Arts & Sciences Brown School McKelvey School Medicine Weekly Publications

WashU weekly Neuroscience publications

“Training models for implementing evidence-based psychological treatment for college mental health: A cluster randomized trial study protocol” (2018) Contemporary Clinical Trials

Training models for implementing evidence-based psychological treatment for college mental health: A cluster randomized trial study protocol
(2018) Contemporary Clinical Trials, 72, pp. 117-125. 

Wilfley, D.E.a , Fitzsimmons-Craft, E.E.a , Eichen, D.M.b , Van Buren, D.J.a , Welch, R.R.a , Robinson, A.H.c , Jo, B.c , Raghavan, R.d , Proctor, E.K.e , Wilson, G.T.f , Agras, W.S.e

a Department of Psychiatry, Washington University School of Medicine, Mailstop 8134-29-2100, 660 S. Euclid Ave., St. Louis, MO 63110, United States
b Department of Pediatrics, University of California, San Diego, 8950 Villa La Jolla Dr., Suite C-203, San Diego, CA 92037, United States
c Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, 401 Quarry Rd., Stanford, CA 94305, United States
d School of Social Work, Rutgers, The State University of New Jersey, 536 George St., New Brunswick, NJ 08901, United States
e George Warren Brown School of Social Work, Washington University in St. Louis, CB 1196, One Brookings Drive, St. Louis, MO 63130, United States
f Graduate School of Applied and Professional Psychology, Rutgers, The State University of New Jersey, 152 Frelinghuysen Rd., Piscataway, NJ 08854, United States

Abstract
Mental disorders often emerge in adolescence and young adulthood, and these disorders can have lasting effects on students’ health, social functioning, and education. Although evidence-based treatments have been established for many mental disorders, few community therapists use such treatments. What is needed is a practical, economically feasible means of training clinicians to implement evidence-based treatments suitable for widespread use. This cluster randomized trial will randomize 26 college counseling centers to one of two implementation strategies for training counselors to use interpersonal psychotherapy (IPT), an evidence-based treatment for depression and eating disorders: 1) an external expert consultation model comprising a workshop, therapy manual, and expert follow-up consultation (n = 13); or 2) a train-the-trainer model in which a staff member from the counseling center is coached to train other staff members to implement IPT (n = 13). The primary outcome is therapist adherence to IPT, with secondary outcomes of therapist competence in IPT and client outcomes for depression and eating disorders. Therapist and organizational characteristics will be explored as potential moderators and mediators of implementation outcomes. Implementation costs for each of the training methods will also be assessed. The present study involves partnering with college counseling centers to determine the most effective method to implement IPT for depression and eating disorders in these settings. The results of this study will inform future large-scale dissemination of clinical interventions to mental health service providers by providing evidence for the selection of training methods when an agency chooses to adopt new interventions. © 2018 Elsevier Inc.

Author Keywords
College mental health;  Dissemination;  Evidence-based treatment;  Implementation;  Interpersonal psychotherapy;  Training

Document Type: Article
Source: Scopus

“Effects of Cable News Watching on Older Adults’ Physiological and Self-Reported Stress and Cognitive Function” (2018) International Journal of Aging and Human Development

Effects of Cable News Watching on Older Adults’ Physiological and Self-Reported Stress and Cognitive Function
(2018) International Journal of Aging and Human Development, 87 (2), pp. 111-123. 

Deal, C., Bogdan, R., Miller, J.P., Rodebaugh, T., Caburnay, C., Yingling, M., Hershey, T., Schweiger, J., Lenze, E.J.

Washington University, St Louis, MO, United States

Abstract
Older adults are the largest consumer of cable news, which includes negative and politicized content and may constitute a daily stressor. As older adults are also vulnerable to the negative consequences of stress, we hypothesized that cable news watching could induce a stress reaction and impair cognitive function. We tested exposures to cable news (i.e., Fox News and MSNBC) in a within-subject randomized controlled design in 34 healthy older adults. We also included negative (Public Broadcasting Station) and positive (trier social stress test) controls. Cable news watching had no effect on psychological stress, physiological stress, or cognitive function. This remained true even if the news exposures were discordant with participants’ political affiliation. We conclude that brief cable news watching does not induce a physiological or subjective stress response or cognitive impairment among healthy older adults. © The Author(s) 2017.

Author Keywords
aging;  cognition;  cortisol;  memory;  stressors;  television

Document Type: Article
Source: Scopus

“Parcellating Cerebral Cortex: How Invasive Animal Studies Inform Noninvasive Mapmaking in Humans” (2018) Neuron

Parcellating Cerebral Cortex: How Invasive Animal Studies Inform Noninvasive Mapmaking in Humans
(2018) Neuron, 99 (4), pp. 640-663. Cited 1 time.

Van Essen, D.C.a , Glasser, M.F.a b

a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
b St. Luke’s Hospital, St. Louis, MO 63107, United States

Abstract
The cerebral cortex in mammals contains a mosaic of cortical areas that differ in function, architecture, connectivity, and/or topographic organization. A combination of local connectivity (within-area microcircuitry) and long-distance (between-area) connectivity enables each area to perform a unique set of computations. Some areas also have characteristic within-area mesoscale organization, reflecting specialized representations of distinct types of information. Cortical areas interact with one another to form functional networks that mediate behavior, and each area may be a part of multiple, partially overlapping networks. Given their importance to the understanding of brain organization, mapping cortical areas across species is a major objective of systems neuroscience and has been a century-long challenge. Here, we review recent progress in multi-modal mapping of mouse and nonhuman primate cortex, mainly using invasive experimental methods. These studies also provide a neuroanatomical foundation for mapping human cerebral cortex using noninvasive neuroimaging, including a new map of human cortical areas that we generated using a semiautomated analysis of high-quality, multimodal neuroimaging data. We contrast our semiautomated approach to human multimodal cortical mapping with various extant fully automated human brain parcellations that are based on only a single imaging modality and offer suggestions on how to best advance the noninvasive brain parcellation field. We discuss the limitations as well as the strengths of current noninvasive methods of mapping brain function, architecture, connectivity, and topography and of current approaches to mapping the brain’s functional networks. Van Essen and Glasser review recent progress in subdividing the cerebral cortex in mice and monkeys and explain how this work laid the foundation for a new multimodal human cortical map based on magnetic resonance imaging data from the Human Connectome Project. © 2018 Elsevier Inc.

Author Keywords
architectonics;  brain;  connectivity;  cortical areas;  function;  networks;  neuroanatomy;  nonhuman primate;  parcellation;  topography

Document Type: Review
Source: Scopus

“Macrophage angiotensin II type 2 receptor triggers neuropathic pain” (2018) Proceedings of the National Academy of Sciences of the United States of America

Macrophage angiotensin II type 2 receptor triggers neuropathic pain
(2018) Proceedings of the National Academy of Sciences of the United States of America, 115 (34), pp. E8057-E8066. 

Shepherd, A.J.a b , Mickle, A.D.a b , Golden, J.P.a , Mack, M.R.c , Halabi, C.M.d , De Kloet, A.D.e , Samineni, V.K.a , Kim, B.S.c , Krause, E.G.f , Gereau, R.W.a g , Mohapatra, D.P.a b h

a Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
c Center for the Study of Itch, Department of Dermatology, Washington University School of Medicine, St. Louis, MO 63110, United States
d Division of Nephrology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL 32610, United States
f Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610, United States
g Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
h Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Peripheral nerve damage initiates a complex series of structural and cellular processes that culminate in chronic neuropathic pain. The recent success of a type 2 angiotensin II (Ang II) receptor (AT2R) antagonist in a phase II clinical trial for the treatment of postherpetic neuralgia suggests angiotensin signaling is involved in neuropathic pain. However, transcriptome analysis indicates a lack of AT2R gene (Agtr2) expression in human and rodent sensory ganglia, raising questions regarding the tissue/cell target underlying the analgesic effect of AT2R antagonism. We show that selective antagonism of AT2R attenuates neuropathic but not inflammatory mechanical and cold pain hypersensitivity behaviors in mice. Agtr2-expressing macrophages (MΦs) constitute the predominant immune cells that infiltrate the site of nerve injury. Interestingly, neuropathic mechanical and cold pain hypersensitivity can be attenuated by chemogenetic depletion of peripheral MΦs and AT2R-null hematopoietic cell transplantation. Our study identifies AT2R on peripheral MΦs as a critical trigger for pain sensitization at the site of nerve injury, and therefore proposes a translatable peripheral mechanism underlying chronic neuropathic pain. © 2018 National Academy of Sciences. All Rights Reserved.

Author Keywords
Angiotensin;  AT2R;  Chemogenetics;  Macrophage;  Neuropathic pain

Document Type: Article
Source: Scopus

“Outcomes of Patients With Syncope and Suspected Dementia” (2018) Academic Emergency Medicine

Outcomes of Patients With Syncope and Suspected Dementia
(2018) Academic Emergency Medicine, 25 (8), pp. 880-890. 

Holden, T.R.a c , Shah, M.N.b , Gibson, T.A.d , Weiss, R.E.d , Yagapen, A.N.e , Malveau, S.E.e , Adler, D.H.f , Bastani, A.g , Baugh, C.W.h , Caterino, J.M.i , Clark, C.L.j , Diercks, D.B.k , Hollander, J.E.l , Nicks, B.A.m , Nishijima, D.K.n , Stiffler, K.A.o , Storrow, A.B.p , Wilber, S.T.o , Sun, B.C.e

a Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
b Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Biostatistics, Fielding School of Public Health, University of California at Los Angeles, Los Angeles, CA, United States
e Center for Policy and Research in Emergency Medicine, Department of Emergency Medicine, Oregon Heath & Science University, Portland, OR, United States
f Department of Emergency Medicine, University of Rochester, Rochester, NY, United States
g Department of Emergency Medicine, William Beaumont Hospital-Troy, Troy, MI, United States
h Department of Emergency Medicine, Brigham& Women’s Hospital, Boston, MA, United States
i Department of Emergency Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States
j Department of Emergency Medicine, William Beaumont Hospital-Royal Oak, Royal Oak, MI, United States
k Department of Emergency Medicine, University of Texas–Southwestern, Dallas, TX, United States
l Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, United States
m Department of Emergency Medicine, Wake Forest School of Medicine, Winston Salem, NC, United States
n Department of Emergency Medicine, University of California Davis School of Medicine, Sacramento, CA, United States
o Department of Emergency Medicine, Northeast Ohio Medical University, Rootstown, OH, United States
p Department of Emergency Medicine, Vanderbilt University, Nashville, TN, United States

Abstract
Objectives: Syncope and near-syncope are common in patients with dementia and a leading cause of emergency department (ED) evaluation and subsequent hospitalization. The objective of this study was to describe the clinical trajectory and short-term outcomes of patients who presented to the ED with syncope or near-syncope and were assessed by their ED provider to have dementia. Methods: This multisite prospective cohort study included patients 60 years of age or older who presented to the ED with syncope or near-syncope between 2013 and 2016. We analyzed a subcohort of 279 patients who were identified by the treating ED provider to have baseline dementia. We collected comprehensive patient-level, utilization, and outcomes data through interviews, provider surveys, and chart abstraction. Outcome measures included serious conditions related to syncope and death. Results: Overall, 221 patients (79%) were hospitalized with a median length of stay of 2.1 days. A total of 46 patients (16%) were diagnosed with a serious condition in the ED. Of the 179 hospitalized patients who did not have a serious condition identified in the ED, 14 (7.8%) were subsequently diagnosed with a serious condition during the hospitalization, and an additional 12 patients (6.7%) were diagnosed postdischarge within 30 days of the index ED visit. There were seven deaths (2.5%) overall, none of which were cardiac-related. No patients who were discharged from the ED died or had a serious condition in the subsequent 30 days. Conclusions: Patients with perceived dementia who presented to the ED with syncope or near-syncope were frequently hospitalized. The diagnosis of a serious condition was uncommon if not identified during the initial ED assessment. Given the known iatrogenic risks of hospitalization for patients with dementia, future investigation of the impact of goals of care discussions on reducing potentially preventable, futile, or unwanted hospitalizations while improving goal-concordant care is warranted. © 2018 by the Society for Academic Emergency Medicine

Document Type: Article
Source: Scopus

“Development and evolution of cerebral and cerebellar cortex” (2018) Brain, Behavior and Evolution

Development and evolution of cerebral and cerebellar cortex
(2018) Brain, Behavior and Evolution, 91 (3), pp. 158-169. Cited 1 time.

Van Essen, D.C., Donahue, C.J., Glasser, M.F.

Department of Neuroscience, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States

Abstract
Cerebral cortex and cerebellar cortex both vary enormously across species in their size and complexity of convolutions. We discuss the development and evolution of cortical structures in terms of anatomy and functional organization. We propose that the distinctive shapes of cerebral and cerebellar cortex can be explained by relatively few developmental processes, notably including mechanical tension along axons and dendrites. Regarding functional organization, we show how maps of myelin content in cerebral cortex are evolutionarily conserved across primates but differ in the proportion of cortex devoted to sensory, cognitive, and other functions. We summarize recent progress and challenges in (i) parcellating cerebral cortex into a mosaic of distinct areas, (ii) distinguishing cortical areas that correspond across species from those that are present in one species but not another, and (iii) using this information along with surface-based interspecies registration to gain deeper insights into cortical evolution. We also comment on the methodological challenges imposed by the differences in anatomical and functional organization of cerebellar cortex relative to cerebral cortex. © 2018 S. Karger AG, Basel. Copyright: All rights reserved.

Author Keywords
Cerebellum;  Cerebral cortex;  Development;  Evolution;  Human;  Neuroanatomy;  Nonhuman primate;  Parcellation

Document Type: Conference Paper
Source: Scopus

“From fossils to function: Integrative and taxonomically inclusive approaches to vertebrate evolutionary neuroscience” (2018) Brain, Behavior and Evolution

From fossils to function: Integrative and taxonomically inclusive approaches to vertebrate evolutionary neuroscience
(2018) Brain, Behavior and Evolution, 91 (3), pp. 123-124. 

Morhardt, A.C.

Department of Neuroscience, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States

Document Type: Editorial
Source: Scopus

“Schwann cell O-GlcNAcylation promotes peripheral nerve remyelination via attenuation of the AP-1 transcription factor JUN” (2018) Proceedings of the National Academy of Sciences of the United States of America

Schwann cell O-GlcNAcylation promotes peripheral nerve remyelination via attenuation of the AP-1 transcription factor JUN
(2018) Proceedings of the National Academy of Sciences of the United States of America, 115 (31), pp. 8019-8024. 

Kim, S.a , Maynard, J.C.b , Strickland, A.a , Burlingame, A.L.b , Milbrandt, J.a c

a Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, United States
c Hope Center for Neurological Diseases, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Schwann cells (SCs), the glia of the peripheral nervous system, play an essential role in nerve regeneration. Upon nerve injury, SCs are reprogrammed into unique “repair SCs,” and these cells remove degenerating axons/myelin debris, promote axonal regrowth, and ultimately remyelinate regenerating axons. The AP-1 transcription factor JUN is promptly induced in SCs upon nerve injury and potently mediates this injury-induced SC plasticity; however, the regulation of these JUN-dependent SC injury responses is unclear. Previously, we produced mice with a SC-specific deletion of O-GlcNAc transferase (OGT). This enzyme catalyzes O-GlcNAcylation, a posttranslational modification that is influenced by the cellular metabolic state. Mice lacking OGT in SCs develop a progressive demyelinating peripheral neuropathy. Here, we investigated the nerve repair process in OGT-SCKO mutant mice and found that the remyelination of regenerating axons is severely impaired. Gene expression profiling of OGT-SCKO SCs revealed that the JUN-dependent SC injury program was elevated in the absence of injury and failed to shut down at the appropriate time after injury. This aberrant JUN activity results in abnormalities in repair SC function and redifferentiation and prevents the timely remyelination. This aberrant nerve injury response is normalized in OGT-SCKO mice with reduced Jun gene dosage in SCs. Mechanistically, OGT O-GlcNAcylates JUN at multiple sites, which then leads to an attenuation of AP-1 transcriptional activity. Together, these results highlight the metabolic oversight of the nerve injury response via the regulation of JUN activity by O-GlcNAcylation, a pathway that could be important in the neuropathy associated with diabetes and aging. © 2018 National Academy of Sciences. All rights reserved.

Author Keywords
JUN;  Nerve injury;  O-GlcNAcylation;  OGT;  Schwann cells

Document Type: Article
Source: Scopus

“Valuation of knowledge and ignorance in mesolimbic reward circuitry” (2018) Proceedings of the National Academy of Sciences of the United States of America

Valuation of knowledge and ignorance in mesolimbic reward circuitry
(2018) Proceedings of the National Academy of Sciences of the United States of America, 115 (31), pp. E7255-E7264. Cited 1 time.

Charpentier, C.J.a b , Bromberg-Martin, E.S.c d e , Sharot, T.a

a Affective Brain Lab, Department of Experimental Psychology, University College London, London, WC1H 0AP, United Kingdom
b Division of Humanities and Social Sciences, California Institute of Technology, Pasadena, CA 91125, United States
c Department of Neuroscience, Columbia University, New York, NY 10032, United States
d Kavli Institute for Brain Science, Columbia University, New York, NY 10032, United States
e Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, United States

Abstract
The pursuit of knowledge is a basic feature of human nature. However, in domains ranging from health to finance people sometimes choose to remain ignorant. Here, we show that valence is central to the process by which the human brain evaluates the opportunity to gain information, explaining why knowledge may not always be preferred. We reveal that the mesolimbic reward circuitry selectively treats the opportunity to gain knowledge about future favorable outcomes, but not unfavorable outcomes, as if it has positive utility. This neural coding predicts participants’ tendency to choose knowledge about future desirable outcomes more often than undesirable ones, and to choose ignorance about future undesirable outcomes more often than desirable ones. Strikingly, participants are willing to pay both for knowledge and ignorance as a function of the expected valence of knowledge. The orbitofrontal cortex (OFC), however, responds to the opportunity to receive knowledge over ignorance regardless of the valence of the information. Connectivity between the OFC and mesolimbic circuitry could contribute to a general preference for knowledge that is also modulated by valence. Our findings characterize the importance of valence in information seeking and its underlying neural computation. This mechanism could lead to suboptimal behavior, such as when people reject medical screenings or monitor investments more during bull than bear markets. © 2018 National Academy of Sciences. All rights reserved.

Author Keywords
Decision making;  Ignorance;  Information seeking;  Knowledge;  Valence

Document Type: Article
Source: Scopus

“Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells” (2018) eLife

Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells
(2018) eLife, 7, art. no. e33385, . 

Giera, S.a b , Luo, R.a b , Ying, Y.a b c , Ackerman, S.D.d g , Jeong, S.-J.a b e h , Stoveken, H.M.f , Folts, C.J.a b , Welsh, C.A.b , Tall, G.G.f , Stevens, B.b , Monk, K.R.d i , Piao, X.a b

a Division of Newborn Medicine, Department of Medicine, Children’s Hospital and Harvard Medical School, Boston, United States
b Department of Neurology, F. M. Kirby Neurobiology Center, Children’s Hospital and Harvard Medical School, Boston, United States
c Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
d Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States
e Department of Neural Development and Diseases, Korea Brain Research Institute (KBRI), Daegu, South Korea
f Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, United States
g Institute of Neuroscience, University of OregonOR, United States
h Convergence Brain Research Department, Korea Brain Research Institute, Daegu, South Korea
i Vollum Institute, Oregon Health and Science University, Portland, United States

Abstract
In the central nervous system (CNS), myelin formation and repair are regulated by oligodendrocyte (OL) lineage cells, which sense and integrate signals from their environment, including from other glial cells and the extracellular matrix (ECM). The signaling pathways that coordinate this complex communication, however, remain poorly understood. The adhesion G protein-coupled receptor ADGRG1 (also known as GPR56) is an evolutionarily conserved regulator of OL development in humans, mice, and zebrafish, although its activating ligand for OL lineage cells is unknown. Here, we report that microglia-derived transglutaminase-2 (TG2) signals to ADGRG1 on OL precursor cells (OPCs) in the presence of the ECM protein laminin and that TG2/ laminin-dependent activation of ADGRG1 promotes OPC proliferation. Signaling by TG2/laminin to ADGRG1 on OPCs additionally improves remyelination in two murine models of demyelination. These findings identify a novel glia-to-glia signaling pathway that promotes myelin formation and repair, and suggest new strategies to enhance remyelination. © Giera et al.

Document Type: Article
Source: Scopus
Access Type: Open Access

“Cooperative p16 and p21 action protects female astrocytes from transformation” (2018) Acta neuropathologica communications

Cooperative p16 and p21 action protects female astrocytes from transformation
(2018) Acta neuropathologica communications, 6 (1), p. 12. 

Kfoury, N.a , Sun, T.a , Yu, K.b , Rockwell, N.a , Tinkum, K.L.a , Qi, Z.c , Warrington, N.M.a , McDonald, P.d , Roy, A.d e , Weir, S.J.e f , Mohila, C.A.g , Deneen, B.b h i j , Rubin, J.B.a k

a Department of Pediatrics, Washington University School of Medicine, Campus Box 8208 ,660 South Euclid Ave, St Louis, MO 63110, United States
b Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States
c Department of Genetics, Washington University School of Medicine, St Louis, MO, United States
d High Throughput Screening Laboratory, University of Kansas, Lawrence, KS, United States
e University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States
f Institute for Advancing Medical Innovation, University of Kansas Medical Center, Kansas City, KS, United States
g Department of Pathology, Texas Children’s Hospital, Houston, TX, United States
h Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States
i Neurological Research Institute at Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United States
j Program in Developmental Biology, Baylor College of Medicine, Houston, TX, United States
k Department of Neuroscience, Washington University School of Medicine, St Louis, United States

Abstract
Mechanisms underlying sex differences in cancer incidence are not defined but likely involve dimorphism (s) in tumor suppressor function at the cellular and organismal levels. As an example, sexual dimorphism in retinoblastoma protein (Rb) activity was shown to block transformation of female, but not male, murine astrocytes in which neurofibromin and p53 function was abrogated (GBM astrocytes). Correlated sex differences in gene expression in the murine GBM astrocytes were found to be highly concordant with sex differences in gene expression in male and female GBM patients, including in the expression of components of the Rb and p53 pathways. To define the basis of this phenomenon, we examined the functions of the cyclin dependent kinase (CDK) inhibitors, p16, p21 and p27 in murine GBM astrocytes under conditions that promote Rb-dependent growth arrest. We found that upon serum deprivation or etoposide-induced DNA damage, female, but not male GBM astrocytes, respond with increased p16 and p21 activity, and cell cycle arrest. In contrast, male GBM astrocytes continue to proliferate, accumulate chromosomal aberrations, exhibit enhanced clonogenic cell activity and in vivo tumorigenesis; all manifestations of broad sex differences in cell cycle regulation and DNA repair. Differences in tumorigenesis disappeared when female GBM astrocytes are also rendered null for p16 and p21. These data elucidate mechanisms underlying sex differences in cancer incidence and demonstrate sex-specific effects of cytotoxic and targeted therapeutics. This has critical implications for lab and clinical research.

Author Keywords
Cyclin dependent kinase inhibitors;  DNA damage response;  Glioblastoma;  Glioma;  p16;  p21;  Rb;  Sex differences

Document Type: Article
Source: Scopus

“Efficacy outcome measures for pediatric procedural sedation clinical trials: An ACTTION systematic review” (2018) Anesthesia and Analgesia

Efficacy outcome measures for pediatric procedural sedation clinical trials: An ACTTION systematic review
(2018) Anesthesia and Analgesia, 126 (3), pp. 956-967. 

Williams, M.R.a , Nayshtut, M.b , Hoefnagel, A.c , McKeown, A.a , Carlson, D.W.d , Cravero, J.e , Lightdale, J.f , Mason, K.P.e , Wilson, S.g , Turk, D.C.h , Dworkin, R.H.i , Ward, D.S.j k

a Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
b Department of Anesthesiology, Robert Wood Johnson -Saint Barnabas Health System, Livingston, NJ, United States
c Department of Anesthesiology, University of Florida, Jacksonville, FL, United States
d Division of Pediatric Hospital Medicine, Washington University, St. Louis Children’s Hospital, St. Louis, Missouri, United States
e Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, MA, United States
f Department of Pediatrics, University of Massachusetts Medical School, UMass Memorial Children’s Medical Center, Worcester, MA, United States
g Division of Pediatric Dentistry, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
h Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States
i Departments of Anesthesiology, Neurology and Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
j Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642, United States
k Department of Anesthesiology, Tufts School of Medicine, Boston, MA, United States

Abstract
Objective evaluations comparing different techniques and approaches to pediatric procedural sedation studies have been limited by a lack of consistency among the outcome measures used in assessment. This study reviewed those existing measures, which have undergone psychometric analysis in a pediatric procedural sedation setting, to determine to what extent and in what circumstances their use is justified across the spectrum of procedures, age groups, and techniques. The results of our study suggest that a wide range of measures has been used to assess the efficacy and effectiveness of pediatric procedural sedation. Most lack the evidence of validity and reliability that is necessary to facilitate rigorous clinical trial design, as well as the evaluation of new drugs and devices. A set of core pediatric sedation outcome domains and outcome measures can be developed on the basis of our findings. We believe that consensus among all stakeholders regarding appropriate domains and measures to evaluate pediatric procedural sedation is possible and that widespread implementation of such recommendations should be pursued. Copyright © 2017 International Anesthesia Research Society.

Document Type: Review
Source: Scopus

“Mental Health, Sleep and Physical Function in Treatment Seeking Women with Urinary Incontinence” (2018) Journal of Urology

Mental Health, Sleep and Physical Function in Treatment Seeking Women with Urinary Incontinence
(2018) Journal of Urology, . Article in Press. 

Siddiqui, N.Y.a , Wiseman, J.B.b , Cella, D.d , Bradley, C.S.f , Lai, H.H.g , Helmuth, M.E.b , Smith, A.R.b , Griffith, J.W.d , Amundsen, C.L.a , Kenton, K.S.e , Clemens, J.Q.c , Kreder, K.J.f , Merion, R.M.b , Kirkali, Z.h , Kusek, J.W.h , Cameron, A.P.c , LURNi

a Division of Urogynecology and Reconstructive Surgery, Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, United States
b Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
c University of Michigan, Ann Arbor, Michigan, United States
d Department of Medical Social Sciences, Northwestern University, Chicago, Illinois, United States
e Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
f Departments of Obstetrics and Gynecology and Urology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States
g Departments of Surgery and Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, United States
h National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States

Abstract
Purpose: We examined how mental health measures, sleep and physical function are associated with the presence and type of urinary incontinence and severity in women seeking treatment for lower urinary tract symptoms. Materials and Methods: This baseline cross-sectional analysis was performed in treatment seeking women with lower urinary tract symptoms. All participants completed the LUTS (Lower Urinary Tract Symptoms) Tool (Pfizer, New York, New York), which was used to classify women based on urinary incontinence symptoms and measure severity. The PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire for depression, anxiety, sleep disturbance and physical function, the PSS (Perceived Stress Scale) and the IPAQ-SF (International Physical Activity Questionnaire Short Form) were administered. Multivariable regression modeling was done to assess associations with urinary symptom presence, type and severity. Results: We studied 510 women with a mean ± SD age of 56 ± 14 years. Of the women 82% were Caucasian, 47% were obese and 14% reported diabetes. Urinary incontinence was reported by 420 women (82.4%), including stress urinary incontinence in 70, urgency urinary incontinence in 85, mixed urinary incontinence in 240 and other urinary incontinence in 25. On adjusted analyses there was no difference in any mental health, sleep or physical function measure based on the presence vs the absence of urinary incontinence. Among women with urinary incontinence PROMIS anxiety and sleep disturbance scores were higher in those with mixed urinary incontinence than stress urinary incontinence. Increasing urinary incontinence severity was associated with higher PROMIS depression and anxiety scores, and higher PSS scores. However, higher urinary incontinence severity was not associated with a difference in sleep or physical function. Conclusions: Among treatment seeking women with lower urinary tract symptoms, increasing urinary incontinence severity rather than the presence or type of urinary incontinence was associated with increased depression, anxiety and stress. © 2018 American Urological Association Education and Research, Inc.

Author Keywords
anxiety;  depression;  patient reported outcome measures;  urinary bladder;  urinary incontinence

Document Type: Article in Press
Source: Scopus

“Breast cancer survivor testimonies: Effects of narrative and emotional valence on affect and cognition” (2018) Cogent Social Sciences

Breast cancer survivor testimonies: Effects of narrative and emotional valence on affect and cognition
(2018) Cogent Social Sciences, 4 (1), art. no. 1426281, . 

Leshner, G.a , Bolls, P.b , Gardner, E.c , Moore, J.a , Kreuter, M.d

a Gaylord College of Journalism & Mass Communication, University of Oklahoma, 3520B Gaylord Hall, 395W. Lindsay, Norman, OK 73019, United States
b College of Media & Communication, Texas Tech University, Lubbock, TX, United States
c University of Missouri, Columbia, MO, United States
d Brown School of Social Work, Washington University, St. Louis, MO, United States

Abstract
This study examined the impact of narrative and emotion on processing of African American breast cancer survivor messages. We employed a two (narrative: present/absent) × three (emotional valence: pleasant/unpleasant/mixed) × four (message repetition) within-subjects experimental design. Findings indicated narrative messages with both pleasant and unpleasant emotional content (mixed) showed the greatest attention (heart rate deceleration) and negative emotional response (corrugator supercillii) while unpleasant narratives showed the least. Surprisingly, non-narrative messages showed the opposite pattern of results, where unpleasant messages showed the greatest attention and emotional response while non-narrative messages with mixed emotional content showed the least. These data initially point to the conclusion that attention for narrative material depends on the valence of emotion expressed in the message, which has both theoretical and practical implications. © 2018, © 2018 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.

Author Keywords
African American;  breast cancer;  cognitive processing;  emotion;  narrative

Document Type: Article
Source: Scopus

“International Issues: A guide to US academic global health programs in neurology” (2018) Neurology

International Issues: A guide to US academic global health programs in neurology
(2018) Neurology, 90 (14), pp. 662-665. 

Samudralwar, R.D.a , Goss, A.b , Rimmer, K.c , Shetler, K.c , Navis, A.d , Siddiqi, O.K.e f g , Chin, J.H.h , Thakur, K.T.c

a Department of Neurology, Washington University, St. Louis, MO, United States
b Department of Neurology, University of California, San Francisco Medical Center, United States
c Department of Neurology, Columbia University Medical Center, New York, NY, United States
d Department of Neurology, Icahn School of Medicine Mount Sinai, New York, NY, United States
e Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
f Center for Virology and Vaccine Research, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
g Department of Internal Medicine, University of Zambia, School of Medicine, Lusaka, Zambia
h Department of Neurology, NYU Langone Health, New York, NY, United States

Document Type: Article
Source: Scopus

“Planning Education for Long-Term Retention: The Cognitive Science and Implementation of Retrieval Practice” (2018) Seminars in Neurology

Planning Education for Long-Term Retention: The Cognitive Science and Implementation of Retrieval Practice
(2018) Seminars in Neurology, 38 (4), pp. 449-456. 

Larsen, D.P.

Department of Neurology, Washington University, School of Medicine, Washington University in St. Louis, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, United States

Abstract
Educational systems are rarely designed for long-term retention of information. Strong evidence has emerged from cognitive psychology and applied education studies that repeated retrieval of information significantly improves retention compared to repeated studying. This effect likely emerges from the processes of memory consolidation and reconsolidation. Consolidation and reconsolidation are the means by which memories are organized into associational networks or schemas that are created and recreated as memories are formed and recalled. As educators implement retrieval practice, they should consider how various test formats lead to different degrees of schema activation. Repeated acts of retrieval provide opportunities for schemas to be updated and strengthened. Spacing of retrieval allows more consolidated schemas to be reactivated. Feedback provides metacognitive monitoring to ensure retrieval accuracy and can lead to shifts from ineffective to effective retrieval strategies. By using the principles of retrieval practice, educators can improve the likelihood that learners will retain information for longer periods of time. © Georg Thieme Verlag KG Stuttgart New York.

Author Keywords
learning;  medical education;  memory;  retrieval practice;  schema;  test-enhanced learning

Document Type: Article
Source: Scopus

“Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: A systematic review and meta-analysis” (2018) Critical Care Medicine

Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: A systematic review and meta-analysis
(2018) Critical Care Medicine, 46 (3), pp. 471-479. 

Stephens, R.J.a , Dettmer, M.R.b , Roberts, B.W.c , Ablordeppey, E.d e , Fowler, S.A.f , Kollef, M.H.g , Fuller, B.M.d e

a Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
b Emergency Services Institute, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH, United States
c Department of Emergency Medicine, Cooper University Hospital, Camden, NJ, United States
d Department of Emergency Medicine, Division of Critical Care, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
e Department of Anesthesiology, Division of Critical Care, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
f Bernard Becker Medical Library, Washington University in St. Louis, St. Louis, MO, United States
g Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States

Abstract
Objectives: Emerging data suggest that early deep sedation may negatively impact clinical outcomes. This systematic review and meta-analysis defines and quantifies the impact of deep sedation within 48 hours of initiation of mechanical ventilation, as described in the world’s literature. The primary outcome was mortality. Secondary outcomes included hospital and ICU lengths of stay, mechanical ventilation duration, and delirium and tracheostomy frequency. Data Sources: The following data sources were searched: MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstract: s of Reviews and Effects, Cochrane Database of Systematic Reviews databases, Clinical-Trials.gov, conference proceedings, and reference lists. Study Selection: Randomized controlled trials and nonrandomized studies were included. Data Extraction: Two reviewers independently screened abstracts of identified studies for eligibility. Data Synthesis: Nine studies (n = 4,521 patients) published between 2012 and 2017 were included. A random effects metaanalytic model revealed that early light sedation was associated with lower mortality (9.2%) versus deep sedation (27.6%) (odds ratio, 0.34 [0.21-0.54]). Light sedation was associated with fewer mechanical ventilation (mean difference,-2.1; 95% CI,-3.6 to-0.5) and ICU days (mean difference,-3.0 (95% CI,-5.4 to-0.6). Delirium frequency was 28.7% in the light sedation group and 48.5% in the deep sedation group, odds ratio, 0.50 (0.22-1.16). Conclusions: Deep sedation in mechanically ventilated patients, as evaluated in a small number of qualifying heterogeneous randomized controlled trials and observational studies, was associated with increased mortality and lengths of stay. Interventions targeting early sedation depth assessment, starting in the emergency department and subsequent ICU admission, deserve further investigation and could improve outcome. (Crit Care Med 2018; 46:471-479) Copyright © 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Author Keywords
Analgesia;  Mechanical ventilation;  Meta-analysis;  Sedation

Document Type: Article
Source: Scopus

“Sexuality and Intimacy Following Stroke: Perspectives of Partners” (2018) Sexuality and Disability

Sexuality and Intimacy Following Stroke: Perspectives of Partners
(2018) Sexuality and Disability, . Article in Press. 

Kniepmann, K., Kerr, S.

School of Medicine, Program in Occupational Therapy, Washington University in St. Louis, 4444 Forest Park Avenue, Campus Box 8505, St. Louis, MO 63108, United States

Abstract
Intimacy and sexuality can make vital contributions to quality of life but may become complicated or problematic for stroke survivors and their partners/spouses. Several studies have focused on survivor feelings and perceptions of post-stroke sexuality, but partners are generally neglected. The purpose of this project is to identify partner perspectives and experiences related to intimacy and sexuality following a stroke. Nine participants were interviewed in person or by phone about relationship changes and their information, supports or resources regarding intimacy and sexuality. Transcripts were analyzed using techniques of thematic analysis. Four themes were identified: (1) maintaining closeness and togetherness, (2) redefining sexuality and intimacy after stroke, (3) coping with lack of resources, and (4) wishing health professionals would discuss these topics. Results of this study indicated that partners are very concerned about intimacy and sexuality but feel unprepared to address these personal concerns post-stroke. Clinicians can open the lines of communication about sexuality and intimacy to support couples’ quality of life. Further resources and training as well as policies need to be developed to address sexuality and intimacy effectively with stroke survivors and their partners. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Author Keywords
Family caregiver;  Intimacy;  Quality of life;  Sexuality;  Stroke;  United States

Document Type: Article in Press
Source: Scopus

“Principles of cross-network communication in human resting state fMRI” (2018) Scandinavian Journal of Psychology

Principles of cross-network communication in human resting state fMRI
(2018) Scandinavian Journal of Psychology, 59 (1), pp. 83-90. 

Mitra, A.a , Raichle, M.E.a b

a Department of Radiology, Washington University, St Louis, MO, United States
b Department of Neurology, Washington University, St Louis, MO, United States

Abstract
Directed signaling among and within the large-scale networks of the human brain is functionally critical. Recent advances in our understanding of spontaneous fluctuations of the fMRI BOLD signal have provided strategies to study the spatial-temporal properties of directed signaling at infra-slow frequencies. Herein we explore the relationship between two canonical systems of the human brain, the default mode network (DMN) and the dorsal attention network (DAN) whose anti-correlated relationship is well known but poorly understood. We find that within the DMN, activity moves from retrosplenial to prefrontal cortex whereas in the DAN activity moves from the frontal eye fields to the parietal cortex. Bi-directional communication between the two networks occurs via their earliest elements (i.e., from the retrosplenial cortex of the DMN to the frontal eye fields of the DAN). This framework for network communication appears to generalize across all networks providing an expanded basis for understanding human brain function. © 2018 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Author Keywords
Communication;  Networks;  Propagation;  Spontaneous activity;  Systems;  Wave

Document Type: Article
Source: Scopus

“Functional Outcomes of an Interdisciplinary Outpatient Rehabilitation Program for Patients with Malignant Brain Tumors” (2018) PM and R

Functional Outcomes of an Interdisciplinary Outpatient Rehabilitation Program for Patients with Malignant Brain Tumors
(2018) PM and R, . Article in Press. 

Shahpar, S.a , Wong, A.W.K.b , Keeshin, S.c , Eickmeyer, S.M.d , Semik, P.e , Kocherginsky, M.f , McCarty, S.c

a Northwestern University Feinberg School of Medicine, Chicago, IL; and Shirley Ryan AbilityLab, 355 E. Erie Street, Chicago, IL 60611, United States
b Washington University School of Medicine, St Louis, MO, United States
c Northwestern University Feinberg School of Medicine, Chicago, IL; and Shirley Ryan AbilityLab, Chicago, IL, United States
d Department of Physical Medicine and Rehabilitation, University of Kansas School of Medicine, Kansas City, KS, United States
e Center of Rehabilitation Outcomes Research, Shirley Ryan AbilityLab, Chicago, IL, United States
f Department of Preventive Medicine, Division of Biostatistics, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Abstract
Background: Malignant brain tumors cause significant impairments in function because of the nature of the disease. Nevertheless, patients with malignant brain tumors can make functional gains equivalent to those with stroke and traumatic brain injury in the inpatient rehabilitation setting. However, the efficacy of outpatient rehabilitation in this population has received little study. Objective: To determine if an interdisciplinary outpatient rehabilitation program will improve functional outcomes in patients with malignant brain tumors. Design: Nonrandomized prospective longitudinal study. Setting: Six affiliated outpatient sites of one institution. Patients: Forty-nine adults with malignant brain tumors were enrolled. Methods: Patients received interdisciplinary therapy services, with duration determined by the therapist evaluations. The therapists scored the Day Rehabilitation Outcome Scale (DayROS) and Disability Rating Scale (DRS) on admission and discharge. The caregivers filled out the DRS at discharge, 1 month, and 3 months after discharge. Main Outcome Measurements: The primary study outcome measure was the DayROS, which is a functional measure similar to the Functional Independence Measure. DRS was another functional outcome measure assessing basic self-care, dependence on others, and psychosocial adaptability. Results: Forty-six of 49 enrolled patients (94%) completed the day rehabilitation program. The average length of stay was 76.9 days. There was a significant improvement in total DayROS (P < .001), mobility (P < .001), Activities of Daily Living ( P < .001), and communication (P < .001) DayROS subscores from admission to discharge. There were no significant changes over time in the DRS scores. Women had higher DayROS gains (P = .003) and better therapist DRS scores from admission to discharge than men (P = .010). Conclusions: Patients with malignant brain tumors can make functional gains in an interdisciplinary outpatient rehabilitation program. This level of care should be considered in this patient population. Level of Evidence: II © 2018

Author Keywords
brain tumor;  cancer rehabilitation;  Function;  rehabilitation

Document Type: Article in Press
Source: Scopus