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A Clinical Practice Guideline For The Management Of Patients With Acute Spinal Cord Injury: Recommendations On The Use Of Methylprednisolone Sodium Succinate, Michael G. Fehlings, Jefferson R. Wilson, Lindsay A. Tetreault, Bizhan Aarabi, Paul A. Anderson, Paul M. Arnold, Darrel S. Brodke, Anthony S. Burns, Kazuhiro Chiba, Joseph R. Dettori, Julio C. Furlan, Gregory W. Hawryluk, Langston T. Holly, Susan Howley, Tara Jeji, Sukhvinder Kalsi-Ryan, Mark R. Kotter, Shekar N. Kurpad, Brian Kwon, Ralph J. Marino, Allan R. Martin, Eric M. Massicotte, Geno J. Merli, James W. Middleton, Hiroaki Nakashima, Narihito Nagoshi, Katherine Palmieri, Andrea C. Skelly, Anoushka Singh, Eve Tsai, Alexander R. Vaccaro, Albert Yee, James S. Harrop

Department of Rehabilitation Medicine Faculty Papers

Introduction: The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.” Results: The main conclusions …

Probing The Metabolic Phenotype Of Breast Cancer Cells By Multiple Tracer Stable Isotope Resolved Metabolomics, Andrew N. Lane, Julie Tan, Yali Wang, Jun Yan, Richard M. Higashi, Teresa W. -M. Fan

Center for Environmental and Systems Biochemistry Faculty Publications

Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using ¹³C₆-glucose, ¹³C-1+2-glucose, ¹³C₅,¹⁵N₂-Gln, ¹³C₃-glycerol, and ¹³C₈-octanoate as tracers. These tracers were designed to probe the central energy producing …

A Clinical Practice Guideline For The Management Of Patients With Acute Spinal Cord Injury And Central Cord Syndrome: Recommendations On The Timing (≤24 Hours Versus >24 Hours) Of Decompressive Surgery, Michael G. Fehlings, Lindsay A. Tetreault, Jefferson R. Wilson, Bizhan Aarabi, Paul Anderson, Paul M. Arnold, Darrel S. Brodke, Anthony S. Burns, Kazuhiro Chiba, Joseph R. Dettori, Julio C. Furlan, Gregory Hawryluk, Langston T. Holly, Susan Howley, Tara Jeji, Sukhvinder Kalsi-Ryan, Mark Kotter, Shekar Kurpad, Ralph J. Marino, Allan R. Martin, Eric Massicotte, Geno J. Merli, James W. Middleton, Hiroaki Nakashima, Narihito Nagoshi, Katherine Palmieri, Anoushka Singh, Andrea C. Skelly, Eve C. Tsai, Alexander R. Vaccaro, Albert Yee, James S. Harrop

Department of Rehabilitation Medicine Faculty Papers

Objective: To develop recommendations on the timing of surgical decompression in patients with traumatic spinal cord injury (SCI) and central cord syndrome. Methods: A systematic review of the literature was conducted to address key relevant questions. A multidisciplinary guideline development group used this information, along with their clinical expertise, to develop recommendations for the timing of surgical decompression in patients with SCI and central cord syndrome. Based on GRADE, a strong recommendation is worded as “we recommend,” whereas a weak recommendation is presented as “we suggest.” Results: Conclusions from the systematic review included (1) isolated studies reported statistically significant and …

Oncolog, Volume 62, Number 09, September 2017, Joe Munch, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Laser Interstitial Thermal Therapy for Spinal Metastases: Laser technique may be alternative to open surgery prior to stereotactic radiation therapy for metastases adjacent to the spinal cord.
• Immunotherapy Plus Targeted Therapy for Anaplastic Thyroid Cancer: Trial combines atezolizumab with targeted or cytotoxic agents for patients with anaplastic or poorly differentiated thyroid cancer.
• A New era in Follicular Lymphoma: Newly approved drugs, clinical trials represent shift from cytotoxic to targeted and immunotherapeutic agents.
• HOUSE CALL: Understanding Clinical Trials- Trials provide access to new cancer treatments
• INBRIEF: Repeat Surgery for Close Margins May Be Unnecessary for DCIS Patients Receiving Radiation Therapy

Brain Injury-Induced Synaptic Reorganization In Hilar Inhibitory Neurons Is Differentially Suppressed By Rapamycin, Corwin R. Butler, Jeffery A. Boychuk, Bret N. Smith

Physiology Faculty Publications

Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in …

Timing Of Decompression In Patients With Acute Spinal Cord Injury: A Systematic Review, Jefferson R. Wilson, Lindsay A. Tetreault, Brian Kwon, Paul M. Arnold, Thomas E. Mroz, Christopher I. Shaffrey, James S. Harrop, Jens R. Chapman, Steven Casha, Andrea C. Skelly, Haley K. Holmer, Erika D. Brodt, Michael G. Fehlings

Department of Neurosurgery Faculty Papers

Study Design: Systematic review. Objective: To conduct a systematic review and synthesis of the literature to assess the comparative effectiveness, safety, and cost-effectiveness of early (≤24 hours) versus late decompression (>24 hours) in adults with acute spinal cord injury (SCI). Methods: A systematic search was conducted of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar to identify studies published through November 6, 2014. Studies published in any language, in humans, and with an abstract were considered for inclusion. Included studies were critically appraised and the overall strength of evidence was determined using methods proposed by the Grading of …

Strain Specific Effects Of Low Level Lead Exposure On Associative Learning And Memory In Rats., Megha Verma, J. S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Exposure to lead (Pb) remains a significant public health concern. Lead exposure in early life impairs the normal development of numerous cognitive and neurobehavioral processes. Previous work has shown that the effects of developmental Pb exposure on gene expression patterns in the brain are modulated by various factors including the developmental timing of the exposure, level of exposure, sex, and genetic background. Using gene microarray profiling, we previously reported a significant strain-specific effect of Pb exposure on the hippocampal transcriptome, with the greatest number of differentially expressed transcripts in Long Evans (LE) rats and the fewest in Sprague Dawley (SD) …

Cross-Reactive Immunity To Porcine Reproductive And Respiratory Syndrome Virus And Its Contribution To Protection, Ignacio Correas

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Due to the vast geographical distribution and significant economic losses generated, porcine reproductive and respiratory syndrome virus (PRRSV) can be considered the most important swine pathogen of contemporary times. Current control and eradication strategies against PRRSV have difficulty succeeding because of their complex nature and the absence of an effective vaccine. A major obstacle for PRRSV vaccine development is the broad heterogeneity of the virus, both at the genetic and antigenic level, its rapid evolution, and an incomplete knowledge of the immune responses responsible for clearing the virus from the host. Specifically, how known correlates of protection against PRRSV—neutralizing antibodies …

Efficacy, Safety, And Timing Of Anticoagulant Thromboprophylaxis For The Prevention Of Venous Thromboembolism In Patients With Acute Spinal Cord Injury: A Systematic Review, Paul M. Arnold, James S. Harrop, Geno J. Merli, Lindsay G. Tetreault, Brain K. Kwon, Steve Casha, Katherine Palmieri, Jefferson R. Wilson, Michael G. Fehlings, Haley K. Holmer, Daniel C. Norvell

Department of Neurosurgery Faculty Papers

Study Design: Systematic review. Objectives: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to …

Impact Of Baseline Magnetic Resonance Imaging On Neurologic, Functional, And Safety Outcomes In Patients With Acute Traumatic Spinal Cord Injury, Shekar N. Kurpad, Allan R. Martin, Lindsay A. Tetreault, Dena J. Fischer, Andrea C. Skelly, David J. Mikulis, Adam E. Flanders, Bizhan Aarabi, Thomas E. Mroz, Eve Tsai, Michael G. Fehlings

Department of Radiology Faculty Papers

Study Design: Systematic review. Objective: To perform a systematic review to evaluate the utility of magnetic resonance imaging (MRI) in patients with acute spinal cord injury (SCI). Methods: An electronic search of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar was conducted for literature published through May 12, 2015, to answer key questions associated with the use of MRI in patients with acute SCI. Results: The literature search yielded 796 potentially relevant citations, 8 of which were included in this review. One study used MRI in a protocol to decide on early surgical decompression. The MRI-protocol group showed improved …

Celiprolol: A Unique Selective Adrenoceptor Modulator, James Nawarskas, Angela Cheng-Lai, William H. Frishman

NYMC Faculty Publications

Celiprolol is a β-blocker with a unique pharmacologic profile: it is a β1-andrenoceptor antagonist with partial β2 agonist activity. Given this combination of effects, celiprolol may be better described as a selective adrenoreceptor modulator. It has antihypertensive and antianginal properties and is indicated for those uses in various countries around the world. In the United States, however, the proposed indication for this drug will be for the treatment of vascular type Ehlers-Danlos syndrome, a rare connective tissue disorder characterized by fragile arterial structure and an increased risk of life-threatening vascular complications. By reducing heart rate and pulsatile pressure, celiprolol may …

Bronchoscopic Management Of Prolonged Air Leak, S Keshishyan, A Revelo, Oleg Epelbaum

NYMC Faculty Publications

Bronchopleural fistula (BPF) with prolonged air leak (PAL) is most often, though not always, a sequela of lung resection. When this complication occurs post-operatively, it is associated with substantial morbidity and mortality. Surgical closure of the defect is considered the definitive approach to controlling the source of the leak, but many patients with this condition are suboptimal operative candidates. Therefore there has been active interest for decades in the development of effective endoscopic management options. Successful use of numerous bronchoscopic techniques has been reported in the literature largely in the form of retrospective series and, at best, small prospective trials. …

Hyperfiltration-Associated Biomechanical Forces In Glomerular Injury And Response: Potential Role For Eicosanoids., Mukut Sharma, Ram Sharma, Ellen T. Mccarthy, Virginia J. Savin, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Hyperfiltration is a well-known risk factor in progressive loss of renal function in chronic kidney disease (CKD) secondary to various diseases. A reduced number of functional nephrons due to congenital or acquired cause(s) results in hyperfiltration in the remnant kidney. Hyperfiltration-associated increase in biomechanical forces, namely pressure-induced tensile stress and fluid flow-induced shear stress (FFSS) determine cellular injury and response. We believe the current treatment of CKD yields limited success because it largely attenuates pressure-induced tensile stress changes but not the effect of FFSS on podocytes. Studies on glomerular podocytes, tubular epithelial cells and bone osteocytes provide evidence for a …

Efficacy And Safety Of Methylprednisolone Sodium Succinate In Acute Spinal Cord Injury: A Systematic Review, Michael G. Fehlings, Jefferson R. Wilson, James S. Harrop, Brian Kwon, Lindsay A. Tetreault, Paul M. Arnold, Jeffrey M. Singh, Gregory W.J. Hawryluk, Joseph R. Dettori

Department of Neurosurgery Faculty Papers

Study Design: Systematic review and meta-analysis. Objective: The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI). Methods: A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies were critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated …

Intracranial Eeg Fluctuates Over Months After Implanting Electrodes In Human Brain., Hoameng Ung, Steven N. Baldassano, Hank Bink, Abba M. Krieger, Shawniqua Williams, Flavia Vitale, Chengyuan Wu, Dean Freestone, Ewan Nurse, Kent Leyde, Kathryn A. Davis, Mark Cook, Brian Litt

Department of Neurosurgery Faculty Papers

OBJECTIVE: Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings.

APPROACH: Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for …

The Rna-Binding Protein Hur Contributes To Neuroinflammation By Promoting C-C Chemokine Receptor 6 (Ccr6) Expression On Th17 Cells., Jing Chen, Jennifer L. Martindale, Carole Cramer, Myriam Gorospe, Ulus Atasoy, Paul D. Drew, Shiguang Yu

Department of Neurology Faculty Papers

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA …

Readiness For Antimicrobial Resistance (Amr) Surveillance In Pakistan; A Model For Laboratory Strengthening, Dania Khalid Saeed, Rumina Hasan, Mahwish Naim, Afia Zafar, Erum Khan, Kauser Jabeen, Seema Irfan, Imran Ahmed Haq, Mohammad Zeeshan, Zabin Wajidali, Joveria Farooqi, Sadia Shakoor, Abdul Chagla, Jason Rao

Department of Pathology and Laboratory Medicine

Background: Limited capacity of laboratories for antimicrobial susceptibility testing (AST) presents a critical diagnostic bottleneck in resource limited countries. This paper aims to identify such gaps and to explore whether laboratory networks could contribute towards improving AST in low resource settings.
Methods: A self-assessment tool to assess antimicrobial susceptibility testing capacity was administered as a pre-workshop activity to participants from 30 microbiology laboratories in 3 cities in Pakistan. Data from public and private laboratories was analyzed and capacity of each scored in percentage terms. Laboratories from Karachi were invited to join a support network. A cohort of five laboratories that …

Readiness For Antimicrobial Resistance (Amr) Surveillance In Pakistan; A Model For Laboratory Strengthening, Dania Khalid Saeed, Rumina Hasan, Mahwish Naim, Afia Zafar, Erum Khan, Kauser Jabeen, Seema Irfan, Imran Ahmed Haq, Mohammad Zeeshan, Zabin Wajidali, Joveria Farooqi, Sadia Shakoor, Abdul Chagla, Jason Rao

Department of Pathology and Laboratory Medicine

Background: Limited capacity of laboratories for antimicrobial susceptibility testing (AST) presents a critical diagnostic bottleneck in resource limited countries. This paper aims to identify such gaps and to explore whether laboratory networks could contribute towards improving AST in low resource settings.
Methods: A self-assessment tool to assess antimicrobial susceptibility testing capacity was administered as a pre-workshop activity to participants from 30 microbiology laboratories in 3 cities in Pakistan. Data from public and private laboratories was analyzed and capacity of each scored in percentage terms. Laboratories from Karachi were invited to join a support network. A cohort of five laboratories that …

The Role Of Oral Vitamin D In Several Skin Diseases, Astri Adelia, Larisa Paramitha Wibawa, Adhimukti T. Sampurna, Windy K. Budianti, Farida Zubier

Journal of General - Procedural Dermatology and Venereology Indonesia

Vitamin D has many benefits for body and skin health. One of them is to regulate the immune system, both cellular and humoral. The pathogenesis of many skin diseases is associated with disturbance in regulation of cellular immune system. Research on the relationship between blood level of vitamin D and several diseases in dermatology is currently very advanced. Oral vitamin D is known to have many functions that play a role in the pathogenesis of several diseases of the skin. Therefore, its current use as a primary or supplemental therapy has been widely studied. Knowledge on various skin diseases with …

Debate On Human Aging And Lifespan, Mohammad Rafi, Abass Alavi

Department of Neurology Faculty Papers

The issue of human lifespan has long been a matter of controversy among scientists. In spite of the recent claim by Dong et al that human lifespan is limited to 115 years, with the mounting improvements in biotechnology and scientific understanding of aging, we may be confident that aging will slow down over the course of the current century extending human longevity much longer than 115 years.

A New Opportunity For Memri, Ryan Cloyd, Moriel H. Vandsburger, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

The Farnesoid X Receptor Negatively Regulates Osteoclastogenesis In Bone Remodeling And Pathological Bone Loss, Ting Zheng, Ju-Hee Kang, Jung-Sun Sim, Jung-Woo Kim, Jeong-Tae Koh, Chan Soo Shin, Hyungsik Lim, Mijung Yim

Publications and Research

Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Since the role of FXR in osteoclast differentiation remains ill-defined, we investigated the biological function of FXR on osteoclastogenesis, using FXR-deficient mice. We demonstrated that FXR deficiency increases osteoclast formation in vitro and in vivo. First, FXR deficiency was found to accelerate osteoclast formation via down-regulation of c-Jun N-terminal kinase (JNK) 1/2 expression. Increased expression of peroxisome proliferator-activated receptor (PPAR)γ and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC- 1)β seems to mediate the pro-osteoclastogenic effect of FXR deficiency via the JNK pathway. In …

The Effects Of Perinatal Oxycodone Exposure On Behavioral Outcome In A Rodent Model, Thitinart Sithisarn, Sandra J. Legan, Philip M. Westgate, Melinda E. Wilson, Kristen Wellmann, Henrietta S. Bada, Susan Barron

Pediatrics Faculty Publications

Opiate addiction is now a major public health problem. Perinatal insults and exposure to opiates such as morphine in utero are well known to affect development of the hypothalamic–pituitary–adrenal axis of the offspring adversely and are associated with a higher risk of developing neurobehavioral problems. Oxycodone is now one of the most frequently abused pain killers during pregnancy; however, limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters neurobehavioral outcomes of the offspring. We demonstrated that exposure to 0.5 mg/kg/day oxycodone in utero was associated with hyperactivity in adult rats in an open field. No significant …

Oxidative Stress-Induced Jnk/Ap-1 Signaling Is A Major Pathway Involved In Selective Apoptosis Of Myelodysplastic Syndrome Cells By Withaferin-A, Karine Z. Oben, Sara S. Alhakeem, Mary Kathryn Mckenna, Jason A. Brandon, Rajeswaran Mani, Sunil K. Noothi, Jinpeng Liu, Shailaja Akunuru, Sanjit Kumar Dhar, Inder P. Singh, Ying Liang, Chi Wang, Ahmed Abdel-Latif, Harold F. Stills Jr., Daret K. St Clair, Hartmut Geiger, Natarajan Muthusamy, Kaoru Tohyama, Ramesh C. Gupta, Subbarao Bondada

Markey Cancer Center Faculty Publications

Myelodysplastic syndromes (MDS) are a diverse group of malignant clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplastic cell morphology in one or more hematopoietic lineages, and a risk of progression to acute myeloid leukemia (AML). Approximately 50% of MDS patients respond to current FDA-approved drug therapies but a majority of responders relapse within 2-3 years. There is therefore a compelling need to identify potential new therapies for MDS treatment. We utilized the MDS-L cell line to investigate the anticancer potential and mechanisms of action of a plant-derived compound, Withaferin A (WFA), in MDS. WFA was potently cytotoxic to …

Anterior Inferior Cerebellar Arteries Juxtaposed With The Internal Acoustic Meatus And Their Relationship To The Cranial Nerve Vii/Viii Complex., Fernando Alonso, Mohammad W Kassem, Joe Iwanaga, Rod J Oskouian, Marios Loukas, Amin Demerdash, R Shane Tubbs

Articles, Abstracts, and Reports

Vascular loops in the cerebellopontine angle (CPA) and their relationship to cranial nerves have been used to explain neurological symptoms. The anterior inferior cerebellar artery (AICA) has variable branches producing vascular loops that can compress the facial cranial nerve (CN) VII and vestibulocochlear (CN VIII) nerves. AICA compression of the facial-vestibulocochlear nerve complex can lead to various clinical presentations, including hemifacial spasm (HFS), tinnitus, and hemiataxia. The formation of arterial loops inside or outside of the internal auditory meatus (IAM) can cause abutment or compression of CN VII and CN VIII. Twenty-five (50 sides) fresh adult cadavers underwent dissection of …

Coding Of Velocity Storage In The Vestibular Nuclei, Sergei B. Yakushin, Theodore Raphan, Bernard Cohen

Publications and Research

Semicircular canal afferents sense angular acceleration and output angular velocity with a short time constant of ≈4.5 s. This output is prolonged by a central integrative network, velocity storage that lengthens the time constants of eye velocity. This mechanism utilizes canal, otolith, and visual (optokinetic) information to align the axis of eye velocity toward the spatial vertical when head orientation is off-vertical axis. Previous studies indicated that vestibular-only (VO) and vestibular-pause-saccade (VPS) neurons located in the medial and superior vestibular nucleus could code all aspects of velocity storage. A recently developed technique enabled prolonged recording while animals were rotated and …

Microstructural Alterations And Oligodendrocyte Dysmaturation In White Matter After Cardiopulmonary Bypass In A Juvenile Porcine Model., Gary R Stinnett, Stephen Lin, Alexandru V Korotcov, Ludmila Korotcova, Paul D Morton, Shruti D Ramachandra, Angeline Pham, Sonali Kumar, Kota Agematsu, David Zurakowski, Paul C Wang, Richard A Jonas, Nobuyuki Ishibashi

Surgery Faculty Publications

BACKGROUND: Newly developed white matter (WM) injury is common after cardiopulmonary bypass (CPB) in severe/complex congenital heart disease. Fractional anisotropy (FA) allows measurement of macroscopic organization of WM pathology but has rarely been applied after CPB. The aims of our animal study were to define CPB-induced FA alterations and to determine correlations between these changes and cellular events after congenital heart disease surgery.

METHODS AND RESULTS: Normal porcine WM development was first assessed between 3 and 7 weeks of age: 3-week-old piglets were randomly assigned to 1 of 3 CPB-induced insults. FA was analyzed in 31 WM structures. WM oligodendrocytes, …

Pharmacologic Or Genetic Targeting Of Glutamine Synthetase Skews Macrophages Toward An M1-Like Phenotype And Inhibits Tumor Metastasis., Erika M. Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, D Craig Hooper, Wouter H. Lamers, Bart Ghesquière, Daniel W. Mcvicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna

Department of Cancer Biology Faculty Papers

Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial …

Chiari I Malformation And Spinal Cord Ischemia In A Cadaver., Faizullah Mashriqi, Marios Loukas, Rod J Oskouian, Anthony V D'Antoni, R Shane Tubbs

Articles, Abstracts, and Reports

With advanced imaging, the Chiari I malformation (CIM) is more frequently diagnosed than in the past when this entity was identified most commonly at autopsy. Herein, we report the rare case of an adult cadaver found not only to have CIM but also adjacent spinal cord ischemia. This case is discussed in the context of chronic compression of the spinal cord by a CIM and the need for close monitoring of these patients.

Posttranscriptional Upregulation Of Idh1 By Hur Establishes A Powerful Survival Phenotype In Pancreatic Cancer Cells., Mahsa Zarei, Shruti Lal, Seth J. Parker, Avinoam Nevler, Ali Vaziri-Gohar, Katerina Dukleska, Nicole C. Mambelli-Lisboa, Cynthia Moffat, Fernando F Blanco, Saswati N. Chand, Masaya Jimbo, Joseph A. Cozzitorto, Wei Jiang, Charles J. Yeo, Eric R. Londin, Erin L. Seifert, Christian M. Metallo, Jonathan R. Brody, Jordan M. Winter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C > 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal …