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Electroporation Safety Factor Of 300 Nanosecond And 10 Millisecond Defibrillation In Langendorff-Perfused Rabbit Hearts, Johanna U. Neuber, Andrei G. Pakhomov, Christian W. Zemlin

Open Access Publications

AIMS: Recently, a new defibrillation modality using nanosecond pulses was shown to be effective at much lower energies than conventional 10 millisecond monophasic shocks in ex vivo experiments. Here we compare the safety factors of 300 nanosecond and 10 millisecond shocks to assess the safety of nanosecond defibrillation.

METHODS AND RESULTS: The safety factor, i.e. the ratio of median effective doses (ED50) for electroporative damage and defibrillation, was assessed for nanosecond and conventional (millisecond) defibrillation shocks in Langendorff-perfused New Zealand white rabbit hearts. In order to allow for multiple shock applications in a single heart, a pair of needle electrodes …

Application Of A Time-Series Deep Learning Model To Predict Cardiac Dysrhythmias In Electronic Health Records, Aixia Guo, Sakima Smith, Yosef M. Khan, James R. Langabeer Ii, Randi E. Foraker

Open Access Publications

BACKGROUND: Cardiac dysrhythmias (CD) affect millions of Americans in the United States (US), and are associated with considerable morbidity and mortality. New strategies to combat this growing problem are urgently needed.

OBJECTIVES: Predicting CD using electronic health record (EHR) data would allow for earlier diagnosis and treatment of the condition, thus improving overall cardiovascular outcomes. The Guideline Advantage (TGA) is an American Heart Association ambulatory quality clinical data registry of EHR data representing 70 clinics distributed throughout the US, and has been used to monitor outpatient prevention and disease management outcome measures across populations and for longitudinal research on the …

Isolation Of Reconstructed Functional Ribonucleoprotein Complexes Of Machupo Virus, Jesse D. Pyle, Sean P.J. Whelan

Open Access Publications

Arenaviruses initiate infection by delivering a transcriptionally competent ribonucleoprotein (RNP) complex into the cytosol of host cells. The arenavirus RNP consists of the large (L) RNA-dependent RNA polymerase (RdRP) bound to a nucleoprotein (NP)-encapsidated genomic RNA (viral RNA [vRNA]) template. During transcription and replication, L must transiently displace RNA-bound NP to allow for template access into the RdRP active site. Concomitant with RNA replication, new subunits of NP must be added to the nascent complementary RNAs (cRNA) as they emerge from the product exit channel of L. Interactions between L and NP thus play a central role in arenavirus gene …

Comprehensive Characterization Of 536 Patient-Derived Xenograft Models Prioritizes Candidates For Targeted Treatment, Hua Sun, Song Cao, R. Jay Mashl, Chia-Kuei Mo, Sherri R. Davies, Tina M. Primeau, Jeremy Hoog, Jacqueline L. Mudd, Matthew A. Wyczalkowski, Reyka G. Jayasinghe, Fernanda Martins Rodrigues, Nadezhda V. Terekhanova, Yize Li, Kian-Huat Lim, Andrea Wang-Gillam, Brian A. Van Tine, Cynthia X. Ma, Katherine C. Fuh, John F. Dipersio, Julie Belmar, Jason Held, Rose Tipton, Yige Wu, Lijun Yao, Daniel Cui Zhou, Feng Chen, Shunqiang Li, Ramaswamy Govindan, Li Ding, Michael C. Wendl, Rebecca Aft, Julie K. Schwarz, Jose P. Zevallos, Sidharth V. Puram, Jingqin Luo, Ryan C. Fields, Et Al

Open Access Publications

No abstract provided.

Zika Virus Infection Of Pregnant Ifnar1-/- Mice Triggers Strain-Specific Differences In Fetal Outcomes, Ellie K. Bohm, Jennifer T. Vangorder-Braid, Anna S. Jaeger, Ryan V. Moriarty, John J. Baczenas, Natalie C. Bennett, Shelby L. O'Connor, Michael K. Fritsch, Nicole A. Fuhler, Kevin K. Noguchi, Matthew T. Aliota

Open Access Publications

Zika virus (ZIKV) is a flavivirus that causes a constellation of adverse fetal outcomes collectively termed congenital Zika syndrome (CZS). However, not all pregnancies exposed to ZIKV result in an infant with apparent defects. During the 2015 to 2016 American outbreak of ZIKV, CZS rates varied by geographic location. The underlying mechanisms responsible for this heterogeneity in outcomes have not been well defined. Therefore, we sought to characterize and compare the pathogenic potential of multiple Asian-/American-lineage ZIKV strains in an established

Lyve1+ Macrophages Of Murine Peritoneal Mesothelium Promote Omentum-Independent Ovarian Tumor Growth, Nan Zhang, Anastasiia Gainullina, Emma C. Erlich, Emily J. Onufer, Rafael S. Czepielewski, Beth A. Helmink, Brian T. Saunders, Jesse W. Williams, Bernd H. Zinselmeyer, Gwendalyn J. Randolph, Ki-Wook Kim, Et Al

Open Access Publications

Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly characterized. Here, we identified two macrophage populations (LYVE1hi MHC IIlo-hi CX3CR1gfplo/- and LYVE1lo/- MHC IIhi CX3CR1gfphi subsets) in the mesenteric and parietal mesothelial linings of the peritoneum. These macrophages resembled LYVE1+ macrophages within surface membranes of numerous organs. Fate-mapping approaches and analysis of newborn mice showed that LYVE1hi macrophages predominantly originated from embryonic-derived progenitors and were controlled by CSF1 made by Wt1+ stromal cells. Their gene expression profile closely overlapped with ovarian tumor-associated macrophages previously described in the …

Modeling Spinal Locomotor Circuits For Movements In Developing Zebrafish, Yann Roussel, Stephanie F. Gaudreau, Emily R. Kacer, Mohini Sengupta, Tuan V. Bui

Open Access Publications

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of …

Neuronal Activity In Dorsal Anterior Cingulate Cortex During Economic Choices Under Variable Action Costs, Xinying Cai, Camillo Padoa-Schioppa

Open Access Publications

The role of the dorsal anterior cingulate cortex (ACCd) in decision making has often been discussed but remains somewhat unclear. On the one hand, numerous studies implicated this area in decisions driven by effort or action cost. On the other hand, work on economic choices between goods (under fixed action costs) found that neurons in ACCd encoded only post-decision variables. To advance our understanding of the role played by this area in decision making, we trained monkeys to choose between different goods (juice types) offered in variable amounts and with different action costs. Importantly, the task design dissociated computation of …

Unbiased High-Content Screening Reveals Aβ- And Tau-Independent Synaptotoxic Activities In Human Brain Homogenates From Alzheimer's Patients And High-Pathology Controls, Hao Jiang, Thomas J. Esparza, Terrance T. Kummer, David L. Brody

Open Access Publications

Alzheimer's disease (AD) is tightly correlated with synapse loss in vulnerable brain regions. It is assumed that specific molecular entities such as Aβ and tau cause synapse loss in AD, yet unbiased screens for synaptotoxic activities have not been performed. Here, we performed size exclusion chromatography on soluble human brain homogenates from AD cases, high pathology non-demented controls, and low pathology age-matched controls using our novel high content primary cultured neuron-based screening assay. Both presynaptic and postsynaptic toxicities were elevated in homogenates from AD cases and high pathology non-demented controls to a similar extent, with more modest synaptotoxic activities in …

Diffusion Basis Spectrum Imaging Measures Anti-Inflammatory And Neuroprotective Effects Of Fingolimod On Murine Optic Neuritis, Ruimeng Yang, Tsen-Hsuan Lin, Jie Zhan, Shengsheng Lai, Chunyu Song, Peng Sun, Zezhong Ye, Michael Wallendorf, Ajit George, Anne H Cross, Sheng-Kwei Song

Open Access Publications

OBJECTIVE: To prospectively determine whether diffusion basis spectrum imaging (DBSI) detects, differentiates and quantitates coexisting inflammation, demyelination, axonal injury and axon loss in mice with optic neuritis (ON) due to experimental autoimmune encephalomyelitis (EAE), and to determine if DBSI accurately measures effects of fingolimod on underlying pathology.

METHODS: EAE was induced in 7-week-old C57BL/6 female mice. Visual acuity (VA) was assessed daily to detect onset of ON after which daily oral-treatment with either fingolimod (1 mg/kg) or saline was given for ten weeks. In vivo DBSI scans of optic nerves were performed at baseline, 2-, 6- and 10-weeks post treatment. …

Patterns Of Extrapulmonary Metastases In Sarcoma Surveillance, Zachery Hong, Patrick England, Lee Rhea, Angela Hirbe, Douglas Mcdonald, Cara A Cipriano

Open Access Publications

Soft tissue sarcomas (STS) most commonly metastasize to the lungs. Current surveillance guidelines variably recommend abdominal and pelvic imaging, but there is little evidence to support this. We sought to determine the proportion of initial pulmonary versus extrapulmonary metastases, the time to development of each, and factors to identify patients that would benefit from abdominopelvic surveillance. We retrospectively reviewed 382 patients who underwent surgical treatment for STS at a single institution. Of the 33% (126/382) of patients who developed metastases, 72% (90/126) were pulmonary, 22% (28/126) were extrapulmonary, and 6% (8/126) developed both simultaneously. Initial extrapulmonary metastases occurred later (log …

Phase Ii Study Of Dacarbazine Given With Modern Prophylactic Anti-Emetics And Growth Factor Support To Patients With Metastatic, Resistant Soft Tissue, And Bone Sarcoma, Brian Van Tine, Mia Weiss, Angela Hirbe, Peter Oppelt, Sarah Abaricia, Kathryn Trinkaus, Jingqin Luo, Shellie Berry, Tyler Ruff, Cheryl Callahan, Jacqui Toensikoetter, Jessica Ley, Marilyn Siegel, Farrokh Dehdashti, Barry Siegel, Douglas Adkins

Open Access Publications

No abstract provided.

Anesthesia For Gi Endoscopy In The Era Of Covid-19, Basavana Goudra, Preet Mohinder Singh

Open Access Publications

As a result of COVID-19, the last few weeks have necessitated a reevaluation of the sedation paradigm for gastrointestinal (GI) endoscopic procedures. Routine screening and some surveillance procedures have taken a backseat and likely to remain so until a vaccine or effective treatment becomes available. Anesthesia providers and endoscopists are required to adapt to this new reality rapidly. The general aim of sedation remains the same-patient comfort, reduced hypoxia, prevention of aspiration along with rapid recovery, and discharge. The present review focuses on necessary modification to reduce the risk of virus contagion for both patients (from health-care providers) and vice …

Reproducibility Of Hospital Rankings Based On Centers For Medicare & Medicaid Services Hospital Compare Measures As A Function Of Measure Reliability, Laurent G. Glance, David R. Nerenz, Karen E. Joynt Maddox, Bruce L. Hall, Andrew W. Dick

Open Access Publications

Importance: Unreliable performance measures can mask poor-quality care and distort financial incentives in value-based purchasing.

Objective: To examine the association between test-retest reliability and the reproducibility of hospital rankings.

Design, Setting, and Participants: In a cross-sectional design, Centers for Medicare & Medicaid Services Hospital Compare data were analyzed for the 2017 (based on 2014-2017 data) and 2018 (based on 2015-2018 data) reporting periods. The study was conducted from December 13, 2020, to September 30, 2021. This analysis was based on 28 measures, including mortality (acute myocardial infarction, congestive heart failure, pneumonia, and coronary artery bypass grafting), readmissions (acute myocardial infarction, …

A Proinflammatory Stimulus Disrupts Hippocampal Plasticity And Learning Via Microglial Activation And 25-Hydroxycholesterol, Yukitoshi Izumi, Anil G. Cashikar, Kathiresan Krishnan, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski

Open Access Publications

Inflammatory cells, including macrophages and microglia, synthesize and release the oxysterol 25-hydroxycholesterol (25HC), which has antiviral and immunomodulatory properties. Here, we examined the effects of lipopolysaccharide (LPS), an activator of innate immunity, on 25HC production in microglia, and the effects of LPS and 25HC on CA1 hippocampal synaptic plasticity and learning. In primary microglia, LPS markedly increases the expression of cholesterol 25-hydroxylase (Ch25h), the key enzyme involved in 25HC synthesis, and increases the levels of secreted 25HC. Wild-type microglia produced higher levels of 25HC than

An Absence Of Equipoise: Examining Surgeons' Decision Talk During Encounters With Women Considering Breast Cancer Surgery, Mary C. Politi, Catherine H. Saunders, Victoria F. Grabinski, Renata W. Yen, Amy E. Cyr, Marie-Anne Durand, Glyn Elwyn

Open Access Publications

Shared decision-making is recommended for decisions with multiple reasonable options, yet clinicians often subtly or explicitly guide choices. Using purposive sampling, we performed a secondary analysis of 142 audio-recorded encounters between 13 surgeons and women eligible for breast-conserving surgery with radiation or mastectomy. We trained 9 surgeons in shared decision-making and provided them one of two conversation aids; 4 surgeons practiced as usual. Based on a published taxonomy of treatment recommendations (pronouncements, suggestions, proposals, offers, assertions), we examined how surgeons framed choices with patients. Many surgeons made assertions providing information and advice (usual care 71% vs. intervention 66%; p = …

Toxoplasma Bradyzoites Exhibit Physiological Plasticity Of Calcium And Energy Stores Controlling Motility And Egress, Yong Fu, Kevin M. Brown, Nathaniel G. Jones, Silvia N.J. Moreno, L. David Sibley

Open Access Publications

No abstract provided.

Cell Death And Transcriptional Responses Induced In Larvae Of The Nematode Haemonchus Contortus By Toxins/Toxicants With Broad Phylogenetic Efficacy, Douglas P Jasmer, Bruce A Rosa, Makedonka Mitreva

Open Access Publications

Establishing methods to investigate treatments that induce cell death in parasitic nematodes will promote experimental approaches to elucidate mechanisms and to identify prospective anthelmintics capable of inducing this outcome. Here, we extended recent progress on a method to monitor cell death and to identify small molecule inhibitors in

A Comprehensive Review Of Tic Disorders In Children, Keisuke Ueda, Kevin J. Black

Open Access Publications

Tics are characterized by sudden, rapid, recurrent, nonrhythmic movement or vocalization, and are the most common movement disorders in children. Their onset is usually in childhood and tics often will diminish within one year. However, some of the tics can persist and cause various problems such as social embarrassment, physical discomfort, or emotional impairments, which could interfere with daily activities and school performance. Furthermore, tic disorders are frequently associated with comorbid neuropsychiatric symptoms, which can become more problematic than tic symptoms. Unfortunately, misunderstanding and misconceptions of tic disorders still exist among the general population. Understanding tic disorders and their comorbidities …

Toll-Like Receptor Signaling In The Establishment And Function Of The Immune System, Jahnavi Aluri, Megan A Cooper, Laura G Schuettpelz

Open Access Publications

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in …

Eruptive Xanthoma Model Reveals Endothelial Cells Internalize And Metabolize Chylomicrons, Leading To Extravascular Triglyceride Accumulation, Ainara G Cabodevilla, Songtao Tang, Sungwoon Lee, Adam E Mullick, Jose O Aleman, M Mahmood Hussain, William C Sessa, Nada A Abumrad, Ira J Goldberg

Open Access Publications

Although tissue uptake of fatty acids from chylomicrons is primarily via lipoprotein lipase (LpL) hydrolysis of triglycerides (TGs), studies of patients with genetic LpL deficiency suggest additional pathways deliver dietary lipids to tissues. Despite an intact endothelial cell (EC) barrier, hyperchylomicronemic patients accumulate chylomicron-derived lipids within skin macrophages, leading to the clinical finding eruptive xanthomas. We explored whether an LpL-independent pathway exists for transfer of circulating lipids across the EC barrier. We found that LpL-deficient mice had a marked increase in aortic EC lipid droplets before and after a fat gavage. Cultured ECs internalized chylomicrons, which were hydrolyzed within lysosomes. …

Nanoparticulate Matter Exposure Results In White Matter Damage And An Inflammatory Microglial Response In An Experimental Murine Model, Michelle Connor, Krista Lamorie-Foote, Qinghai Liu, Kristina Shkirkova, Hans Baertsch, Constantinos Sioutas, Todd E. Morgan, Caleb E. Finch, William J. Mack

Open Access Publications

Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban …

Prognostic And Pathophysiologic Significance Of Il-8 (Cxcl8) In Biliary Atresia, Nimish Godbole, Iiris Nyholm, Maria Hukkinen, Joseph R Davidson, Athanasios Tyraskis, Katja Eloranta, Noora Andersson, Jouko Lohi, Päivi Heikkilä, Antti Kyrönlahti, Marjut Pihlajoki, Mark Davenport, Markku Heikinheimo, Mikko P Pakarinen

Open Access Publications

Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed in liver utilizing quantitative polymerase chain reaction (qPCR), immunohistochemistry and in situ hybridization and in serum using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls and 68 normal controls. Results were correlated to portoenterostomy (PE) outcomes, biochemical and histological liver injury, transcriptional markers of fibrosis and cholangiocytes, and expression of other related cytokines. IL-8 …

Role Of Anesthetics And Their Adjuvants In Neurovascular Protection In Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage, Umeshkumar Athiraman, Gregory J Zipfel

Open Access Publications

Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage. Several therapies have been explored to prevent these secondary brain injury processes after aneurysmal subarachnoid hemorrhage with limited clinical success. Experimental and clinical studies have shown a neuroprotective role of certain anesthetics in cerebrovascular disorders including aneurysmal subarachnoid hemorrhage. The vast majority of aneurysmal subarachnoid hemorrhage patients require general anesthesia for surgical or …

Basophils Balance Healing After Myocardial Infarction Via Il-4/Il-13, Florian Sicklinger, Kory J Lavine, Et Al

Open Access Publications

The inflammatory response after myocardial infarction (MI) is a precisely regulated process that greatly affects subsequent remodeling. Here, we show that basophil granulocytes infiltrated infarcted murine hearts, with a peak occurring between days 3 and 7. Antibody-mediated and genetic depletion of basophils deteriorated cardiac function and resulted in enhanced scar thinning after MI. Mechanistically, we found that basophil depletion was associated with a shift from reparative Ly6Clo macrophages toward increased numbers of inflammatory Ly6Chi monocytes in the infarcted myocardium. Restoration of basophils in basophil-deficient mice by adoptive transfer reversed this proinflammatory phenotype. Cellular alterations in the absence of basophils were …

Public Preferences For Social Distancing Policy Measures To Mitigate The Spread Of Covid-19 In Missouri, Ingrid Eshun-Wilson, Aaloke Mody, Virginia Mckay, Matifadza Hlatshwayo, Cory Bradley, Vetta Thompson, David V. Glidden, Elvin H. Geng

Open Access Publications

Importance: Policies to promote social distancing can minimize COVID-19 transmission but come with substantial social and economic costs. Quantifying relative preferences among the public for such practices can inform locally relevant policy prioritization and optimize uptake.

Objective: To evaluate relative utilities (ie, preferences) for COVID-19 pandemic social distancing strategies against the hypothetical risk of acquiring COVID-19 and anticipated income loss.

Design, Setting, and Participants: This survey study recruited individuals living in the Missouri area from May to June 2020 via randomly distributed unincentivized social media advertisements and local recruitment platforms for members of minority racial and ethnic groups. Participants answered …

Strategies For Disseminating And Implementing Covid-19 Vaccines In Rural Areas, Beth Prusaczyk

Open Access Publications

The United States has well-documented rural-urban health disparities, and it is imperative that these are not exacerbated by an inefficient rollout of coronavirus disease 2019 (COVID-19) vaccines to rural areas. In addition to the preexisting barriers to delivering and receiving health care in rural areas, such as high patient:provider ratios and long geographic distances between patients and providers, rural residents are significantly more likely to say they have no intention of receiving a COVID-19 vaccine, compared with urban residents. To overcome these barriers and ensure that rural residents receive the vaccine, officials and communities should look to previous research on …

Weekend Light Shifts Evoke Persistent Drosophila Circadian Neural Network Desynchrony, Ceazar Nave, Logan Roberts, Patrick Hwu, Jerson D. Estrella, Thanh C. Vo, Thanh H. Nguyen, Tony Thai Bui, Daniel J. Rindner, Nicholas Pervolarakis, Paul J. Shaw, Tanya L. Leise, Todd C. Holmes

Open Access Publications

We developed a method for single-cell resolution longitudinal bioluminescence imaging of PERIOD (PER) protein and TIMELESS (TIM) oscillations in cultured male adult

Anesthesia For Thoracic Surgery In Infants And Children, Teresa M. Murray-Torres, Peter D. Winch, Aymen N. Naguib, Joseph D. Tobias

Open Access Publications

No abstract provided.

Effects Of Gynura Bicolor On Glycemic Control And Antioxidant Ability In Prediabetes, Chu-Hsuan Hsia, Yu-Tang Tung, Yu-Sheng Yeh, Yi-Wen Chien

Open Access Publications

No abstract provided.