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A Small Molecule P53 Activator Attenuates Fanconi Anemia Leukemic Stem Cell Proliferation, Wei Du, Xiaoli Li, Andrew F. Wilson, Qishen Pang May 2018

A Small Molecule P53 Activator Attenuates Fanconi Anemia Leukemic Stem Cell Proliferation, Wei Du, Xiaoli Li, Andrew F. Wilson, Qishen Pang

Clinical and Translational Science Institute

Although p53 mutations are common in solid tumors, such mutations are found at a lower frequency in hematologic malignancies. In the genetic disorder Fanconi anemia (FA), p53 has been proposed as an important pathophysiological factor for two important hematologic hallmarks of the disease: bone marrow failure and leukemogenesis. Here we show that low levels of the p53 protein enhance the capacity of leukemic stem cells from FA patients to repopulate immunodeficient mice. Furthermore, boosting p53 protein levels with the use of the small molecule Nutlin-3 reduced leukemia burden in recipient mice. These results demonstrate that the level of p53 protein …

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In Vivo Application Of Proton-Electron Double-Resonance Imaging, Shun Kishimoto, Murali C. Krishna, Valery V. Khramtsov, Hideo Utsumi, David J. Lurie May 2018

In Vivo Application Of Proton-Electron Double-Resonance Imaging, Shun Kishimoto, Murali C. Krishna, Valery V. Khramtsov, Hideo Utsumi, David J. Lurie

Clinical and Translational Science Institute

Significance: Proton-electron double-resonance imaging (PEDRI) employs electron paramagnetic resonance irradiation with low-field magnetic resonance imaging so that the electron spin polarization is transferred to nearby protons, resulting in higher signals. PEDRI provides information about free radical distribution and, indirectly, about the local microenvironment such as partial pressure of oxygen (pO2), tissue permeability, redox status, and acid-base balance. Recent Advances: Local acid-base balance can be imaged by exploiting the different resonance frequency of radical probes between R and RH+ forms. Redox status can also be imaged by using the loss of radical-related signal after reduction. These methods require optimized radical probes …

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In Vivo Electron Paramagnetic Resonance: Radical Concepts For Translation To The Clinical Setting, Valery V. Khramtsov May 2018

In Vivo Electron Paramagnetic Resonance: Radical Concepts For Translation To The Clinical Setting, Valery V. Khramtsov

Clinical and Translational Science Institute

Electron paramagnetic resonance (EPR)-based spectroscopic and imaging techniques allow for the study of free radicals—molecules with one or more unpaired electrons. Biological EPR applications include detection of endogenous biologically relevant free radicals as well as use of specially designed exogenous radicals to probe local microenvironments. This Forum focuses on recent advances in the field of in vivo EPR applications discussed at the International Conference on Electron Paramagnetic Resonance Spectroscopy and Imaging of Biological Systems (EPR-2017). Although direct EPR detection of endogenous free radicals such as reactive oxygen species (ROS) in vivo remains unlikely in most cases, alternative approaches based on …

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In Vivo Molecular Electron Paramagnetic Resonance-Based Spectroscopy And Imaging Of Tumor Microenvironment And Redox Using Functional Paramagnetic Probes, Valery V. Khramtsov May 2018

In Vivo Molecular Electron Paramagnetic Resonance-Based Spectroscopy And Imaging Of Tumor Microenvironment And Redox Using Functional Paramagnetic Probes, Valery V. Khramtsov

Clinical and Translational Science Institute

Significance: A key role of the tumor microenvironment (TME) in cancer progression, treatment resistance, and as a target for therapeutic intervention is increasingly appreciated. Among important physiological components of the TME are tissue hypoxia, acidosis, high reducing capacity, elevated concentrations of intracellular glutathione (GSH), and interstitial inorganic phosphate (Pi). Noninvasive in vivo pO2, pH, GSH, Pi, and redox assessment provide unique insights into biological processes in the TME, and may serve as a tool for preclinical screening of anticancer drugs and optimizing TME-targeted therapeutic strategies. Recent Advances: A reasonable radiofrequency penetration depth in living tissues and progress in development of …

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A Combined Positron Emission Tomography (Pet)-Electron Paramagnetic Resonance Imaging (Epri) System: Initial Evaluation Of A Prototype Scanner, Mark Tseytlin, Alexander V. Stolin, Priyaankadevi Guggilapu, Andrey A. Bobko, Valery V. Khramtsov, Oxana Tseytlin, Raymond R. Raylman May 2018

A Combined Positron Emission Tomography (Pet)-Electron Paramagnetic Resonance Imaging (Epri) System: Initial Evaluation Of A Prototype Scanner, Mark Tseytlin, Alexander V. Stolin, Priyaankadevi Guggilapu, Andrey A. Bobko, Valery V. Khramtsov, Oxana Tseytlin, Raymond R. Raylman

Clinical and Translational Science Institute

The advent of hybrid scanners, combining complementary modalities, has revolutionized the application of advanced imaging technology to clinical practice and biomedical research. In this project, we investigated the melding of two complementary, functional imaging methods: positron emission tomography (PET) and electron paramagnetic resonance imaging (EPRI). PET radiotracers can provide important information about cellular parameters, such as glucose metabolism. While EPR probes can provide assessment of tissue microenvironment, measuring oxygenation and pH, for example. Therefore, a combined PET/EPRI scanner promises to provide new insights not attainable with current imagers by simultaneous acquisition of multiple components of tissue microenvironments. To explore the …

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Endovascular Baroreflex Amplification For Resistant Hypertension, Monique E. A. M. Van Kleef, Mark C. Bates, Wilko Spiering May 2018

Endovascular Baroreflex Amplification For Resistant Hypertension, Monique E. A. M. Van Kleef, Mark C. Bates, Wilko Spiering

Clinical and Translational Science Institute

Purpose of review Most hypertension devices have been designed to interrupt or modify the sympathetic nervous system, which seems to be unbalanced in hypertension. Carotid baroreceptors play a pivotal role in maintaining adrenergic balance via a direct feedback interface and would be an exceptional target for intervention. The purpose of this review is to define the role of the baroreceptor in hypertension, to examine device-based therapies targeting the baroreflex and to explore future promises of endovascular baroreflex amplification (EBA). Recent findings In the last two decades, two therapeutic strategies targeting the carotid baroreceptor have evolved: baroreflex activation therapy (BAT) and …

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Kaempferol Induces G2/M Cell Cycle Arrest Via Checkpoint Kinase 2 And Promotes Apoptosis Via Death Receptors In Human Ovarian Carcinoma A2780/Cp70 Cells, Ying Gao, Junfeng Yin, Gary O. Rankin, Yi Charlie Chen May 2018

Kaempferol Induces G2/M Cell Cycle Arrest Via Checkpoint Kinase 2 And Promotes Apoptosis Via Death Receptors In Human Ovarian Carcinoma A2780/Cp70 Cells, Ying Gao, Junfeng Yin, Gary O. Rankin, Yi Charlie Chen

Clinical and Translational Science Institute

Kaempferol is a widely distributed dietary flavonoid. Epidemiological studies have demonstrated kaempferol consumption lowers the risk of ovarian cancer. Our previous research proved that kaempferol suppresses human ovarian cancer cells by inhibiting tumor angiogenesis. However, the effects of kaempferol on the cell cycle and extrinsic apoptosis of ovarian cancer cells have not yet been studied. In the present study, we demonstrated that kaempferol induced G2/M cell cycle arrest via the Chk2/Cdc25C/Cdc2 pathway and Chk2/p21/Cdc2 pathway in human ovarian cancer A2780/CP70 cells. Chk2 was not responsible for kaempferol-induced apoptosis and up-regulation of p53. Kaempferol stimulated extrinsic apoptosis via death receptors/FADD/Caspase-8 pathway. …

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Role Of Chronic Stress And Exercise On Microvascular Function In Metabolic Syndrome, Kayla W. Branyan, Evan R. Devallance, Kent A. Lemaster, R. Christopher Skinner, Randy Bryner, I. Mark Olfert, Eric E. Kelley, Jefferson C. Frisbee, Paul D. Chantler May 2018

Role Of Chronic Stress And Exercise On Microvascular Function In Metabolic Syndrome, Kayla W. Branyan, Evan R. Devallance, Kent A. Lemaster, R. Christopher Skinner, Randy Bryner, I. Mark Olfert, Eric E. Kelley, Jefferson C. Frisbee, Paul D. Chantler

Clinical and Translational Science Institute

Purpose—The present study examined the effect of unpredictable chronic mild stress (UCMS) on peripheral microvessel function in healthy and metabolic syndrome (MetS) rodents, and whether exercise training could prevent the vascular dysfunction associated with UCMS. Methods—Lean and obese (model of MetS) Zucker rats (LZR; OZR) were exposed to 8 weeks of UCMS, exercise (Ex), UCMS+Ex, or control conditions. At the end of the intervention, gracilis arterioles (GAs) were isolated and hung in a pressurized myobath to assess endotheliumdependent (EDD) and -independent (EID) dilation. Levels of nitric oxide (NO) and reactive oxygen species (ROS) were measured through DAF-FM and DHE staining, …

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Reduced Cell Division Control Protein 42 Activity Compromises Hematopoiesis-Supportive Function Of Fanconi Anemia Mesenchymal Stromal Cells, Jian Xu, Xue Li, Allison Cole, Zachary Sherman, Wei Du May 2018

Reduced Cell Division Control Protein 42 Activity Compromises Hematopoiesis-Supportive Function Of Fanconi Anemia Mesenchymal Stromal Cells, Jian Xu, Xue Li, Allison Cole, Zachary Sherman, Wei Du

Clinical and Translational Science Institute

Hematopoietic stem cells (HSCs) preserve their ability to self-renew and differentiate to different lineages in the bone marrow (BM) niche, which is composed in large part by BM stromal cells. Studies have shown that altered signaling in the BM niche results in leukemia initiation or progression. Fanconi anemia (FA) is an inherited BM failure syndrome associated with extremely high risk of leukemic transformation. By employing two FA mouse models, here we have investigated the hematopoiesis-supportive function of FA BM mesenchymal stroma cells (MSCs). We found that MSCs deficient for Fanca or Fancc gene are defective in proliferation and prone to …

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Delayed Unpaired Extinction As A Treatment For Hyperarousal Of The Rabbit Nictitating Membrane Response And Its Implications For Treating Ptsd, Bernard G. Schreurs, Carrie A. Smith-Bell, Lauren B. Burhans Apr 2018

Delayed Unpaired Extinction As A Treatment For Hyperarousal Of The Rabbit Nictitating Membrane Response And Its Implications For Treating Ptsd, Bernard G. Schreurs, Carrie A. Smith-Bell, Lauren B. Burhans

Clinical and Translational Science Institute

Treatment for PTSD (Post-traumatic stress disorder) is rarely available immediately after trauma and often delayed for weeks or months after an event. In a rabbit eyeblink conditioning model of PTSD, we have previously shown that presentations of a tone conditioned stimulus (CS) and shock unconditioned stimulus (US) in an explicitly unpaired manner known as unpaired extinction is effective in reducing CS responding and US hyperarousal even if shock intensity is reduced eight-fold and elicits only minimal responding. Here we determined if delayed delivery of unpaired extinction would still be effective in extinguishing hyperarousal. Rabbits were tested for sensitivity to shock …

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A Dedicated Breast-Pet/Ct Scanner: Evaluation Of Basic Performance Characteristics, Raymond R. Raylman, Will Van Kampen, Alexander V. Stolin, Wenbo Gong, Gangadhar Jaliparthi, Peter F. Martone, Mark F. Smith, David Sarment, Neal H. Clinthorne, Mark Perna Apr 2018

A Dedicated Breast-Pet/Ct Scanner: Evaluation Of Basic Performance Characteristics, Raymond R. Raylman, Will Van Kampen, Alexander V. Stolin, Wenbo Gong, Gangadhar Jaliparthi, Peter F. Martone, Mark F. Smith, David Sarment, Neal H. Clinthorne, Mark Perna

Clinical and Translational Science Institute

Purpose—Application of advanced imaging techniques, such as PET and x-ray CT, can potentially improve detection of breast cancer. Unfortunately, both modalities have challenges in the detection of some lesions. The combination of the two techniques, however, could potentially lead to an overall improvement in diagnostic breast imaging. The purpose of this investigation is to test the basic performance of a new dedicated breast-PET/CT. Methods—The PET component consists of a rotating pair of detectors. Its performance was evaluated using the NEMA NU4-2008 protocols. The CT component utilizes a pulsed x-ray source and flat panel detector mounted on the same gantry as …

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Nicotine And Exercise Performance: Another Tool In The Arsenal Or Curse For Anti-Doping? Eur J Appl Physiol, Toby Mündel, I. Mark Olfert Apr 2018

Nicotine And Exercise Performance: Another Tool In The Arsenal Or Curse For Anti-Doping? Eur J Appl Physiol, Toby Mündel, I. Mark Olfert

Clinical and Translational Science Institute

No abstract provided.

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Cerebrovascular Dysfunction With Stress And Depression, Emily Burrage, Kent L. Marshall, Nalini Santanam, Paul D. Chantler Apr 2018

Cerebrovascular Dysfunction With Stress And Depression, Emily Burrage, Kent L. Marshall, Nalini Santanam, Paul D. Chantler

Clinical and Translational Science Institute

Maintenance of adequate tissue perfusion through a dense network of cerebral microvessels is critical for the perseveration of normal brain function. Regulation of the cerebral blood flow has to ensure adequate delivery of nutrients and oxygen with moment-to-moment adjustments to avoid both hypo- and hyper-perfusion of the brain tissue. Even mild impairments of cerebral blood flow regulation can have significant implications on brain function. Evidence suggests that chronic stress and depression elicits multifaceted functional impairments to the cerebral microcirculation, which plays a critical role in brain health and the pathogenesis of stress-related cognitive impairment and cerebrovascular events. Identifying the functional …

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Completed Suicide In An Autopsy-Confirmed Case Of Early Onset Alzheimer's Disease, Jennifer Wiener Hartzell, Richard Geary, Kymberly Gyure, Venkata Ravi Chivukula, Marc W. Haut Apr 2018

Completed Suicide In An Autopsy-Confirmed Case Of Early Onset Alzheimer's Disease, Jennifer Wiener Hartzell, Richard Geary, Kymberly Gyure, Venkata Ravi Chivukula, Marc W. Haut

Clinical and Translational Science Institute

We report a case of a 57-year-old male with clinically diagnosed and autopsy-confirmed early onset Alzheimer’s disease who completed suicide by gunshot wound to the chest. This case has several unique aspects that have not been discussed in previous case reports of completed suicide in Alzheimer’s disease. In particular, our patient’s death was highly planned with successful compensation for his cognitive deficits. After all firearms had been removed from the home as a safety precaution, he obtained a new weapon, hid it and left himself cues to find and use it. The case is discussed in the context of literature …

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Who Owns North Carolina? Econometric, Geospatial, And Interview Analyses Of Land In Appalachian North Carolina For Land Policy Reform In The Appalachians: A Research Design And Findings To Date, Jacob Meadows Apr 2018

Who Owns North Carolina? Econometric, Geospatial, And Interview Analyses Of Land In Appalachian North Carolina For Land Policy Reform In The Appalachians: A Research Design And Findings To Date, Jacob Meadows

West Virginia Law Review

No abstract provided.

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Hydrophilic Polymer Embolism: Implications For Manufacturing, Regulation, And Postmarket Surveillance Of Coated Intravascular Medical Devices, Rashi I. Mehta, Rupal I. Mehta Mar 2018

Hydrophilic Polymer Embolism: Implications For Manufacturing, Regulation, And Postmarket Surveillance Of Coated Intravascular Medical Devices, Rashi I. Mehta, Rupal I. Mehta

Clinical and Translational Science Institute

Hydrophilic polymers are ubiquitously applied as surface coatings on catheters and intravascular medical technologies. Recent clinical literature has heightened awareness on the complication of hydrophilic polymer embolism (HPE), the phenomenon wherein polymer coating layers separate from catheter and device surfaces, and may be affiliated with a range of unanticipated adverse reactions. Significant system barriers have limited and delayed reporting on this iatrogenic complication, the full effects of which remain under-recognized by healthcare providers and manufacturers of various branded devices. In 2015, the United States Food and Drug Administration acknowledged rising clinical concerns and stated that the agency would work with …

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Nudt19 Is A Renal Coa Diphosphohydrolase With Biochemical And Regulatory Properties That Are Distinct From The Hepatic Nudt7 Isoform, Stephanie A. Shumar, Evan W. Kerr, Werner J. Geldenhuys, Grace E. Montgomery, Paolo Fagone, Puchong Thirawatananond, Harry Saavedra, Sandra B. Gabelli, Roberta Leonardi Mar 2018

Nudt19 Is A Renal Coa Diphosphohydrolase With Biochemical And Regulatory Properties That Are Distinct From The Hepatic Nudt7 Isoform, Stephanie A. Shumar, Evan W. Kerr, Werner J. Geldenhuys, Grace E. Montgomery, Paolo Fagone, Puchong Thirawatananond, Harry Saavedra, Sandra B. Gabelli, Roberta Leonardi

Clinical and Translational Science Institute

CoA is the major acyl carrier in mammals and a key cofactor in energy metabolism. Dynamic regulation of CoA in different tissues and organs supports metabolic flexibility. Two mammalian Nudix hydrolases, Nudt19 and Nudt7, degrade CoA in vitro. Nudt19 and Nudt7 possess conserved Nudix and CoA signature sequences and specifically hydrolyze the diphosphate bond of free CoA and acyl-CoAs to form 3′,5′-ADP and 4′-(acyl)phosphopantetheine. Limited information is available on these enzymes, but the relatively high abundance of Nudt19 and Nudt7 mRNA in the kidney and liver, respectively, suggests that they play specific roles in the regulation of CoA levels in …

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Food Insecurity And Behavioral Characteristics For Academic Success In Young Adults Attending An Appalachian University, Rebecca L. Hagedorn, Melissa D. Olfert Mar 2018

Food Insecurity And Behavioral Characteristics For Academic Success In Young Adults Attending An Appalachian University, Rebecca L. Hagedorn, Melissa D. Olfert

Clinical and Translational Science Institute

In order to investigate the impact of food insecurity on college students in a highly health disparate region we (1) assessed the prevalence of food insecurity among young adults at a large, rural university in Appalachia, and (2) investigated the relationship between food insecurity and behavioral characteristics including academic performance, coping strategies, and money expenditure. A cross-sectional design was used to capture a representative sample of young adults attending a large, central Appalachian university in Fall 2016. The United States Department of Agriculture (USDA) Adult Food Security Survey was used to measure food insecurity. Independent variables include money expenditure (MES), …

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In Vivo Epr Assessment Of Ph, Po2, Redox Status, And Concentrations Of Phosphate And Glutathione In The Tumor Microenvironment, Andrey A. Bobko, Timothy D. Eubank, Benoit Driesschaert, Valery V. Khramtsov Mar 2018

In Vivo Epr Assessment Of Ph, Po2, Redox Status, And Concentrations Of Phosphate And Glutathione In The Tumor Microenvironment, Andrey A. Bobko, Timothy D. Eubank, Benoit Driesschaert, Valery V. Khramtsov

Clinical and Translational Science Institute

This protocol demonstrates the capability of low-field electron paramagnetic resonance (EPR)-based techniques in combination with functional paramagnetic probes to provide quantitative information on the chemical tumor microenvironment (TME), including pO2, pH, redox status, concentrations of interstitial inorganic phosphate (Pi), and intracellular glutathione (GSH). In particular, an application of a recently developed soluble multifunctional trityl probe provides unsurpassed opportunity for in vivo concurrent measurements of pH, pO2 and Pi in Extracellular space (HOPE probe). The measurements of three parameters using a single probe allow for their correlation analyses independent of probe distribution and time of the measurements.

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Validation Of A Dietary Screening Tool In A Middle-Aged Appalachian Population, Melissa Ventura Marra, Sowmyanarayanan V. Thuppal, Elizabeth J. Johnson, Regan L. Bailey Mar 2018

Validation Of A Dietary Screening Tool In A Middle-Aged Appalachian Population, Melissa Ventura Marra, Sowmyanarayanan V. Thuppal, Elizabeth J. Johnson, Regan L. Bailey

Clinical and Translational Science Institute

Proactive nutrition screening is an effective public health strategy for identifying and targeting individuals who could benefit from making dietary improvements for primary and secondary prevention of disease. The Dietary Screening Tool (DST) was developed and validated to assess nutritional risk among rural older adults. The purpose of this study was to evaluate the utility and validity of the DST to identify nutritional risk in middle-aged adults. This cross-sectional study in middle-aged adults (45–64 year olds, n = 87) who reside in Appalachia, examined nutritional status using an online health survey, biochemical measures, anthropometry, and three representative 24-h dietary recalls. …

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Treatment For Depression And Health-Related Quality Of Life Among Adults With Arthritis, Drishti Shah, Pragya Rai, Nilanjana Dwibedi, Usha Sambamoorthi Mar 2018

Treatment For Depression And Health-Related Quality Of Life Among Adults With Arthritis, Drishti Shah, Pragya Rai, Nilanjana Dwibedi, Usha Sambamoorthi

Clinical and Translational Science Institute

Depression treatment has been proven to relieve depressive symptoms and pain and may therefore improve the health-related quality of life (HRQoL) among adults with arthritis. The objective of the current study was to examine the HRQoL associated with depression treatment among adults with arthritis and depression. A retrospective longitudinal cohort study design using data from the Medical Expenditure Panel Survey (2009–2012) was adopted. The study sample consisted of adults (≥21 years) with co-existing arthritis and depression (N = 1692). Depression treatment was categorized into: antidepressants only, psychotherapy with or without antidepressants, and neither antidepressants nor psychotherapy. Multivariable Ordinary Least Square …

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Lpa Signaling Is Regulated Through The Primary Cilium: A Novel Target In Glioblastoma, Yuriy V. Loskutov, Caryn L. Griffin, Kristina M. Marinak, Andrey Bobko, Naira V. Margaryan, Werner J. Geldenhuys, Jann N. Sarkaria, Elena N. Pugacheva Mar 2018

Lpa Signaling Is Regulated Through The Primary Cilium: A Novel Target In Glioblastoma, Yuriy V. Loskutov, Caryn L. Griffin, Kristina M. Marinak, Andrey Bobko, Naira V. Margaryan, Werner J. Geldenhuys, Jann N. Sarkaria, Elena N. Pugacheva

Clinical and Translational Science Institute

The primary cilium is a ubiquitous organelle presented on most human cells. It is a crucial signaling hub for multiple pathways including growth factor and G-protein coupled receptors. Loss of primary cilia, observed in various cancers, has been shown to affect cell proliferation. Primary cilia formation is drastically decreased in glioblastoma (GBM), however, the role of cilia in normal astrocyte or glioblastoma proliferation has not been explored. Here we report that loss of primary cilia in human astrocytes stimulates growth rate in a lysophosphatidic acid (LPA)-dependent manner. We show that lysophosphatidic acid receptor 1 (LPAR1) is accumulated in primary cilia. …

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Treating Women With Opioid Use Disorder During Pregnancy In Appalachia: Initial Neonatal Outcomes Following Buprenorphine + Naloxone Exposure, Linda Nguyen, Laura R. Lander, Kevin E. O'Grady, Patrick J. Marshalek, Adrienne Schmidt, Audra K. Kelly, Hendrée E. Jones Mar 2018

Treating Women With Opioid Use Disorder During Pregnancy In Appalachia: Initial Neonatal Outcomes Following Buprenorphine + Naloxone Exposure, Linda Nguyen, Laura R. Lander, Kevin E. O'Grady, Patrick J. Marshalek, Adrienne Schmidt, Audra K. Kelly, Hendrée E. Jones

Clinical and Translational Science Institute

Background and Objectives—Rising concerns regarding diversion and misuse of monobuprenorphine for treatment of pregnant women with opioid use disorders have sparked interest in the use of buprenorphine +naloxone to reduce misuse and diversion rates. Examined the relationship of prenatal buprenorphine +naloxone exposure to neonatal outcomes. Methods—This is a retrospective chart review of 26 mother infant dyads in comprehensive medication-assisted treatment with buprenorphine +naloxone during pregnancy. Results—All neonatal birth outcome parameters were within normal ranges, albeit on the lower side of normal for gestational age and birth weight. Only 19% of neonates required morphine pharmacology for NAS. Conclusions—Use of buprenorphine +naloxone …

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The Dosimetric Effects Of Limited Elective Nodal Irradiation In Volumetric Modulated Arc Therapy Treatment Planning For Locally Advanced Non-Small Cell Lung Cancer, Mark C. Kenamond, R. Alfredo Siochi, Malcolm D. Mattes Mar 2018

The Dosimetric Effects Of Limited Elective Nodal Irradiation In Volumetric Modulated Arc Therapy Treatment Planning For Locally Advanced Non-Small Cell Lung Cancer, Mark C. Kenamond, R. Alfredo Siochi, Malcolm D. Mattes

Clinical and Translational Science Institute

Objective—Contemporary radiotherapy guidelines for locally advanced non-small cell lung carcinoma (LA-NSCLC) recommend omitting elective nodal irradiation, despite the fact that evidence supporting this came primarily from older reports assessing comprehensive nodal coverage using 3D conformal techniques. Herein, we evaluated the dosimetric implications of the addition of limited elective nodal irradiation (LENI) to standard involved field irradiation (IFI) using volumetric modulated arc therapy (VMAT) planning. Method—Target volumes and organs-at-risk (OARs) were delineated on CT simulation images of 20 patients with LA-NSCLC. Two VMAT plans (IFI and LENI) were generated for each patient. Involved sites were treated to 60 Gy in 30 …

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The History Of Proximal Carotid Protection And Flow Reversal To Prevent Stent Angioplasty Embolization, Juan Parodi, Mark C. Bates, Takao Ohki, Claudio Schönholz Mar 2018

The History Of Proximal Carotid Protection And Flow Reversal To Prevent Stent Angioplasty Embolization, Juan Parodi, Mark C. Bates, Takao Ohki, Claudio Schönholz

Clinical and Translational Science Institute

Innovation in medicine is often driven by the observations of imaginative physicians who are blessed with insatiable curiosity, coupled with the inability to accept technical boundaries, the status quo of patient care, or the acceptance of procedural morbidity. Few examples illustrate this truism better than the physician-originated clinical research that transformed the safety of carotid stent angioplasty over the last 2 decades. Initial clinical application of carotid stenting suggested that proximal protection may be a better approach to prevent embolic stroke during the angioplasty procedure. The history of how this innovation was developed is particularly relevant as vascular surgeons adopt …

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Changes In Sensitivity To The Effects Of Atrazine On The Luteinizing Hormone Surge In Female Sprague-Dawley Rats After Repeated Daily Doses: Correlation With Liver Enzyme Expression, Charles B. Breckenridge, Chad D. Foradori, Pragati Sawhney Coder, James W. Simpkins, Robert L. Sielken Jr., Robert J. Handa Feb 2018

Changes In Sensitivity To The Effects Of Atrazine On The Luteinizing Hormone Surge In Female Sprague-Dawley Rats After Repeated Daily Doses: Correlation With Liver Enzyme Expression, Charles B. Breckenridge, Chad D. Foradori, Pragati Sawhney Coder, James W. Simpkins, Robert L. Sielken Jr., Robert J. Handa

Clinical and Translational Science Institute

Background—Atrazine suppression of the LH surge slowly develops over time and peaks after 4 days; sensitivity to atrazine decreases after 8 or 14 days of dosing. Adaptation of the LH response was correlated with increased phase I and phase II liver enzyme activity/expression. Methods—The effect of atrazine on the LH surge was evaluated in female Sprague-Dawley rats administered 100 mg/kg/day atrazine by gavage for 1, 2, 3, or 4 consecutive days or 6.5, 50, or 100 mg/kg/day atrazine for 4, 8, or 14 days. Results—No statistically significant effects of atrazine were seen on peak plasma LH or LH area under …

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Highly Metastatic K7m2 Cell Line: A Novel Murine Model Capable Of In Vivo Imaging Via Luciferase Vector Transfection, Brian T. Grisez, Justin J. Ray, Phillip A. Bostian, Justin E. Markel, Brock A. Lindsey Feb 2018

Highly Metastatic K7m2 Cell Line: A Novel Murine Model Capable Of In Vivo Imaging Via Luciferase Vector Transfection, Brian T. Grisez, Justin J. Ray, Phillip A. Bostian, Justin E. Markel, Brock A. Lindsey

Clinical and Translational Science Institute

Osteosarcoma is rare and little improvement in survival rates has occurred in the last 25 years despite modern chemotherapeutic treatment. Bioluminescent cell lines for the modeling of osteosarcoma have shown success in tracking metastases in vivo, but commonly use adenoviral vectors to transfect the native cell line with bioluminescent reporters. The purpose of this study was to develop an orthotopic model for metastatic osteosarcoma capable of in vivo monitoring of metastatic and primary tumor burden in an immunocompetent mouse and compare that model to its wild type pathogenesis. K7M2 cells were transfected using a plasmid vector and were stable after …

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Hyperspectral Imaging And K- Means Classification For Histologic Evaluation Of Ductal Carcinoma In Situ, Yasser Khouj, Jeremy Dawson, James Coad, Linda Vona-Davis Feb 2018

Hyperspectral Imaging And K- Means Classification For Histologic Evaluation Of Ductal Carcinoma In Situ, Yasser Khouj, Jeremy Dawson, James Coad, Linda Vona-Davis

Clinical and Translational Science Institute

Hyperspectral imaging (HSI) is a non-invasive optical imaging modality that shows the potential to aid pathologists in breast cancer diagnoses cases. In this study, breast cancer tissues from different patients were imaged by a hyperspectral system to detect spectral differences between normal and breast cancer tissues. Tissue samples mounted on slides were identified from 10 different patients. Samples from each patient included both normal and ductal carcinoma tissue, both stained with hematoxylin and eosin stain and unstained. Slides were imaged using a snapshot HSI system, and the spectral reflectance differences were evaluated. Analysis of the spectral reflectance values indicated that …

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Supplements, Nutrition, And Alternative Therapies For The Treatment Of Traumatic Brain Injury, Brandon P. Lucke-Wold, Aric F. Logsdon, Linda Nguyen, Ahmed Eltanahay, Ryan C. Turner, Patrick Bonasso, Chelsea Knotts, Adam Moeck, Joseph C. Maroon, Julian E. Bailes, Charles L. Rosen Feb 2018

Supplements, Nutrition, And Alternative Therapies For The Treatment Of Traumatic Brain Injury, Brandon P. Lucke-Wold, Aric F. Logsdon, Linda Nguyen, Ahmed Eltanahay, Ryan C. Turner, Patrick Bonasso, Chelsea Knotts, Adam Moeck, Joseph C. Maroon, Julian E. Bailes, Charles L. Rosen

Clinical and Translational Science Institute

Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild …

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Regulator Of G Protein Signaling-12 Modulates The Dopamine Transporter In Ventral Striatum And Locomotor Responses To Psychostimulants, Joshua D. Gross, Shane W. Kaski, Adam B. Schroer, Kimberley A. Wix, David P. Siderovski, Vincent Setola Feb 2018

Regulator Of G Protein Signaling-12 Modulates The Dopamine Transporter In Ventral Striatum And Locomotor Responses To Psychostimulants, Joshua D. Gross, Shane W. Kaski, Adam B. Schroer, Kimberley A. Wix, David P. Siderovski, Vincent Setola

Clinical and Translational Science Institute

Regulators of G protein signaling are proteins that accelerate the termination of effector stimulation after G protein-coupled receptor activation. Many regulators of G protein signaling proteins are highly expressed in the brain and therefore considered potential drug discovery targets for central nervous system pathologies; for example, here we show that RGS12 is highly expressed in microdissected mouse ventral striatum. Given a role for the ventral striatum in psychostimulant-induced locomotor activity, we tested whether Rgs12 genetic ablation affected behavioral responses to amphetamine and cocaine. RGS12 loss significantly decreased hyperlocomotion to lower doses of both amphetamine and cocaine; however, other outcomes of …

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