Medicine and Health Sciences Commons^™

Axillary Artery Fibromuscular Dysplasia In A Symptomatic Type B Aortic Dissection Causing Acute Limb Ischemia, Brian Sullivan, Nathan Droz, Vipul Khetarpaul

2020-Current year OA Pubs

Fibromuscular dysplasia (FMD) can manifest outside of its classic presentation with unusual pathology. In the present report, we have described a case of an older male patient with aortic degeneration related to acute type B dissection who had required emergent left carotid-subclavian transposition and aortic stenting. Intraoperatively, his axillary artery FMD led to acute upper extremity ischemia. The patient was treated with classic maneuvers, including balloon angioplasty, reflecting the best practices in vascular surgery. We have also discussed the diagnosis, classification, and management of FMD.

Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis And Hair Cell Function, Allison L Saettele, Hiu-Tung C Wong, Katie S Kindt, Mark E Warchol, Lavinia Sheets

2020-Current year OA Pubs

The synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO

Glycemia And Β-Cell Function Before And After Elexacaftor/Tezacaftor/Ivacaftor In Youth And Adults With Cystic Fibrosis, Christine L Chan, Andrea Granados, Amir Moheet, Sachinkumar Singh, Timothy Vigers, Ana Maria Arbeláez, Yaling Yi, Shanming Hu, Andrew W Norris, Katie Larson Ode

2020-Current year OA Pubs

BACKGROUND: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear.

METHODS: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), …

Listeria Motility Increases The Efficiency Of Epithelial Invasion During Intestinal Infection, Inge M. N. Wortel, Seonyoung Kim, Annie Y. Liu, Enid C. Ibarra, Mark J. Miller

2020-Current year OA Pubs

Listeria monocytogenes (Lm) is a food-borne pathogen that causes severe bacterial gastroenteritis, with high rates of hospitalization and mortality. Lm is ubiquitous in soil, water and livestock, and can survive and proliferate at low temperatures. Following oral ingestion of contaminated food, Lm crosses the epithelium through intestinal goblet cells in a mechanism mediated by Lm InlA binding host E-cadherin. Importantly, human infections typically occur with Lm growing at or below room temperature, which is flagellated and motile. Even though many important human bacterial pathogens are flagellated, little is known regarding the effect of Lm motility on invasion and immune evasion. …

Ubiquitin Variants Potently Inhibit Sars-Cov-2 Plpro And Viral Replication Via A Novel Site Distal To The Protease Active Site, Vera J. E. Van Vliet, Nitin Sharma, Safder S. Ganaie, Gaya K. Amarasinghe, Et Al

2020-Current year OA Pubs

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made it clear that combating coronavirus outbreaks benefits from a combination of vaccines and therapeutics. A promising drug target common to all coronaviruses-including SARS-CoV, MERS-CoV, and SARS-CoV-2-is the papain-like protease (PLpro). PLpro cleaves part of the viral replicase polyproteins into non-structural protein subunits, which are essential to the viral replication cycle. Additionally, PLpro can cleave both ubiquitin and the ubiquitin-like protein ISG15 from host cell substrates as a mechanism to evade innate immune responses during infection. These roles make PLpro an attractive antiviral drug target. Here we demonstrate that ubiquitin …

Identification Of Patients With Ovarian Cancer Experiencing The Highest Benefit From Bevacizumab In The First-Line Setting On The Basis Of Their Tumor-Intrinsic Chemosensitivity (Kelim): The Gog-0218 Validation Study, Benoit You, David Mutch, Et Al.

2020-Current year OA Pubs

PURPOSE: In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7

METHODS: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable …

Benefits Of Early Treatment With Natalizumab: A Real-World Study, Daniel Ontaneda, Ellen M Mowry, Scott D Newsome, Robert T Naismith, Jacqueline Nicholas, Elizabeth Fisher, Carl De Moor, Justin Bohn, Pei-Ran Ho, Al Sandrock, Richard Rudick, James R Williams

2020-Current year OA Pubs

BACKGROUND: The impact of early versus later high-efficacy disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) is uncertain. This study reported the association of early versus later natalizumab treatment with real-world clinical outcomes in MS patients.

METHODS: The study included 661 participants diagnosed with MS in 1994 or later from 7 US centers participating in the MS Partners Advancing Technology for Health Solutions (MS PATHS) network. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the Tysabri Outreach: Unified Commitment to Health (TOUCH) registry. Clinical outcomes were defined using neuroperformance tests included in the Multiple …

Examining Shortened Versions Of The Social Responsiveness Scale For Use In Autism Spectrum Disorder Prediction And As A Quantitative Trait Measure: Results From A Validation Study Of 3-5 Year Old Children, Kristen Lyall, Juliette Rando, Bridget Toroni, Tobechukwu Ezeh, John N Constantino, Lisa A Croen, Brigid Garvin, Kate Piselli, James Connell, Aaron J Kaat, Craig J Newschaffer, Program Collaborators For Environmental Influences On Child Health Outcomes

2020-Current year OA Pubs

BACKGROUND: The Social Responsiveness Scale (SRS) is a 65-item measure yielding a continuous score capturing autism-related traits. Scores based on SRS item subsets have been analytically examined but administration of shortened versions has not been evaluated prospectively.

OBJECTIVE: The goal of this study was to compare psychometric properties of two shortened versions of the SRS to the full 65-item SRS, in young children from both a clinical and general population setting.

METHODS: Study participants (aged 3-5 years) were drawn from the AJ Drexel Autism Institute clinic (

RESULTS: Overall, distributional properties of the three administration methods were highly comparable, with …

Fatness, Fitness And The Aging Brain: A Cross Sectional Study Of The Associations Between A Physiological Estimate Of Brain Age And Physical Fitness, Activity, Sleep, And Body Composition, David Wing, Lisa T Eyler, Eric J Lenze, Julie Loebach Wetherell, Jeanne F Nichols, Romain Meeusen, Job G Godino, Joshua S Shimony, Abraham Z Snyder, Tomoyuki Nishino, Ginger E Nicol, Guy Nagels, Bart Roelands

2020-Current year OA Pubs

INTRODUCTION: Changes in brain structure and function occur with aging. However, there is substantial heterogeneity both in terms of when these changes begin, and the rate at which they progress. Understanding the mechanisms and/or behaviors underlying this heterogeneity may allow us to act to target and slow negative changes associated with aging.

METHODS: Using T1 weighted MRI images, we applied a novel algorithm to determine the physiological age of the brain (brain-predicted age) and the predicted age difference between this physiologically based estimate and chronological age (BrainPAD) to 551 sedentary adults aged 65 to 84 with self-reported cognitive complaint measured …

Guidelines For Assessment Of Cardiac Electrophysiology And Arrhythmias In Small Animals, Crystal M Ripplinger, Stacey L Rentschler, Et Al.

2020-Current year OA Pubs

Cardiac arrhythmias are a major cause of morbidity and mortality worldwide. Although recent advances in cell-based models, including human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), are contributing to our understanding of electrophysiology and arrhythmia mechanisms, preclinical animal studies of cardiovascular disease remain a mainstay. Over the past several decades, animal models of cardiovascular disease have advanced our understanding of pathological remodeling, arrhythmia mechanisms, and drug effects and have led to major improvements in pacing and defibrillation therapies. There exist a variety of methodological approaches for the assessment of cardiac electrophysiology and a plethora of parameters may be assessed with each approach. …

A Systematic Scoping Review Of Faropenem And Other Oral Penems: Treatment Of Enterobacterales Infections, Development Of Resistance And Cross-Resistance To Carbapenems, Sumanth Gandra, Satoshi Takahashi, Fanny S Mitrani-Gold, Aruni Mulgirigama, Diogo A Ferrinho

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance is an urgent global healthcare concern. Beyond carbapenems as broad-spectrum, often 'last resort' antibiotics, oral penem antibiotics currently are approved only in Japan and India, used for the treatment of indications including urinary tract infections (UTIs). Exploring oral penem use to better understand the impact of antibiotic resistance on public health would help inform the management of infectious diseases, including UTIs.

SCOPING REVIEW METHODOLOGY: This scoping review investigated the impact of faropenem and other oral penems on Enterobacterales infection treatment and evaluated evidence for faropenem resistance and cross-resistance to carbapenems. PubMed, Embase, J-STAGE and CiNii were searched …

Immune Checkpoint Inhibitor Therapy And Outcomes From Sars-Cov-2 Infection In Patients With Cancer: A Joint Analysis Of Oncovid And Esmo-Cocare Registries, Alessio Cortellini, Gino M Dettorre, Et Al.

2020-Current year OA Pubs

BACKGROUND: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.

METHODS: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.

FINDINGS: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 …

Hiv Care Experiences And Health Priorities During The First Wave Of Covid-19: Clients' Perspectives - A Qualitative Study In Lusaka, Zambia, Njekwa Mukamba, Anjali Sharma, Chanda Mwamba, Herbert Nyirenda, Marksman Foloko, Kasapo Lumbo, Katerina Christopoulos, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Elvin H Geng, Izukanji Sikazwe, Carolyn Bolton-Moore, Laura K Beres

2020-Current year OA Pubs

BACKGROUND: The novel COVID-19 pandemic threatened to disrupt access to human immunodeficiency (HIV) treatment for persons living with HIV (PLHIV), two-thirds of whom live in sub-Saharan Africa. To inform a health system response supportive of continuity of care, we sought to understand clients' HIV care experiences and health priorities during the first wave of COVID-19 outbreak in Lusaka, Zambia.

METHODS: Leveraging a study cohort of those who completed periodic SMS surveys on HIV care, we purposefully sampled 25 PLHIV after first confirmed COVID-19 case was reported in Zambia on 18

RESULTS: All participants were aware of COVID-19, and HIV care …

Fgfr2b Signalling Restricts Lineage-Flexible Alveolar Progenitors During Mouse Lung Development And Converges In Mature Alveolar Type 2 Cells, Matthew R Jones, Arun Lingampally, Negah Ahmadvand, Lei Chong, Jin Wu, Jochen Wilhem, Ana Ivonne Vazquez-Armendariz, Meshal Ansari, Susanne Herold, David M Ornitz, Herbert B Schiller, Cho-Ming Chao, Jin-San Zhang, Gianni Carraro, Saverio Bellusci

2020-Current year OA Pubs

The specification, characterization, and fate of alveolar type 1 and type 2 (AT1 and AT2) progenitors during embryonic lung development are poorly defined. Current models of distal epithelial lineage formation fail to capture the heterogeneity and dynamic contribution of progenitor pools present during early development. Furthermore, few studies explore the pathways involved in alveolar progenitor specification and fate. In this paper, we build upon our previously published work on the regulation of airway epithelial progenitors by fibroblast growth factor receptor 2b (FGFR2b) signalling during early (E12.5) and mid (E14.5) pseudoglandular stage lung development. Our results suggest that a significant proportion …

Gantenerumab: An Anti-Amyloid Monoclonal Antibody With Potential Disease-Modifying Effects In Early Alzheimer's Disease, Randall J Bateman, Jeffrey Cummings, Scott Schobel, Stephen Salloway, Bruno Vellas, Mercè Boada, Sandra E Black, Kaj Blennow, Paulo Fontoura, Gregory Klein, Sheila Seleri Assunção, Janice Smith, Rachelle S Doody

2020-Current year OA Pubs

BACKGROUND: This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal …

Clinical Management Of Supratentorial Non-Skull Case Meningiomas, Adefisayo Adekanmbi, Mark W Youngblood, Constantine L Karras, Ephraim A Oyetunji, John Kalapurakal, Craig M Horbinski, Hinda Najem, Virginia B Hill, James P Chandler, Amy B Heimberger, Stephen T Magill, Rimas V Lukas

2020-Current year OA Pubs

Supratentorial non-skull base meningiomas are the most common primary central nervous system tumor subtype. An understanding of their pathophysiology, imaging characteristics, and clinical management options will prove of substantial value to the multi-disciplinary team which may be involved in their care. Extensive review of the broad literature on the topic is conducted. Narrowing the scope to meningiomas located in the supratentorial non-skull base anatomic location highlights nuances specific to this tumor subtype. Advances in our understanding of the natural history of the disease and how findings from both molecular pathology and neuroimaging have impacted our understanding are discussed. Clinical management …

Single-Cell Rna Sequencing Identifies A Paracrine Interaction That May Drive Oncogenic Notch Signaling In Human Adenoid Cystic Carcinoma, Anuraag S. Parikh, Avishai Wizel, Daniel Davis, Armida Lefranc-Torres, Alejandro I. Rodarte-Rascon, Lauren E. Miller, Kevin S. Emerick, Mark A. Varvares, Daniel G. Deschler, William C. Faquin, Jon C. Aster, Derrick T. Lin, Bradley E. Bernstein, Yotam Drier, Sidharth V. Puram

2020-Current year OA Pubs

Salivary adenoid cystic carcinoma (ACC) is a rare, biologically unique biphasic tumor that consists of malignant myoepithelial and luminal cells. MYB and Notch signaling have been implicated in ACC pathophysiology, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilize single-cell RNA sequencing to profile human head and neck ACC, including a comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering diversity in myoepithelial and luminal cell expression. We find differential expression of Notch ligands DLL1, JAG1, and JAG2 in …

Non-Standard Viral Genome-Derived Rna Activates Tlr3 And Type I Ifn Signaling To Induce Cdc1-Dependent Cd8+ T-Cell Responses During Vaccination In Mice, Devin G Fisher, Victoria Gnazzo, David J Holthausen, Carolina B López

2020-Current year OA Pubs

There is a critical need to develop vaccine adjuvants that induce robust immune responses able to protect against intracellular pathogens, including viruses. Previously, we described defective viral genome-derived oligonucleotides (DDOs) as novel adjuvants that strongly induce type 1 immune responses, including protective Th1 CD4+ T-cells and effector CD8+ T-cells in mice. Here, we unravel the early innate response required for this type 1 immunity induction. Upon DDO subcutaneous injection, type 1 conventional dendritic cells (cDC1s) accumulate rapidly in the draining lymph node in a Toll-like receptor 3 (TLR3)- and type I interferon (IFN)-dependent manner. cDC1 accumulation in the lymph node …

Comprehensive Transcriptomic Analysis Of Vista In Acute Myeloid Leukemia: Insights Into Its Prognostic Value, Simona Pagliuca, Carmelo Gurnari, Keman Zhang, Tariq Kewan, Waled Bahaj, Minako Mori, Ishani Nautiyal, Marie Thérèse Rubio, Francesca Ferraro, Jaroslaw P Maciejewski, Li Wang, Valeria Visconte

2020-Current year OA Pubs

The V-domain Ig suppressor of T-cell activation (VISTA) has been recognized as a critical negative regulator of antitumor immune response and is gaining growing interest as a potential pharmacological target in immunotherapy. This molecule is highly expressed in hematopoietic stem cells and myeloid compartment, and it has been found upmodulated in acute myeloid leukemia (AML). However, VISTA-associated immune features are relatively unexplored in myeloid malignancies. Herein, we aimed to explore whether this immune checkpoint regulator could play a role in the generation of an immune escape environment in AML patients. We characterized VISTA mRNA expression levels in leukemia cell lines …

Immune Phenotypes That Are Associated With Subsequent Covid-19 Severity Inferred From Post-Recovery Samples, Thomas Liechti, Yaser Iftikhar, Massimo Mangino, Margaret Beddall, Charles W Goss, Jane A O'Halloran, Philip A Mudd, Mario Roederer

2020-Current year OA Pubs

Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry. We measure the cells of the peripheral immune system from individuals who recovered from mild, moderate, severe or critical COVID-19 and focused only on those immune signatures returning to steady-state. Individuals that suffered from severe COVID-19 show reduced frequencies of T cell, mucosal-associated invariant T cell (MAIT) and dendritic …

Determining Epigenetic Memory In Kidney Proximal Tubule Cell Derived Induced Pluripotent Stem Cells Using A Quadruple Transgenic Reprogrammable Mouse, Gabriel Khelifi, Theresa Chow, Jennifer Whiteley, Victoire Fort, Benjamin D Humphreys, Samer M I Hussein, Ian M Rogers

2020-Current year OA Pubs

The majority of nucleated somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs). The process of reprogramming involves epigenetic remodelling to turn on pluripotency-associated genes and turn off lineage-specific genes. Some evidence shows that iPSCs retain epigenetic marks of their cell of origin and this "epigenetic memory" influences their differentiation potential, with a preference towards their cell of origin. Here, we reprogrammed proximal tubule cells (PTC) and tail tip fibroblasts (TTF), from a reprogrammable mouse to iPSCs and differentiated the iPSCs to renal progenitors to understand if epigenetic memory plays a role in renal differentiation. This model allowed …

Premature Ovarian Insufficiency In Clpb Deficiency: Transcriptomic, Proteomic And Phenotypic Insights, Elena J Tucker, Julia T Warren, Et Al.

2020-Current year OA Pubs

CONTEXT: Premature ovarian insufficiency (POI) is a common form of female infertility that usually presents as an isolated condition but can be part of various genetic syndromes. Early diagnosis and treatment of POI can minimize comorbidity and improve health outcomes.

OBJECTIVE: We aimed to determine the genetic cause of syndromic POI, intellectual disability, neutropenia, and cataracts.

METHODS: We performed whole-exome sequencing (WES) followed by functional validation via RT-PCR, RNAseq, and quantitative proteomics, as well as clinical update of previously reported patients with variants in the caseinolytic peptidase B (CLPB) gene.

RESULTS: We identified causative variants in CLPB, encoding a mitochondrial …

Stakeholder Engagement In Eight Comparative Effectiveness Trials In African Americans And Latinos With Asthma, Tiffany Dy, Winifred J Hamilton, C Bradley Kramer, Andrea Apter, Jerry A Krishnan, James W Stout, Stephen J Teach, Alex Federman, John Elder, Tyra Bryant-Stephens, Rebecca J Bruhl, Shawni Jackson, Kaharu Sumino

2020-Current year OA Pubs

BACKGROUND: The effects of stakeholder engagement, particularly in comparative effectiveness trials, have not been widely reported. In 2014, eight comparative effectiveness studies targeting African Americans and Hispanics/Latinos with uncontrolled asthma were funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its Addressing Disparities Program. Awardees were required to meaningfully involve patients and other stakeholders. Using specific examples, we describe how these stakeholders substantially changed the research protocols and in other ways participated meaningfully as full partners in the development and conduct of the eight studies.

METHODS: Using the method content analysis of cases, we identified themes regarding the …

Wakeful Rest Benefits Recall, But Not Recognition, Of Incidentally Encoded Memory Stimuli In Younger And Older Adults, Peter R Millar, David A Balota

2020-Current year OA Pubs

Older adults exhibit deficits in episodic memory tasks, which have often been attributed to encoding or retrieval deficits, with little attention to consolidation mechanisms. More recently, researchers have attempted to measure consolidation in the context of a behavioral experiment using the wakeful rest paradigm (i.e., a brief, quiet period of minimal stimulation, which facilitates memory performance, compared to a distractor task). Critically, older adults might not produce this effect, given established age differences in other episodic memory processes and mind-wandering. In three experiments, we directly compared younger and older adults in modified versions of the wakeful rest paradigm. Critically, we …

Csf Tau Microtubule-Binding Region Identifies Pathological Changes In Primary Tauopathies, Kanta Horie, Nicolas R Barthélemy, Yingxin He, Albert A Davis, Celeste M Karch, Richard J Perrin, Rama K Koppisetti, Faris Shaikh, Nupur Ghoshal, Randall J Bateman, Chihiro Sato, Et Al.

2020-Current year OA Pubs

Despite recent advances in fluid biomarker research in Alzheimer's disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau

Mahpic Malaria Systems Biology Data From Plasmodium Cynomolgi Sporozoite Longitudinal Infections In Macaques, Jeremy D Debarry, Xuntian Jiang, Daniel S Ory, Et Al.

2020-Current year OA Pubs

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for …

Cortex-Wide Response Mode Of Vip-Expressing Inhibitory Neurons By Reward And Punishment, Zoltán Szadai, Hyun-Jae Pi, Quentin Chevy, Katalin Ócsai, Dinu F Albeanu, Balázs Chiovini, Gergely Szalay, Gergely Katona, Adam Kepecs, Balázs Rózsa

2020-Current year OA Pubs

Neocortex is classically divided into distinct areas, each specializing in different function, but all could benefit from reinforcement feedback to inform and update local processing. Yet it remains elusive how global signals like reward and punishment are represented in local cortical computations. Previously, we identified a cortical neuron type, vasoactive intestinal polypeptide (VIP)-expressing interneurons, in auditory cortex that is recruited by behavioral reinforcers and mediates disinhibitory control by inhibiting other inhibitory neurons. As the same disinhibitory cortical circuit is present virtually throughout cortex, we wondered whether VIP neurons are likewise recruited by reinforcers throughout cortex. We monitored VIP neural activity …

Muscle-Specific Ablation Of Glucose Transporter 1 (Glut1) Does Not Impair Basal Or Overload-Stimulated Skeletal Muscle Glucose Uptake, Shawna L Mcmillin, Parker L Evans, William M Taylor, Luke A Weyrauch, Tyler J Sermersheim, Steven S Welc, Monique R Heitmeier, Richard C Hresko, Paul W Hruz, Francoise Koumanov, Geoffrey D Holman, E Dale Abel, Carol A Witczak

2020-Current year OA Pubs

Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle [

Multilevel Correlates Of Domain-Specific Physical Activity Among Rural Adults - A Cross-Sectional Study, Alan M Beck, Natalicio H Serrano, Audrey Toler, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Increasing physical activity (PA) in rural communities is a vital prevention tactic in multiple chronic diseases; however, little is known on the multilevel correlates of PA rural areas. A better understanding of domain-specific PA adds context for promoting PA in rural communities. The current study sought to determine factors associated with domain-specific and overall moderate-vigorous physical activity (MVPA) in rural communities.

METHODS: Surveys were conducted across 14 rural mid-Western communities, with the final analytical sample including 1241 adults (ages 19-96, M = 57.0 [SD = 16.7], 67.8% female, 83.8% white). Generalized linear models with negative binomial distributions examined the …

Dose-Dependent Von Willebrand Factor Inhibition By Aptamer Bb-031 Correlates With Thrombolysis In A Microfluidic Model Of Arterial Occlusion, Susan M Shea, Kimberly A Thomas, Rassam M G Rassam, Emily P Mihalko, Christina Daniel, Bruce A Sullenger, Philip C Spinella, Shahid M Nimjee

2020-Current year OA Pubs

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational …