Jiang, Leon Tai, Scott T Brady, Richard Van Breemen, Maria I Givogri, Mark S Sands, Ernesto R Bongarzone

2020-Current year OA Pubs

Krabbe Disease (KD) is a lysosomal storage disorder characterized by the genetic deficiency of the lysosomal enzyme β-galactosyl-ceramidase (GALC). Deficit or a reduction in the activity of the GALC enzyme has been correlated with the progressive accumulation of the sphingolipid metabolite psychosine, which leads to local disruption in lipid raft architecture, diffuse demyelination, astrogliosis, and globoid cell formation. The

Cryogel Scaffold-Mediated Delivery Of Adipose-Derived Stem Cells Promotes Healing In Murine Model Of Atrophic Non-Union, Katherine R Hixon, Dakota B Katz, Jennifer A Mckenzie, Anna N Miller, Farshid Guilak, Matthew J Silva

2020-Current year OA Pubs

Non-union is defined as the permanent failure of a bone to heal and occurs clinically in 5% of fractures. Atrophic non-unions, characterized by absent/minimal callus formation, are poorly understood and difficult to treat. We recently demonstrated a novel murine model of atrophic non-union in the 3.6Col1A1-tk (Col1-tk) mouse, wherein dosing with the nucleoside analog ganciclovir (GCV) was used to deplete proliferating osteoprogenitor cells, leading to a radiographic and biomechanical non-union after the mid-shaft femur fracture. Using this Col1-tk atrophic non-union model, we hypothesized that the scaffold-mediated lentiviral delivery of doxycycline-inducible BMP-2 transgenes would induce osteogenesis at the fracture site. Cryogel …

Hdl Composition, Heart Failure, And Its Comorbidities, Ahmed Diab, Carla Valenzuela Ripoll, Zhen Guo, Ali Javaheri

2020-Current year OA Pubs

Although research on high-density lipoprotein (HDL) has historically focused on atherosclerotic coronary disease, there exists untapped potential of HDL biology for the treatment of heart failure. Anti-oxidant, anti-inflammatory, and endothelial protective properties of HDL could impact heart failure pathogenesis. HDL-associated proteins such as apolipoprotein A-I and M may have significant therapeutic effects on the myocardium, in part by modulating signal transduction pathways and sphingosine-1-phosphate biology. Furthermore, because heart failure is a complex syndrome characterized by multiple comorbidities, there are complex interactions between heart failure, its comorbidities, and lipoprotein homeostatic mechanisms. In this review, we will discuss the effects of heart …

Plasma Neurofilament Light Chain Levels Are Elevated In Children And Young Adults With Wolfram Syndrome, Sarah A Eisenstein, Raveena S Boodram, Courtney L Sutphen, Heather M Lugar, Brian A Gordon, Bess A Marshall, Fumihiko Urano, Anne M Fagan, Tamara Hershey

2020-Current year OA Pubs

Wolfram syndrome is a rare disease caused by pathogenic variants in the

The Temporal Relationship Between Local School Closure And Increased Incidence Of Pediatric Diabetic Ketoacidosis, Casey K Mccluskey, Janine E Zee-Cheng, Margaret J Klein, Matthew C Scanlon, Alexandre T Rotta, Kenneth E Remy, Christopher L Carroll, Steven L Shein

2020-Current year OA Pubs

IMPORTANCE: The incidence of pediatric diabetic ketoacidosis (DKA) increased early in the COVID-19 pandemic, but the relative contribution of behavioral changes and viral-related pathophysiology are unknown.

OBJECTIVE: To evaluate the relationship between school closure date and onset of increased DKA to help clarify the etiology of the increased incidence.

DESIGN: A multi-center, quality-controlled Pediatric Intensive Care Unit (PICU) database was used to identify the number of admissions to a participating PICU with DKA on each calendar day from 60 days before local school closure to 90 days after, and compared to baseline data from the same periods in 2018-2019. Interrupted …

Modification Of Neurogenic Colonic Motor Behaviours By Chemogenetic Ablation Of Calretinin Neurons, Jing Feng, Tim J Hibberd, Jialie Luo, Pu Yang, Zili Xie, Lee Travis, Nick J Spencer, Hongzhen Hu

2020-Current year OA Pubs

How the enteric nervous system determines the pacing and propagation direction of neurogenic contractions along the colon remains largely unknown. We used a chemogenetic strategy to ablate enteric neurons expressing calretinin (CAL). Mice expressing human diphtheria toxin receptor (DTR) in CAL neurons were generated by crossing

Glial Dysfunction And Its Contribution To The Pathogenesis Of The Neuronal Ceroid Lipofuscinoses, Keigo Takahashi, Hemanth R Nelvagal, Jenny Lange, Jonathan D Cooper

2020-Current year OA Pubs

While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Genetically modified mouse models have served as a useful platform to define the disease progression in the …

Case Report: "Primary Immunodeficiency"-Severe Autoimmune Enteropathy In A Pediatric Heart Transplant Recipient Treated With Abatacept And Alemtuzumab, Elizaveta Kalaidina, Elizabeth C Utterson, Deepa Mokshagundam, Mai He, Shalini Shenoy, Megan A Cooper

2020-Current year OA Pubs

Disorders of immune dysregulation following heart transplantation in children have been reported; however, the management of such disorders remains uncertain and challenging. In this case report, we describe a clinical course of a child with severe autoimmune enteropathy after a heart transplant in infancy and detail a treatment approach with abatacept and alemtuzumab. A 21-month-old girl with a medical history of congenital dilated cardiomyopathy and heart transplantation at 2 months was evaluated for chronic hematochezia. The patient underwent an extensive workup, including endoscopic biopsy which showed crypt apoptosis, similar to that seen with graft-versus-host disease (GVHD). Results of her immune …

Low Cancer Incidence In Naked Mole-Rats May Be Related To Their Inability To Express The Warburg Effect, Pedro Freire Jorge, Matthew L Goodwin, Maurits H Renes, Maarten W Nijsten, Matthew Pamenter

2020-Current year OA Pubs

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have …

Efficacy Of Laser Interstitial Thermal Therapy (Litt) For Newly Diagnosed And Recurrent Idh Wild-Type Glioblastoma, John F De Groot, Albert H Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: Treatment options for unresectable new and recurrent glioblastoma remain limited. Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data were analyzed to determine clinical outcomes for patients with new and recurrent

METHODS: Demographics, intraprocedural data, adverse events, KPS, health economics, and survival data were prospectively collected and then analyzed on

RESULTS: A total of 29 new and 60 recurrent

CONCLUSIONS: Laser ablation is a viable option for patients with new and recurrent glioblastoma. Median OS for