Medicine and Health Sciences Commons^™

Detection Of Emerging Neurodegeneration Using Bayesian Linear Mixed-Effect Modeling, Yann Cobigo, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Early detection of neurodegeneration, and prediction of when neurodegenerative diseases will lead to symptoms, are critical for developing and initiating disease modifying treatments for these disorders. While each neurodegenerative disease has a typical pattern of early changes in the brain, these disorders are heterogeneous, and early manifestations can vary greatly across people. Methods for detecting emerging neurodegeneration in any part of the brain are therefore needed. Prior publications have described the use of Bayesian linear mixed-effects (BLME) modeling for characterizing the trajectory of change across the brain in healthy controls and patients with neurodegenerative disease. Here, we use an extension …

Fibroblast Growth Factor Receptor Signaling In Cardiomyocytes Is Protective In The Acute Phase Following Ischemia-Reperfusion Injury, Dzmitry Matsiukevich, Stacey L House, Carla Weinheimer, Attila Kovacs, David M Ornitz

2020-Current year OA Pubs

Fibroblast growth factor receptors (FGFRs) are expressed in multiple cell types in the adult heart. Previous studies have shown a cardioprotective effect of some FGF ligands in cardiac ischemia-reperfusion (I/R) injury and a protective role for endothelial FGFRs in post-ischemic vascular remodeling. To determine the direct role FGFR signaling in cardiomyocytes in acute cardiac I/R injury, we inactivated

Infantile-Onset Pompe Disease Complicated By Sickle Cell Anemia: Case Report And Management Considerations, Rodrigo Tzovenos Starosta, Ying-Chen Claire Hou, Katelyn Leestma, Prapti Singh, Luke Viehl, Linda Manwaring, Jorge Luis Granadillo, Molly C Schroeder, Jamie N Colombo, Halana Whitehead, Patricia Irene Dickson, Monica L Hulbert, Hoanh Thi Nguyen

2020-Current year OA Pubs

Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain. Here we report a case of a male newborn of African ancestry diagnosed and treated for IOPD and SCA. Molecular testing confirmed two

Environmentally-Triggered Contraction Of The Norovirus Virion Determines Diarrheagenic Potential, Emily W Helm, Elizabeth A Kennedy, Megan T Baldridge, Et Al.

2020-Current year OA Pubs

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course …

Mobility Disability And Exercise: Health Outcomes Of An Accessible Community-Based Center, Kerri A. Morgan, Kelly L Taylor, Carla Wilson Walker, Susan Tucker, Jessica L Dashner, Holly Hollingsworth

2020-Current year OA Pubs

OBJECTIVE: The purpose of this study was to determine how support and guidance provided by trained professionals during a 12-week, community-based transition exercise program, impact health outcomes and continued engagement in physical activity for persons with a mobility disability (PwMD).

DESIGN: A single arm pre-post design was used.

SETTING: Accessible community-based health and wellness center.

PARTICIPANTS: The study included 244 PwMD using a mobility device.

INTERVENTIONS: Participants completed a 12-week transition exercise program provided through an accessible community facility that provided education and support to complete endurance and strength related exercises as well as programming to encourage transition to self-directed …

Personalized Practice Dosages May Improve Motor Learning In Older Adults Compared To "Standard Of Care" Practice Dosages: A Randomized Controlled Trial, Geneviève N Olivier, Leland E Dibble, Serene S Paul, Keith R Lohse, Christopher S Walter, Ryan J Marker, Heather A Hayes, K Bo Foreman, Kevin Duff, Sydney Y Schaefer

2020-Current year OA Pubs

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one's plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages [

Modifications To Student Quarantine Policies In K-12 Schools Implementing Multiple Covid-19 Prevention Strategies Restores In-Person Education Without Increasing Sars-Cov-2 Transmission Risk, January-March 2021, Patrick Dawson, Sara Malone, Stephanie A. Fritz, Brock K. Montgomery, Mary Boyle, Brett Maricque, Albert M. Lai, Julie A. Neidich, Rachel C. Orscheln, Jason G Newland, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021.

METHODS: We conducted a prospective cohort study of COVID-19 cases and close contacts among students and staff (n = 65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. The projected number of school-based transmission events among untested close contacts was extrapolated from the percentage of events detected among tested asymptomatic close contacts and summed with the number of detected events for a …

Evaluation Of Dose-Dependent Treatment Effects After Mid-Trial Dose Escalation In Biomarker, Clinical, And Cognitive Outcomes For Gantenerumab Or Solanezumab In Dominantly Inherited Alzheimer's Disease, Guoqiao Wang, Yan Li, Chengjie Xiong, Eric Mcdade, David B Clifford, Susan L Mills, Anna M Santacruz, Andrew J Aschenbrenner, Jason Hassenstab, Tammie L S Benzinger, Brian A Gordon, Anne M Fagan, Kelley A Coalier, Jorge J Libre-Guerra, Austin Mccullough, Nelly Joseph-Mathurin, Charles D Chen, Randall J Bateman, Et Al.

2020-Current year OA Pubs

INTRODUCTION: While the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) was ongoing, external data suggested higher doses were needed to achieve targeted effects; therefore, doses of gantenerumab were increased 5-fold, and solanezumab was increased 4-fold. We evaluated to what extent mid-trial dose increases produced a dose-dependent treatment effect.

METHODS: Using generalized linear mixed effects (LME) models, we estimated the annual low- and high-dose treatment effects in clinical, cognitive, and biomarker outcomes.

RESULTS: Both gantenerumab and solanezumab demonstrated dose-dependent treatment effects (significant for gantenerumab, non-significant for solanezumab) in their respective target amyloid biomarkers (Pittsburgh compound B positron emission tomography standardized uptake …

Islet Cilia And Glucose Homeostasis, Isabella Melena, Jing W Hughes

2020-Current year OA Pubs

Diabetes is a growing pandemic affecting over ten percent of the U.S. population. Individuals with all types of diabetes exhibit glucose dysregulation due to altered function and coordination of pancreatic islets. Within the critical intercellular space in pancreatic islets, the primary cilium emerges as an important physical structure mediating cell-cell crosstalk and signal transduction. Many events leading to hormone secretion, including GPCR and second-messenger signaling, are spatiotemporally regulated at the level of the cilium. In this review, we summarize current knowledge of cilia action in islet hormone regulation and glucose homeostasis, focusing on newly implicated ciliary pathways that regulate insulin …

Multi-Omics Insights Into The Biological Mechanisms Underlying Statistical Gene-By-Lifestyle Interactions With Smoking And Alcohol Consumption, Timothy D Majarian, Mary F Feitosa, Michael Province, Dabeeru C Rao, Karen Schwander, Yun Ju Sung, C Charles Gu, Et Al.

2020-Current year OA Pubs

Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium's Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment …

The Relevance Of Rich Club Regions For Functional Outcome Post-Stroke Is Enhanced In Women, Anna K. Bonkhoff, Laura Heitsch, Chia-Ling Phuah, Et Al.

2020-Current year OA Pubs

No abstract provided.

Stat3 Gain-Of-Function Syndrome, Tiphanie P Vogel, Jennifer W Leiding, Megan A Cooper, Lisa R Forbes Satter

2020-Current year OA Pubs

STAT3 gain-of-function (GOF) syndrome is a multi-organ primary immune regulatory disorder characterized by early onset autoimmunity. Patients present early in life, most commonly with lymphoproliferation, autoimmune cytopenias, and growth delay. However, disease is often progressive and can encompass a wide range of clinical manifestations such as: enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, and rarely neurologic disease, vasculopathy, and malignancy. Treatment of the autoimmune and immune dysregulatory features of STAT3-GOF patients relies heavily on immunosuppression and is often challenging and fraught with complications including severe infections. Defects in the T cell compartment leading to effector T cell accumulation …

Do The Expert Recommendations For Implementing Change (Eric) Strategies Adequately Address Sustainment?, Nicole Nathan, Byron J Powell, Rachel C Shelton, Celia V Laur, Luke Wolfenden, Maji Hailemariam, Sze Lin Yoong, Rachel Sutherland, Melanie Kingsland, Thomas J Waltz, Alix Hall

2020-Current year OA Pubs

BACKGROUND: Sustainability science is an emerging area within implementation science. There is limited evidence regarding strategies to best support the continued delivery and sustained impact of evidence-based interventions (EBIs). To build such evidence, clear definitions, and ways to operationalize strategies specific and/or relevant to sustainment are required. Taxonomies and compilations such as the Expert Recommendations for Implementing Change (ERIC) were developed to describe and organize implementation strategies. This study aimed to adapt, refine, and extend the ERIC compilation to incorporate an explicit focus on sustainment. We also sought to classify the specific phase(s) of implementation when the ERIC strategies could …

Management Of Acute Promyelocytic Leukemia In The Setting Of Acute Covid-19 Infection, Kevin G Shim, Mallory Crain, Kristan Augustin, Karolyn A Oetjen

2020-Current year OA Pubs

Acute promyelocytic leukemia (APL) often presents with significant coagulopathy which may result in both hemorrhagic and thrombotic complications. The emergence of the COVID-19 pandemic has complicated the initial treatment and diagnosis of APL owing to the viral infection's own associated coagulopathy. Here we report two cases of APL newly diagnosed in the setting of COVID-19 infection and considerations in their management. Included is a discussion of strategies for the dosing of arsenic trioxide in patients with significant obesity and renal insufficiency. The case series submitted does not represent a study on patients and thus no specific informed consents or permissions …

Protocol For The Ketamine For Postoperative Avoidance Of Depressive Symptoms (K-Pass) Feasibility Study: A Randomized Clinical Trial, Bradley A Fritz, Bethany R Tellor Pennington, Ben J A Palanca, Julie A Schweiger, Jon T Willie, Nuri B Farber

2020-Current year OA Pubs

No abstract provided.

A Framework For Extension Studies Using Real-World Data To Examine Long-Term Safety And Effectiveness, Mehmet Burcu, Cyntia B Manzano-Salgado, Anne M Butler, Jennifer B Christian

2020-Current year OA Pubs

Understanding the long-term benefits and risks of treatments, devices, and vaccines is critically important for individual- and population-level healthcare decision-making. Extension studies, or 'roll-over studies,' are studies that allow for patients participating in a parent clinical trial to 'roll-over' into a subsequent related study to continue to observe and measure long-term safety, tolerability, and/or effectiveness. These designs are not new and are often used as an approach to satisfy regulatory post-approval safety requirements. However, designs using traditional clinical trial infrastructure can be expensive and burdensome to conduct, particularly, when following patients for many years post trial completion. Given the increasing …

Dermatologic Events Associated With The Anti-Ccr4 Antibody Mogamulizumab: Characterization And Management, Amy C M Musiek, Et Al.

2020-Current year OA Pubs

The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS). One of the most common adverse events seen with mogamulizumab in MF/SS patients is rash. Because of the protean nature of MF/SS and the variable clinical and histopathological features of mogamulizumab-associated rash, healthcare providers may have difficulty distinguishing rash from disease, and may not be aware of appropriate treatment strategies for this generally manageable adverse event. The objective of this report was to combine results from published literature with …

The Enigma Stroke Recovery Working Group: Big Data Neuroimaging To Study Brain-Behavior Relationships After Stroke, Sook-Lei Liew, Catherine E Lang, Anup K Bhattacharya, Et Al.

2020-Current year OA Pubs

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data …

Silver Jubilee: 25 Years Of The First Demonstration Of The Direct Effect Of Phosphate On The Parathyroid Cell, Jordi Bover, Adriana Dusso, Et Al.

2020-Current year OA Pubs

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO

Theta-Gamma Coupling As A Cortical Biomarker Of Brain-Computer Interface-Mediated Motor Recovery In Chronic Stroke, Nabi Rustamov, Joseph Humphries, Alexandre Carter, Eric C Leuthardt

2020-Current year OA Pubs

Chronic stroke patients with upper-limb motor disabilities are now beginning to see treatment options that were not previously available. To date, the two options recently approved by the United States Food and Drug Administration include vagus nerve stimulation and brain-computer interface therapy. While the mechanisms for vagus nerve stimulation have been well defined, the mechanisms underlying brain-computer interface-driven motor rehabilitation are largely unknown. Given that cross-frequency coupling has been associated with a wide variety of higher-order functions involved in learning and memory, we hypothesized this rhythm-specific mechanism would correlate with the functional improvements effected by a brain-computer interface. This study …

A Map Of Neurofilament Light Chain Species In Brain And Cerebrospinal Fluid And Alterations In Alzheimer's Disease, Melissa M Budelier, Yingxin He, Nicolas R Barthelemy, Hong Jiang, Yan Li, Ethan Park, Rachel L Henson, Suzanne E Schindler, David M Holtzman, Randall J Bateman

2020-Current year OA Pubs

Neurofilament light is a well-established marker of both acute and chronic neuronal damage and is increased in multiple neurodegenerative diseases. However, the protein is not well characterized in brain tissue or body fluids, and it is unknown what neurofilament light species are detected by commercial assays and whether additional species exist. We developed an immunoprecipitation-mass spectrometry assay using custom antibodies targeting various neurofilament light domains, including antibodies targeting Coil 1A/1B of the rod domain (HJ30.13), Coil 2B of the rod domain (HJ30.4) and the tail region (HJ30.11). We utilized our assay to characterize neurofilament light in brain tissue and CSF …

Combination Tigit/Pd-1 Blockade Enhances The Efficacy Of Neoantigen Vaccines In A Model Of Pancreatic Cancer, Hui Peng, Lijin Li, Chong Zuo, Michael Y Chen, Xiuli Zhang, Nancy B Myers, Graham D Hogg, David G Denardo, S Peter Goedegebuure, William G Hawkins, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Cancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.

METHODS: We used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides …

Socioecological Model-Based Design And Implementation Principles Of Lower Limb Preservation Programs As Partners For Limb-Loss Rehabilitation Programs- A Mini-Review, Vipul Khetarpaul, John P Kirby, Patrick Geraghty, John Felder, Prateek Grover

2020-Current year OA Pubs

People with lower limb loss, especially of dysvascular etiology, are at substantial risk for both ipsilateral and contralateral reamputation. Additionally, while not as well documented for reamputation, there is recognition that amputation incidence is influenced by not only sociodemographic factors such as sex, race, socioeconomic status, but also by system factors such as service access. A systems strategy to address this disparity within the field of limb-loss rehabilitation is for Limb-loss Rehabilitation Programs (LRP) to partner with medical specialists, mental health professionals, and Limb Preservation Programs (LPP) to provide comprehensive limb care. While LPPs exist around the nation, design principles …

Use Of Leishmania Major Parasites Expressing A Recombinant Trypanosoma Cruzi Antigen As Live Vaccines Against Chagas Disease, Catherine W Cai, Anne O'Shea, Christopher S Eickhoff, Hongjie Guo, Warren G Lewis, Stephen M Beverley, Daniel F Hoft

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We generated recombinant

RESULTS: We demonstrate that mice inoculated with these recombinant TS-expressing

DISCUSSION: Altogether, these data indicate that

Apoe Mediated Neuroinflammation And Neurodegeneration In Alzheimer's Disease, Samira Parhizkar, David M Holtzman

2020-Current year OA Pubs

Neuroinflammation is a central mechanism involved in neurodegeneration as observed in Alzheimer's disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, directly influences disease onset and progression by interacting with the major pathological hallmarks of AD including amyloid-β plaques, neurofibrillary tau tangles, as well as neuroinflammation. Microglia and astrocytes, the two major immune cells in the brain, exist in an immune-vigilant state providing immunological defense as well as housekeeping functions that promote neuronal well-being. It is becoming increasingly evident that under disease conditions, these immune cells become progressively dysfunctional in …

Fluorescence Imaging Of Beta Cell Primary Cilia, Zipeng A Li, Jung Hoon Cho, Louis G Woodhams, Jing W Hughes

2020-Current year OA Pubs

Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step. Ciliary abundance, distribution, and morphology are heterogeneous among islet cells and are best visualized by fluorescence microscopy, the tools for which are readily accessible to most researchers. Here we present a collection of fluorescence imaging methods …

Weakly Activated Core Neuroinflammation Pathways Were Identified As A Central Signaling Mechanism Contributing To The Chronic Neurodegeneration In Alzheimer's Disease, Fuhai Li, Abdallah M Eteleeb, William Buchser, Christopher Sohn, Guoqiao Wang, Chengjie Xiong, Philip R Payne, Eric Mcdade, Celeste M Karch, Oscar Harari, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVES: Neuroinflammation signaling has been identified as an important hallmark of Alzheimer's disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, the molecular mechanisms and biological processes of neuroinflammation remain unclear and have not well delineated using transcriptomics data available. Our objectives are to uncover the core neuroinflammation signaling pathways in AD using integrative network analysis on the transcriptomics data.

MATERIALS AND METHODS: From a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), we developed integrative and systems biology network analysis to uncover potential core neuroinflammation signaling targets …

Abnormal Synergies And Associated Reactions Post-Hemiparetic Stroke Reflect Muscle Activation Patterns Of Brainstem Motor Pathways, Laura M Mcpherson, Julius P A Dewald

2020-Current year OA Pubs

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when …

Totally Percutaneous Endovascular Repair For Ruptured Abdominal Aortic Aneurysms, Shirli Tay, Mohamed S Zaghloul, Mehreen Shafqat, Chao Yang, Kshitij A Desai, Gayan De Silva, Luis A Sanchez, Mohamed A Zayed

2020-Current year OA Pubs

PURPOSE: The PEVAR Trial demonstrated that compared to open femoral exposure, elective percutaneous endovascular AAA repair (ePEVAR) is associated with decreased perioperative morbidity and access site complications. We hypothesized that PEVAR for ruptured AAA (rPEVAR) may also improve perioperative morbidity compared to open femoral exposure (rEVAR). There are currently no reports that evaluate the utility and outcomes of rPEVAR.

MATERIALS AND METHODS: From 2015 to 2021, all patients who underwent an endovascular repair of a ruptured AAA at a single institution were included in the study and grouped into rPEVAR and rEVAR. Demographics, procedural details (successful preclose technique, conversion to …

Evaluation Of Noise Regression Techniques In Resting-State Fmri Studies Using Data Of 434 Older Adults, Norman Scheel, Jeffrey N Keller, Ellen F Binder, Eric D Vidoni, Jeffrey M Burns, Binu P Thomas, Ann M Stowe, Linda S Hynan, Diana R Kerwin, Wanpen Vongpatanasin, Heidi Rossetti, C Munro Cullum, Rong Zhang, David C Zhu

2020-Current year OA Pubs

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the "Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts" (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression …