“Feasibility and safety of focused ultrasound-enabled liquid biopsy in the brain of a porcine model” (2020) Scientific Reports
Feasibility and safety of focused ultrasound-enabled liquid biopsy in the brain of a porcine model
(2020) Scientific Reports, 10 (1), art. no. 7449, .
Pacia, C.P.a , Zhu, L.a , Yang, Y.a , Yue, Y.a , Nazeri, A.b , Michael Gach, H.a b c , Talcott, M.R.d , Leuthardt, E.C.a e f g , Chen, H.a c
a Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
c Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO 63108, United States
d Division of Comparative Medicine, Washington University School of Medicine, Saint Louis, MO 63110, United States
e Department of Neurosurgery, Washington University School of Medicine, Saint Louis, MO 63110, United States
f Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO 63110, United States
g Center for Innovation in Neuroscience and Technology, Washington University School of Medicine, Saint Louis, MO 63110, United States
Abstract
Although blood-based liquid biopsy is a promising noninvasive technique to acquire a comprehensive molecular tumor profile by detecting cancer-specific biomarkers (e.g. DNA, RNA, and proteins), there has been limited progress for brain tumor application partially because the low permeability of the blood-brain barrier (BBB) hinders the release of tumor biomarkers. We previously demonstrated focused ultrasound-enabled liquid biopsy (FUS-LBx) that uses FUS to increase BBB permeability in murine glioblastoma models and thus enhance the release of tumor-specific biomarkers into the bloodstream. The objective of this study was to evaluate the feasibility and safety of FUS-LBx in the normal brain tissue of a porcine model. Increased BBB permeability was confirmed by the significant increase (p = 0.0053) in Ktrans (the transfer coefficient from blood to brain extravascular extracellular space) when comparing the FUS-sonicated brain area with the contralateral non-sonicated area. Meanwhile, there was a significant increase in the blood concentrations of glial fibrillary acidic protein (GFAP, p = 0.0074) and myelin basic protein (MBP, p = 0.0039) after FUS sonication as compared with before FUS. There was no detectable tissue damage by T2 *-weighted MRI and histological analysis. Findings from this study suggest that FUS-LBx is a promising technique for noninvasive and localized diagnosis of the molecular profiles of brain diseases with the potential to translate to the clinic. © 2020, The Author(s).
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Paralysis Caused by Spinal Cord Injury After Posterior Fossa Surgery: A Systematic Review” (2020) World Neurosurgery
Paralysis Caused by Spinal Cord Injury After Posterior Fossa Surgery: A Systematic Review
(2020) World Neurosurgery, 139, pp. 151-157.
Yahanda, A.T., Chicoine, M.R.
Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
Abstract
Objective: Paralysis (paraplegia or quadriplegia) after posterior fossa surgery is a rare but devastating complication. We investigated previous reports of this complication to examine similarities among patients, risk factors, and methods by which it may be prevented. Methods: A systematic review was completed according to PRISMA guidelines. Electronic databases were searched until November 2019 using keywords “paraplegia,” “quadriplegia,” or “spinal cord injury” added to “posterior fossa surgery.” Results: Thirteen case reports published between 1996 and 2019 were included. Five (38.5%) involved quadriplegia/quadriparesis and 8 (61.5%) involved paraplegia after surgery. Ten cases (76.9%) were tumor resections and 3 (23.1%) were posterior fossa decompressions (2 for Chiari malformations and 1 for Morquio syndrome). Seven surgeries (53.8%) were performed in the sitting position and 6 (46.2%) were prone. Proposed mechanisms of paralysis involved cervical hyperflexion yielding spinal cord ischemia in 8 patients (61.5%), arterial hypotension in 2 patients (15.4%), spinal cord compression from hematoma in 1 patient (7.7%), and decreased cardiac output in 1 patient (7.7%) (1 study did not propose a cause). Cervical hyperflexion was equally likely in the sitting and prone positions (4 patients each). Only 3 patients (23.1%) involved intraoperative complications (all cardiopulmonary in nature). Conclusions: Paralysis after posterior fossa surgery often involves spinal cord infarction apparently caused by cervical hyperflexion. Extreme care during patient positioning is needed in both the sitting or prone positions. Electrophysiologic monitoring might enable early identification of spinal cord dysfunction to minimize or avoid this complication. © 2020 Elsevier Inc.
Author Keywords
Paralysis; Paraplegia; Posterior fossa surgery; Quadriplegia; Spinal cord injury
Document Type: Review
Publication Stage: Final
Source: Scopus
“Single-cell RNA-seq analysis of human CSF microglia and myeloid cells in neuroinflammation” (2020) Neurology(R) Neuroimmunology & Neuroinflammation
Single-cell RNA-seq analysis of human CSF microglia and myeloid cells in neuroinflammation
(2020) Neurology(R) Neuroimmunology & Neuroinflammation, 7 (4), .
Esaulova, E.a , Cantoni, C.a , Shchukina, I.a , Zaitsev, K.a , Bucelli, R.C.a , Wu, G.F.b , Artyomov, M.N.a , Cross, A.H.a , Edelson, B.T.b
a From the Department of Pathology and Immunology (E.E., I.S., K.Z., G.F.W., M.N.A., B.T.E.) and Department of Neurology (C.C., R.C.B., G.F.W., A.H.C.), Washington University School of Medicine, St. Louis, MO; and Computer Technologies Department (K.Z.), ITMO University, St. Petersburg, Russia
b From the Department of Pathology and Immunology (E.E., I.S., K.Z., G.F.W., M.N.A., B.T.E.) and Department of Neurology (C.C., R.C.B., G.F.W., A.H.C.), Washington University School of Medicine, St. Louis, MO; and Computer Technologies Department (K.Z.), ITMO University, St. Petersburg, Russia. wug@neuro.wustl.edu
Abstract
OBJECTIVE: To identify and characterize myeloid cell populations within the CSF of patients with MS and anti-myelin oligodendrocyte glycoprotein (MOG) disorder by high-resolution single-cell gene expression analysis. METHODS: Single-cell RNA sequencing (scRNA-seq) was used to profile individual cells of CSF and blood from 2 subjects with relapsing-remitting MS (RRMS) and one with anti-MOG disorder. Publicly available scRNA-seq data from the blood and CSF of 2 subjects with HIV were also analyzed. An informatics pipeline was used to cluster cell populations by transcriptomic profiling. Based on gene expression by CSF myeloid cells, a flow cytometry panel was devised to examine myeloid cell populations from the CSF of 11 additional subjects, including individuals with RRMS, anti-MOG disorder, and control subjects without inflammatory demyelination. RESULTS: Common myeloid populations were identified within the CSF of subjects with RRMS, anti-MOG disorder, and HIV. These included monocytes, conventional and plasmacytoid dendritic cells, and cells with a transcriptomic signature matching microglia. Microglia could be discriminated from other myeloid cell populations in the CSF by flow cytometry. CONCLUSIONS: High-resolution single-cell gene expression analysis clearly distinguishes distinct myeloid cell types present within the CSF of subjects with neuroinflammation. A population of microglia exists within the human CSF, which is detectable by surface protein expression. The function of these cells during immunity and disease requires further investigation. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism” (2020) Molecular Metabolism
Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism
(2020) Molecular Metabolism, 37, art. no. 100989, .
Held, N.M.a , Wefers, J.b , van Weeghel, M.a c , Daemen, S.d , Hansen, J.b , Vaz, F.M.a c , van Moorsel, D.b , Hesselink, M.K.C.b , Houtkooper, R.H.a , Schrauwen, P.b
a Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, 1105 AZ, Netherlands
b Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, P.O. Box 616, Maastricht, 6200 MD, Netherlands
c Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, Netherlands
d Diabetes Research Center, Washington University, St. Louis, MO 63110, United States
Abstract
Objective: Human energy metabolism is under the regulation of the molecular circadian clock; we recently reported that mitochondrial respiration displays a day-night rhythm under study conditions that are similar to real life. Mitochondria are interconnected with lipid droplets, which are of importance in fuel utilization and play a role in muscle insulin sensitivity. Here, we investigated if skeletal muscle lipid content and composition also display day-night rhythmicity in healthy, lean volunteers. Methods: Skeletal muscle biopsies were obtained from 12 healthy lean male volunteers every 5 h over a 24 h period. Volunteers were provided with standardized meals, and biopsies were taken 4.5 h after each last meal. Lipid droplet size and number were investigated by confocal microscopy. Additionally, the muscle lipidome was assessed using UPLC/HRMS-based semi-targeted lipidomics. Results: Confocal microscopy revealed diurnal differences in intramyocellular lipid content (P < 0.05) and lipid droplet size in oxidative type 1 muscle fibers (P < 0.01). Lipidomics analysis revealed that 13% of all detected lipids displayed significant day-night rhythmicity. The most rhythmic lipid species were glycerophospholipids and diacylglycerols (DAG), with the latter being the largest fraction (>50% of all rhythmic species). DAG levels showed a day-night pattern with a trough at 1 PM and a peak at 4 AM. Conclusions: Using two distinct methods, our findings show that myocellular lipid content and whole muscle lipid composition vary across the day-night cycle under normal living conditions. In particular, day-night rhythmicity was present in over half of the DAG lipid species. Future studies are needed to investigate whether rhythmicity in DAG is functionally related to insulin sensitivity and how this might be altered in prediabetes. © 2020 The Authors
Author Keywords
Circadian clock; Human skeletal muscle; Lipid metabolism; Lipidomics
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Update on T cells in the virally infected brain: friends and foes” (2020) Current Opinion in Neurology
Update on T cells in the virally infected brain: friends and foes
(2020) Current Opinion in Neurology, 33 (3), pp. 405-412.
Ai, S.a , Klein, R.S.a b c
a Departments of Medicine
b Pathology and Immunology
c Neurosciences Washington University School of Medicine, St. Louis, MO, United States
Abstract
PURPOSE OF REVIEW: The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated. RECENT FINDINGS: The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including resident memory T cells (Trm), in antiviral immunity and, unexpectedly, in postinfectious cognitive dysfunction. Mechanisms of T-cell-mediated effects include differential innate immune signaling within neural cells that are virus-specific. SUMMARY: T-cell cytokines that are essential for cell-mediated virologic control during neurotropic viral infections have recently been identified as potential targets to prevent post-infection memory disorders. Further identification of T-cell subsets, their antigen specificity, and postinfection localization of Trm will enhance the efficacy of immunotherapies through minimization of immunopathology.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Corrigendum to: Local Perturbations of Cortical Excitability Propagate Differentially Through Large-Scale Functional Networks” (2020) Cerebral Cortex (New York, N.Y. : 1991)
Corrigendum to: Local Perturbations of Cortical Excitability Propagate Differentially Through Large-Scale Functional Networks
(2020) Cerebral Cortex (New York, N.Y. : 1991), 30 (5), p. 3431.
Rosenthal, Z.P.a b c , Raut, R.V.b d , Yan, P.c , Koko, D.c , Kraft, A.W.e , Czerniewski, L.c f , Acland, B.b g , Mitra, A.a b d , Snyder, L.H.f g , Bauer, A.Q.d f , Snyder, A.Z.c d , Culver, J.P.d f h , Raichle, M.E.c d f g , Lee, J.-M.c d f
a Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, 63110, USA
b Graduate Program of Neuroscience, Washington University School of Medicine, St. Louis, MO, 63110, USA
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110, USA
d Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA
e Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, MA, Boston, 02115, United States
f Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, 63110, USA
g Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, 63110, USA
h Department of Physics, Washington University School of Medicine, St. Louis, MO, 63110, USA
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Corrigendum: Joint Attention and Brain Functional Connectivity in Infants and Toddlers” (2020) Cerebral Cortex (New York, N.Y. : 1991)
Corrigendum: Joint Attention and Brain Functional Connectivity in Infants and Toddlers
(2020) Cerebral Cortex (New York, N.Y. : 1991), 30 (5), pp. 3433-3434.
Eggebrecht, A.T.a , Elison, J.T.b , Feczko, E.c , Todorov, A.d , Wolff, J.J.e , Kandala, S.d , Adams, C.M.d , Snyder, A.Z.a , Lewis, J.D.f , Estes, A.M.g , Zwaigenbaum, L.h , Botteron, K.N.a d , McKinstry, R.C.a , Constantino, J.N.d , Evans, A.f , Hazlett, H.C.i , Dager, S.j , Paterson, S.J.k l , Schultz, R.T.k , Styner, M.A.i , Gerig, G.m , Das, S.f , Kostopoulos, P.f , Schlaggar, B.L.n , Petersen, S.E.n , Piven, J.i , Pruett, J.R.d , IBIS Networko
a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA
b Institute of Child Development, University of Minnesota, Minneapolis, United States
c Department of Behavioral Neuroscience, Oregon Health & SciencesPortland OR 97239, United States
d Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA
e Department of Educational Psychology, University of Minnesota, Minneapolis, United States
f McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada
g Department of Speech and Hearing Sciences, University of Washington, Seattle, WA 98195, USA
h Department of Psychiatry, University of Alberta, 1E1 Walter Mackenzie Health Sciences Centre (WMC), Edmonton, AB T6G 2B7, Canada
i Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States
j Department of Radiology, University of Washington, Seattle, WA 98195, USA
k Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, United States
l Department of Psychology, Temple University, Philadelphia, PA 19122, United States
m Tandon School of Engineering, New York University, Brooklyn, NY 11201, USA
n Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“A clinical trial of isradipine: What went wrong?” (2020) Annals of Internal Medicine
A clinical trial of isradipine: What went wrong?
(2020) Annals of Internal Medicine, 172 (9), pp. 625-626.
Maiti, B.a b , Perlmutter, J.S.a b
a Washington University School of Medicine, St. Louis, MO, United States
b Washington University School of Medicine, Campus Box 8111, 660 South Euclid Avenue, Saint Louis, MO 63110, United States
Document Type: Editorial
Publication Stage: Final
Source: Scopus
“Unmasking Intra-tumoral Heterogeneity and Clonal Evolution in NF1-MPNST” (2020) Genes
Unmasking Intra-tumoral Heterogeneity and Clonal Evolution in NF1-MPNST
(2020) Genes, 11 (5), .
Moon, C.-I.a , Tompkins, W.b , Wang, Y.a , Godec, A.c , Zhang, X.a , Pipkorn, P.d e , Miller, C.A.e f , Dehner, C.g , Dahiya, S.e g , Hirbe, A.C.a e
a Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
b Washington University School of Medicine, St. Louis, MO 63110, USA
c College of Human Medicine, Michigan State University, East Lansing, United States
d Department of Otolaryngology, Division of Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
e Siteman Cancer Center, St. Louis, MO 63110, USA
f McDonnell Genome Institute, Division of Oncology-Stem Cell Biology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
g Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Abstract
Sarcomas are highly aggressive cancers that have a high propensity for metastasis, fail to respond to conventional therapies, and carry a poor 5-year survival rate. This is particularly true for patients with neurofibromatosis type 1 (NF1), in which 8%-13% of affected individuals will develop a malignant peripheral nerve sheath tumor (MPNST). Despite continued research, no effective therapies have emerged from recent clinical trials based on preclinical work. One explanation for these failures could be the lack of attention to intra-tumoral heterogeneity. Prior studies have relied on a single sample from these tumors, which may not be representative of all subclones present within the tumor. In the current study, samples were taken from three distinct areas within a single tumor from a patient with an NF1-MPNST. Whole exome sequencing, RNA sequencing, and copy number analysis were performed on each sample. A blood sample was obtained as a germline DNA control. Distinct mutational signatures were identified in different areas of the tumor as well as significant differences in gene expression among the spatially distinct areas, leading to an understanding of the clonal evolution within this patient. These data suggest that multi-regional sampling may be important for driver gene identification and biomarker development in the future.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“The histone deacetylase complex midac regulates a neurodevelopmental gene expression program to control neurite outgrowth” (2020) eLife
The histone deacetylase complex midac regulates a neurodevelopmental gene expression program to control neurite outgrowth
(2020) eLife, 9, art. no. e57519, .
Mondal, B.a , Jin, H.b , Kallappagoudar, S.a , Sedkov, Y.a , Martinez, T.a , Sentmanat, M.F.c , Poet, G.J.d e , Li, C.d , Fan, Y.b , Pruett-Miller, S.M.a , Herz, H.-M.a
a Department of Cell & Molecular Biology, St. Jude Children’s Research Hospital, Memphis, United States
b Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, United States
c Genome Engineering & iPS Center, Department of Genetics, Washington University, St. Louis, United States
d Department of Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, United States
e The Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, United Kingdom
Abstract
The mitotic deacetylase complex (MiDAC) is a recently identified histone deacetylase (HDAC) complex. While other HDAC complexes have been implicated in neurogenesis, the physiological role of MiDAC remains unknown. Here, we show that MiDAC constitutes an important regulator of neural differentiation. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC upregulates gene expression of pro-neural genes such as those encoding the secreted ligands SLIT3 and NETRIN1 (NTN1) by a mechanism suggestive of H4K20ac removal on promoters and enhancers. Conversely, MiDAC inhibits gene expression by reducing H3K27ac on promoter-proximal and-distal elements of negative regulators of neurogenesis. Furthermore, loss of MiDAC results in neurite outgrowth defects that can be rescued by supplementation with SLIT3 and/or NTN1. These findings indicate a crucial role for MiDAC in regulating the ligands of the SLIT3 and NTN1 signaling axes to ensure the proper integrity of neurite development. © Mondal et al.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Reinforcement biases subsequent perceptual decisions when confidence is low: A widespread behavioral phenomenon” (2020) eLife
Reinforcement biases subsequent perceptual decisions when confidence is low: A widespread behavioral phenomenon
(2020) eLife, 9, art. no. e49834, .
Lak, A.a b , Hueske, E.c d e , Hirokawa, J.f g , Masset, P.c f h , Ott, T.f i , Urai, A.E.f j , Donner, T.H.j , Carandini, M.b , Tonegawa, S.d k , Uchida, N.c , Kepecs, A.f i
a Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, United Kingdom
b UCL Institute of Ophthalmology, University College London, London, WC1E 6BT, United Kingdom
c Department of Molecular and Cellular Biology & Center for Brain Science, Harvard University, Cambridge, MA 02138, United States
d RIKEN-MIT Laboratory, Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, United States
e McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
f Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, United States
g Graduate School of Brain Science, Doshisha University, Kyoto, Kyotanabe, Japan
h Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, United States
i Departments of Neuroscience and Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
j Department of Neurophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany
k Howard Hughes Medical Institute at Massachusetts Institute of Technology, Cambridge, MA, United States
Abstract
Learning from successes and failures often improves the quality of subsequent decisions. Past outcomes, however, should not influence purely perceptual decisions after task acquisition is complete since these are designed so that only sensory evidence determines the correct choice. Yet, numerous studies report that outcomes can bias perceptual decisions, causing spurious changes in choice behavior without improving accuracy. Here we show that the effects of reward on perceptual decisions are principled: past rewards bias future choices specifically when previous choice was difficult and hence decision confidence was low. We identified this phenomenon in six datasets from four laboratories, across mice, rats, and humans, and sensory modalities from olfaction and audition to vision. We show that this choice-updating strategy can be explained by reinforcement learning models incorporating statistical decision confidence into their teaching signals. Thus, despite being suboptimal from the experimenter’s perspective, confidence-guided reinforcement learning optimizes behavior in uncertain, real-world situations. © 2020, eLife Sciences Publications Ltd. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery” (2020) Pituitary
Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery
(2020) Pituitary, .
Hwang, J.Y.a , Aum, D.J.a , Chicoine, M.R.a , Dacey, R.G., Jra , Osbun, J.W.a , Rich, K.M.a , Zipfel, G.J.a , Klatt-Cromwell, C.N.b , McJunkin, J.L.b , Pipkorn, P.b , Schneider, J.S.b , Silverstein, J.M.a c , Kim, A.H.a d e
a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States
c Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO, United States
d Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Purpose: Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. Methods: A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. Results: Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. Conclusions: Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Endocrine status; Endoscopic endonasal surgery; Endoscopic transsphenoidal surgery; Nonfunctioning pituitary adenomas
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“A College First-Year Mindfulness Seminar to Enhance Psychological Well-Being and Cognitive Function” (2020) Journal of Student Affairs Research and Practice
A College First-Year Mindfulness Seminar to Enhance Psychological Well-Being and Cognitive Function
(2020) Journal of Student Affairs Research and Practice, .
Tang, R.a , Broderick, P.b , Bono, T.c , Dvoráková, K.d , Braver, T.a
a Washington University in Saint Louis, United States
b Pennsylvania State University, United States
c Washington University in St. Louis, United States
d Prague’s National Institute for Mental Health, Czech Republic
Abstract
Mindfulness training (MT) has shown promise in improving psychological health among college students yet has rarely been evaluated as an addition to the college academic curriculum. Here, we demonstrate the feasibility and effectiveness of a first-year MT seminar offered to residential students at a selective private university, evaluating its impact on psychological and cognitive functioning in relationship to a comparable positive psychology seminar. The results suggest the potential for first-year programs that promote student well-being. © 2020, © NASPA 2020.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“In Vivo Imaging of Gray Matter Microstructure in Major Psychiatric Disorders: Opportunities for Clinical Translation” (2020) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
In Vivo Imaging of Gray Matter Microstructure in Major Psychiatric Disorders: Opportunities for Clinical Translation
(2020) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, .
Nazeri, A.a , Schifani, C.b , Anderson, J.A.E.b , Ameis, S.H.c d e f , Voineskos, A.N.b e f
a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
b Kimel Family Translational Imaging Genetics Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
c Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
d Centre for Brain and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
e Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
f Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
Abstract
Postmortem studies reveal that individuals with major neuropsychiatric disorders such as schizophrenia and autism spectrum disorder have gray matter microstructural abnormalities. These include abnormalities in neuropil organization, expression of proteins supporting neuritic and synaptic integrity, and myelination. Genetic and postmortem studies suggest that these changes may be causally linked to the pathogenesis of these disorders. Advances in diffusion-weighted magnetic resonance image (dMRI) acquisition techniques and biophysical modeling allow for the quantification of gray matter microstructure in vivo. While several biophysical models for imaging microstructural properties are available, one in particular, neurite orientation dispersion and density imaging (NODDI), holds great promise for clinical applications. NODDI can be applied to both gray and white matter and requires only a single extra shell beyond a standard dMRI acquisition. Since its development only a few years ago, the NODDI algorithm has been used to characterize gray matter microstructure in schizophrenia, Alzheimer’s disease, healthy aging, and development. These investigations have shown that microstructural findings in vivo, using NODDI, align with postmortem findings. Not only do NODDI and other advanced dMRI-based modeling methods provide a window into the brain previously only available postmortem, but they may be more sensitive to certain brain changes than conventional magnetic resonance imaging approaches. This opens up exciting new possibilities for clinicians to more rapidly detect disease signatures and allows earlier intervention in the course of the disease. Given that neurites and gray matter microstructure have the capacity to rapidly remodel, these novel dMRI-based methods represent an opportunity to noninvasively monitor neuroplastic changes posttherapy within much shorter time scales. © 2020 Society of Biological Psychiatry
Author Keywords
Autism spectrum disorder; Diffusion-weighted MRI; Gray matter microstructure; Imaging; NODDI; Schizophrenia
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“White Matter Hyperintensities Related to Parkinson’s Disease Executive Function” (2020) Movement Disorders Clinical Practice
White Matter Hyperintensities Related to Parkinson’s Disease Executive Function
(2020) Movement Disorders Clinical Practice, .
Linortner, P.a , McDaniel, C.a , Shahid, M.a , Levine, T.F.a b , Tian, L.c , Cholerton, B.d , Poston, K.L.a e
a Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, United States
b Psychological & Brain Sciences, Washington University, St. Louis, MO, United States
c Department of Biomedical Data Science, Stanford University, Palo Alto, CA, United States
d Department of Pathology, Stanford University, Palo Alto, CA, United States
e Department of Neurosurgery, Stanford University, Palo Alto, CA, United States
Abstract
Background: People with Parkinson’s disease (PD) can develop multidomain cognitive impairments; however, it is unclear whether different pathologies underlie domain-specific cognitive dysfunction. Objectives: We investigated the contribution of vascular copathology severity and location, as measured by MRI white matter hyperintensities (WMHs), to domain-specific cognitive impairment in PD. Methods: We studied 85 PD (66.6 ± 9.2 years) and 18 control (65.9 ± 6.6) participants. Using the Fazekas scale for rating the severity of WMH, we subdivided PD into 14 PD–WMH+ and 71 PD–WMH–. Participants underwent global, executive, visuospatial, episodic memory, and language testing. We performed nonparametric permutation testing to create WMH probability maps based on PD-WMH group and cognitive test performance. Results: The PD–WMH+ group showed worse global and executive cognitive performance than the PD–WMH– group. On individual tests, the PD–WMH+ group showed worse Montreal Cognitive Assessment (MoCA), Stroop, Symbol Digit Modalities Test (SDMT), and Digit Span scores. WMH probability maps showed that in the PD–WMH+ group, worse Stroop was associated with lesions centered around the corticospinal tract (CST), forceps major, inferior-fronto-occipital fasciculus, and superior longitudinal fasciculus; worse SDMT with lesions around the CST, forceps major, and posterior corona radiata; worse Digit Span with lesions around the posterior corona radiata; and worse MoCA with lesions around the CST. Conclusions: We found that WMH severity was associated with PD executive dysfunction, including worse attention, working memory, and processing speed. Disruption of key white matter tracts in proximity to vascular lesions could contribute to these specific cognitive impairments. Early treatment of vascular disease might mitigate some executive dysfunction in a subset of patients with PD. © 2020 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Author Keywords
cognitive impairment; executive function; lesion probability mapping; Parkinson’s disease; white matter hyperintensities
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Neurological Prognostication in Children After Cardiac Arrest” (2020) Pediatric Neurology
Neurological Prognostication in Children After Cardiac Arrest
(2020) Pediatric Neurology, .
Smith, A.E.a , Friess, S.H.b
a Division of Pediatric Neurology, Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
b Division of Critical Care Medicine, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Early after pediatric cardiac arrest, families and care providers struggle with the uncertainty of long-term neurological prognosis. Cardiac arrest characteristics such as location, intra-arrest factors, and postarrest events have been associated with outcome. We paid particular attention to postarrest modalities that have been shown to predict neurological outcome. These modalities include neurological examination, somatosensory evoked potentials, electroencephalography, and neuroimaging. There is no one modality that accurately predicts neurological prognosis. Thus, a multimodal approach should be undertaken by both neurologists and intensivists to present a clear and consistent message to families. Methods used for the prediction of long-term neurological prognosis need to be specific enough to identify indivuals with a poor outcome. We review the evidence evaluating children with coma, each with various etiologies of cardiac arrest, outcome measures, and timing of follow-up. © 2020 Elsevier Inc.
Author Keywords
EEG; MRI; Outcome; Pediatric cardiac arrest; Prognostication; SEP
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Examining the self-reported advantages and disadvantages of socially networking about body image and eating disorders” (2020) International Journal of Eating Disorders
Examining the self-reported advantages and disadvantages of socially networking about body image and eating disorders
(2020) International Journal of Eating Disorders, .
Cavazos-Rehg, P.A.a , Fitzsimmons-Craft, E.E.a , Krauss, M.J.a , Anako, N.a b , Xu, C.a b , Kasson, E.a , Costello, S.J.a , Wilfley, D.E.a
a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b George Warren Brown School, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Objective: The purpose of this study is to understand the self-reported advantages and disadvantages of socially networking about body image/eating disorders (EDs) and to examine the openness of these participants to online outreach and support for ED symptoms. Method: A cross-sectional online survey was conducted with a sample of N = 598. Eligible participants were ≥15 years old, English-speaking, and U.S. residents who endorsed posting or following thin-ideal/body-image content on social media. Quantitative measures were used to assess online peer support and online interaction preferences, and to identify ED symptoms. Deductive and inductive qualitative approaches were used to analyze open-ended items about the advantages and disadvantages of social networking about thin-ideal content on social media platforms (SMPs). Results: Among those who posted about the thin-ideal on social media, 70% felt that the peer responses were positive and supportive. Participants generally favored online interaction, and a third stated that they would accept support from someone they did not know online (38%). The most common advantages noted for posting/following thin-ideal content on SMPs were motivation/encouragement to engage in a certain behavior, socializing, and information giving/seeking. The most common disadvantages mentioned for posting/following thin-ideal content on SMPs were that the content elicits negative/bad feelings, having to deal with the negative consequences/reactions of others when socially networking about this topic, and that it triggers a desire to engage in ED behaviors. Discussion: With these findings, researchers, health practitioners, and social media administrators can devise ways to reduce harmful consequences of posting/following body-image/ED content on social media. © 2020 Wiley Periodicals, Inc.
Author Keywords
body image; eating disorders; social media
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Commentary on Hartwell et al. (2020): Alcohol use disorder treatment response—where is the variability?” (2020) Addiction
Commentary on Hartwell et al. (2020): Alcohol use disorder treatment response—where is the variability?
(2020) Addiction, .
Agrawal, A., McCutcheon, V.V.
Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
Author Keywords
Alcohol treatment; alcohol use disorder; alcoholics anonymous; naltrexone; OPRM1; polygenic risk score
Document Type: Note
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access