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WUSTL Neuroscience Publications Archive - February 2016

February 2016

February 25, 2016
 
Waddell, K.J.a , Birkenmeier, R.L.a b c , Bland, M.D.a b c , Lang, C.E.a b c 
An exploratory analysis of the self-reported goals of individuals with chronic upper-extremity paresis following stroke
(2016) Disability and Rehabilitation, 38 (9), pp. 853-857. 

DOI: 10.3109/09638288.2015.1062926

a Program in Physical Therapy, Washington University, School of Medicine, Campus Box 8502, 4444 Forest Park Ave, St. Louis, MO, United States
b Program in Occupational Therapy, Washington University, St. Louis, MO, United States
c Department of Neurology, Washington University, St. Louis, MO, United States

Abstract
Purpose: To classify the self-identified goals of individuals post-stroke with chronic upper extremity (UE) paresis, and determine if age, UE functional capacity and pre-stroke hand dominance influence overall goal selection. Method: Sixty-five subjects participated. Using the Canadian Occupational Performance Measure (COPM) to establish treatment goals, the top five goals were categorized using the Occupational Therapy Practice Framework into five categories: activities of daily living (ADLs), instrumental activities of daily living (IADLs), leisure, work and general UE movement. A Chi-square analysis determined if age, UE functional capacity (measured by the Action Research Arm Test) and UE hand dominance influenced individual goal selection. Results: The majority of goals were in the ADL (37%) and IADL (40%) categories. A small percentage (12%) was related to general UE movement. Individuals with moderate UE functional capacity identified more ADL goals than those with higher UE functional capacity. There was not a difference between age and UE dominance across all five goal areas. Conclusions: Individuals with chronic UE paresis had specific goals that were not influenced by age or hand dominance, but partially influenced by severity. General UE movement goals were identified less than goals related to specific activities. ? Implications for Rehabilitation • Considering the specificity of individual goals following stroke, it is recommended that clinicians regularly utilize a goal setting tool to help establish client goals. • It is recommended that clinicians further inquire about general goals in order to link upper extremity deficits to functional activity limitations. • Age, upper extremity functional capacity and hand dominance have little influence on the rehabilitation goals for individuals with chronic paresis after stroke. © 2015 Informa UK Ltd.

Author Keywords
Function;  goal setting;  movement;  stroke;  upper extremity

Document Type: Article
Source: Scopus
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Schwantes-An, T.-H.a b , Zhang, J.a bq , Chen, L.-S.c , Hartz, S.M.c , Culverhouse, R.C.d , Chen, X.e , Coon, H.f , Frank, J.g , Kamens, H.M.h i j , Konte, B.k , Kovanen, L.l , Latvala, A.m , Legrand, L.N.n , Maher, B.S.o , Melroy, W.E.h i , Nelson, E.C.c , Reid, M.W.p , Robinson, J.D.q , Shen, P.-H.r , Yang, B.-Z.s , Andrews, J.A.p , Aveyard, P.t , Beltcheva, O.u , Brown, S.A.v , Cannon, D.S.f , Cichon, S.w x , Corley, R.P.h , Dahmen, N.y , Degenhardt, L.z aa , Foroud, T.ab , Gaebel, W.ac , Giegling, I.k , Glatt, S.J.ad , Grucza, R.A.c , Hardin, J.ae , Hartmann, A.M.k , Heath, A.C.c , Herms, S.w x , Hodgkinson, C.A.r , Hoffmann, P.w x , Hops, H.p , Huizinga, D.ag , Ising, M.ah , Johnson, E.O.ai , Johnstone, E.aj , Kaneva, R.P.u , Kendler, K.S.e , Kiefer, F.ak, Kranzler, H.R.al , Krauter, K.S.h am , Levran, O.an , Lucae, S.ah , Lynskey, M.T.ao , Maier, W.af , Mann, K.ap , Martin, N.G.aq , Mattheisen, M.w ar as , Montgomery, G.W.aq , Müller-Myhsok, B.ah , Murphy, M.F.at , Neale, M.C.e , Nikolov, M.A.c u , Nishita, D.ae , Nöthen, M.M.w , Nurnberger, J.au , Partonen, T.l , Pergadia, M.L.c , Reynolds, M.av , Ridinger, M.aw bo , Rose, R.J.ax , Rouvinen-Lagerström, N.l , Scherbaum, N.ay , Schmäl, C.ap , Soyka, M.az ba , Stallings, M.C.h bb , Steffens, M.bc , Treutlein, J.g , Tsuang, M.v , Wall, T.L.v , Wodarz, N.aw , Yuferov, V.an , Zill, P.bd , Bergen, A.W.ae , Chen, J.e , Cinciripini, P.M.q , Edenberg, H.J.be , Ehringer, M.A.h i , Ferrell, R.E.bf , Gelernter, J.s bg bh , Goldman, D.r , Hewitt, J.K.h bb , Hopfer, C.J.bi , Iacono, W.G.n , Kaprio, J.l m bj , Kreek, M.J.an , Kremensky, I.M.u , Madden, P.A.F.c , McGue, M.n , Munafò, M.R.bk , Philibert, R.A.bl , Rietschel, M.g , Roy, A.bm , Rujescu, D.k , Saarikoski, S.T.l , Swan, G.E.bp , Todorov, A.A.c , Vanyukov, M.M.av , Weiss, R.B.bn , Bierut, L.J.c , Saccone, N.L.a 
Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts
(2016) Behavior Genetics, 46 (2), pp. 151-169. 

DOI: 10.1007/s10519-015-9737-3

a Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, United States
b Genometrics Section, Computational and Statistical Genomics Branch, Division of Intramural Research, National Human Genome Research Institute, US National Institutes of Health (NIH), Baltimore, MD, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States
f Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, United States
g Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany
h Institute for Behavioral Genetics, University of Colorado, Boulder, CO, United States
i Department of Integrative Physiology, University of Colorado, Boulder, CO, United States
j Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, United States
k Department of Psychiatry, Universitätsklinikum Halle (Saale), Halle (Saale), Germany
l Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
m Department of Public Health, University of Helsinki, Helsinki, Finland
n Department of Psychology, University of Minnesota, Minneapolis, MN, United States
o Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States
p Oregon Research Institute, Eugene, OR, United States
q Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
r Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United States
s Department of Psychiatry, Yale University, New Haven, CT, United States
t Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom
u Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria
v Department of Psychiatry, University of California San Diego, La Jolla, CA, United States
w Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany
x Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
y Ökumenisches Hainich-Klinikum, Mühlhausen/Thüringen, Germany
z National Drug and Alcohol Research Centre, University of New South Wales, Randwick, NSW, Australia
aa School of Population and Global Health, University of Melbourne, Melbourne, Australia
ab Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
ac University of Düsseldorf, Düsseldorf, Germany
ad Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, United States
ae Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, United States
af University of Bonn, Bonn, Germany
ag Institute of Behavioral Science, University of Colorado, 80309, Boulder, CO, United States
ah Max-Planck-Institute of Psychiatry, Munich, Germany
ai Behavioral Health Research Division, Research Triangle Institute International, Durham, NC, United States
aj Department of Oncology, University of Oxford, Oxford, United Kingdom
ak Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany
al Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
am Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, United States
an Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, United States
ao Addictions Department, Institute of Psychiatry, King’s College London, London, United Kingdom
ap Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany
aq Department of Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, Australia
ar Harvard School of Public Health, Boston, MA, United States
as Aarhus University, Aarhus, Denmark
at Childhood Cancer Research Group, University of Oxford, Oxford, United Kingdom
au Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States
av Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, United States
aw Department of Psychiatry, University Medical Center Regensburg, University of Regensburg, Regensburg, Germany
ax Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States
ay Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR Hospital Essen, University of Duisburg-Essen, Essen, Germany
az Department of Psychiatry, University of Munich, Munich, Germany
ba Private Hospital Meiringen, Meiringen, Switzerland
bb Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, United States
bc Research Department, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, Bonn, Germany
bd University of Munich, Munich, Germany
be Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
bf Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, United States
bg Department of Genetics, Yale University, New Haven, CT, United States
bh Department of Neurobiology, Yale University, New Haven, CT, United States
bi Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
bj Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland
bk MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies, and School of Experimental Psychology, University of Bristol, Bristol, United Kingdom
bl Department of Psychiatry, University of Iowa, Iowa City, IA, United States
bm Psychiatry Service, Department of Veteran Affairs, New Jersey VA Health Care System, East Orange, NJ, United States
bn Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, United States
bo Psychiatric Hospital, Konigsfelden, Windisch, Switzerland
bp Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, United States
bq Key Laboratory of Brain Function and Disease, School of Life Sciences, Chinese Academy of Sciences, University of Science and Technology of China, Hefei, Anhui, China

Abstract
The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for “general” substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95 % C.I. [0.83–0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses. © 2015, Springer Science+Business Media New York.

Author Keywords
Addiction;  Genetic association;  Opioid receptor;  OPRM1;  Single nucleotide polymorphism (SNP);  Substance dependence

Document Type: Article
Source: Scopus
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van den Berg, S.M.a , de Moor, M.H.M.b c d , Verweij, K.J.H.e f , Krueger, R.F.g , Luciano, M.h i , Arias Vasquez, A.j k l m , Matteson, L.K.g , Derringer, J.n , Esko, T.o , Amin, N.p , Gordon, S.D.e , Hansell, N.K.e , Hart, A.B.q , Seppälä, I.r , Huffman, J.E.s , Konte, B.t , Lahti, J.u v , Lee, M.w , Miller, M.g , Nutile, T.x , Tanaka, T.y , Teumer, A.z , Viktorin, A.aa , Wedenoja, J.ab , Abdellaoui, A.b , Abecasis, G.R.ac , Adkins, D.E.ad , Agrawal, A.ae , Allik, J.af ag , Appel, K.ah , Bigdeli, T.B.w , Busonero, F.ai , Campbell, H.aj , Costa, P.T.ak , Smith, G.D.al , Davies, G.h i , de Wit, H.am , Ding, J.bo , Engelhardt, B.E.an , Eriksson, J.G.v ao ap aq ar , Fedko, I.O.b , Ferrucci, L.y , Franke, B.j k l , Giegling, I.t , Grucza, R.ae , Hartmann, A.M.t , Heath, A.C.ae , Heinonen, K.u , Henders, A.K.e , Homuth, G.as , Hottenga, J.-J.b , Iacono, W.G.g , Janzing, J.k , Jokela, M.u , Karlsson, R.aa , Kemp, J.P.al at , Kirkpatrick, M.G.am , Latvala, A.ab ao , Lehtimäki, T.r , Liewald, D.C.h i , Madden, P.A.F.ae , Magri, C.au , Magnusson, P.K.E.aa , Marten, J.s , Maschio, A.ai , Mbarek, H.b , Medland, S.E.e , Mihailov, E.o av , Milaneschi, Y.aw , Montgomery, G.W.e , Nauck, M.ax , Nivard, M.G.b , Ouwens, K.G.b , Palotie, A.ay az , Pettersson, E.aa , Polasek, O.ba , Qian, Y.bo , Pulkki-Råback, L.u , Raitakari, O.T.bb bc , Realo, A.af , Rose, R.J.bd , Ruggiero, D.x , Schmidt, C.O.z , Slutske, W.S.be , Sorice, R.x , Starr, J.M.i bf , St Pourcain, B.al bg bh , Sutin, A.R.y bi , Timpson, N.J.al , Trochet, H.s , Vermeulen, S.l bj , Vuoksimaa, E.ab , Widen, E.az , Wouda, J.a b , Wright, M.J.e , Zgaga, L.aj bk , Generation Scotlandbl , Porteous, D.bm , Minelli, A.au , Palmer, A.A.q am , Rujescu, D.t , Ciullo, M.x , Hayward, C.s , Rudan, I.aj , Metspalu, A.o ag , Kaprio, J.ab ao az , Deary, I.J.h i , Räikkönen, K.u , Wilson, J.F.s aj , Keltikangas-Järvinen, L.u , Bierut, L.J.ae , Hettema, J.M.w , Grabe, H.J.ah bn , Penninx, B.W.J.H.aw , van Duijn, C.M.p , Evans, D.M.al , Schlessinger, D.bo , Pedersen, N.L.aa , Terracciano, A.v y , McGue, M.g bp , Martin, N.G.e , Boomsma, D.I.b 
Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium
(2016) Behavior Genetics, 46 (2), pp. 170-182. 

DOI: 10.1007/s10519-015-9735-5

a Department of Research Methodology, Measurement and Data-Analysis (OMD), Faculty of Behavioural, Management, and Social Sciences, University of Twente, PO Box 217, Enschede, Netherlands
b Department of Biological Psychology, VU University Amsterdam, Amsterdam, Netherlands
c Department of Clinical Child and Family Studies, VU University Amsterdam, Amsterdam, Netherlands
d Department of Methods, VU University Amsterdam, Amsterdam, Netherlands
e QIMR Berghofer Medical Research Institute, Brisbane, Australia
f Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, Netherlands
g Department of Psychology, University of Minnesota, Minneapolis, United States
h Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom
i Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom
j Donders Institute for Cognitive Neuroscience, Radboud University Nijmegen, Nijmegen, Netherlands
k Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
l Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
m Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
n Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
o Estonian Genome Center, University of Tartu, Tartu, Estonia
p Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands
q Department of Human Genetics, University of Chicago, Chicago, IL, United States
r Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland
s MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom
t Department of Psychiatry, University of Halle, Halle, Germany
u Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland
v Folkhälsan Research Center, Helsinki, Finland
w Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States
x Institute of Genetics and Biophysics “A. Buzzati-Traverso” – CNR, Naples, Italy
y National Institute on Aging, NIH, Baltimore, MD, United States
z Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
aa Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
ab Department of Public Health, University of Helsinki, Helsinki, Finland
ac Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, United States
ad Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, VA, United States
ae Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
af Department of Psychology, University of Tartu, Tartu, Estonia
ag Estonian Academy of Sciences, Tallinn, Estonia
ah Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
ai Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy
aj Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
ak Behavioral Medicine Research Center, Duke University School of Medicine, Durham, NC, United States
al Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
am Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, United States
an Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, United States
ao National Institute for Health and Welfare (THL), Helsinki, Finland
ap Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
aq Unit of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
ar Vasa Central Hospital, Vaasa, Finland
as Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany
at Translational Research Institute, University of Queensland Diamantina Institute, Brisbane, Australia
au Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
av Department of Biotechnology, University of Tartu, Tartu, Estonia
aw Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands
ax Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
ay Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
az Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
ba Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia
bb Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
bc Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
bd Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN, United States
be Department of Psychological Sciences and Missouri Alcoholism Research Center, University of Missouri, Columbia, MO, United States
bf Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, United Kingdom
bg School of Oral and Dental Sciences, University of Bristol, Bristol, United Kingdom
bh School of Experimental Psychology, University of Bristol, Bristol, United Kingdom
bi College of Medicine, Florida State University, Tallahassee, FL, United States
bj Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands
bk Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland
bl Scottish Family Health Study, A Collaboration Between the University Medical Schools and NHS, Aberdeen, Dundee, Edinburgh and Glasgow, United Kingdom
bm Medical Genetics Section, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh, United Kingdom
bn Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany
bo Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States
bp Institute of Public Health, University of Southern Denmark, Odense, Denmark

Abstract
Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion. © 2015, The Author(s).

Author Keywords
Common genetic variants;  Imputation;  Personality;  Phenotype harmonization;  Polygenic risk

Document Type: Article
Source: Scopus
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McCollum, M.a b , LaVesser, P.a c , Berg, C.a 
Participation in Daily Activities of Young Adults with High Functioning Autism Spectrum Disorder
(2016) Journal of Autism and Developmental Disorders, 46 (3), pp. 987-997. 

DOI: 10.1007/s10803-015-2642-z

a Washington University School of Medicine, St. Louis, MO, United States
b St. John’s Children’s Hospital, 800 E Carpenter St, Springfield, IL, United States
c University of Colorado Denver, Denver, CO, United States

Abstract
Young adults with an autism spectrum disorder (ASD) struggle to assume adult roles. This research assessed the feasibility of using the Adolescent and Young Adult Activity Card Sort (AYA-ACS) with emerging adults with high functioning ASD. Two phases were utilized during this research: (1) comparing the activity participation reported by emerging adults with an ASD and that reported by their caring adult; (2) examining the barriers to participation reported. Preliminary results demonstrate that the AYA-ACS appears to be a reliable and valid method of identifying emerging adults’ participation strengths as well as personal and environmental challenges in a variety of age-appropriate activities. The AYA-ACS could assist service providers by providing an understanding of the challenges to participation faced by this population and aid in developing client centered interventions. © 2015, Springer Science+Business Media New York.

Author Keywords
Activity card sort;  Activity involvement;  Autism spectrum disorder;  Emerging adults;  Engagement;  Participation;  Transition age;  Young adults

Document Type: Article
Source: Scopus
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Hong, B.A.a , Robiner, W.N.b 
Psychologists in Academic Health Centers and Medical Centers: Being Visible, Relevant and Integral
(2016) Journal of Clinical Psychology in Medical Settings, pp. 1-10. Article in Press. 

DOI: 10.1007/s10880-016-9450-2

a Washington University School of Medicine, St. Louis, United States
b University of Minnesota Medical School, Minneapolis, United States

Abstract
Psychologists play key roles in academic health centers. This article is an outgrowth of a presentation at the 2015 Conference of the Association of Psychologists in Academic Health Centers addressing various strategies by which psychologists can effectively adapt to and develop successful careers in medical schools, academic health centers, and teaching hospitals. The authors encourage early career and mid-career psychologists in academic health centers to be active, engaged members of their institutions and to participate in multiple aspects of the research, educational, and clinical missions. © 2016 Springer Science+Business Media New York

Author Keywords
Academic Health Centers;  Career;  Health Psychology;  Medical Schools

Document Type: Article in Press
Source: Scopus
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Hutchison, K.A.a , Bugg, J.M.b , Lim, Y.B.b , Olsen, M.R.a 
Congruency precues moderate item-specific proportion congruency effects
(2016) Attention, Perception, and Psychophysics, pp. 1-17. Article in Press. 

DOI: 10.3758/s13414-016-1066-y

a Department of Psychology, Montana State University, Bozeman, MT, United States
b Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States

Abstract
The item-specific proportion congruency (ISPC) effect refers to the reduction in the Stroop effect for items (e.g., words) that mostly appear in an incongruent format, as compared to items that mostly appear in a congruent format. It is thought to demonstrate reactive control of word-reading processes. In the present study, we tested the hypothesis that using explicit, trial-by-trial congruency precues to proactively guide attention during a color-word Stroop task could reduce the otherwise robust ISPC effect. In Experiment 1, the precueing manipulation was employed alongside a manipulation traditionally thought to influence proactive control of word-reading processes (i.e., list proportion congruence [list PC]). Precueing participants with 100 %-valid precues eliminated both the ISPC effect and the list PC effect. In Experiment 2, we used 70 %-valid congruency precues to direct participants to generally expect conflict or congruence on a given trial. ISPC effects were selectively reduced when the participants expected conflict. These results suggest that precueing influences engagement in proactive control and, as a result, reduces the impact of item-specific and list-based tendencies to direct attention toward or away from word reading. © 2016 The Psychonomic Society, Inc.

Author Keywords
Item-specific proportion congruency;  Preparatory cues;  Stroop

Document Type: Article in Press
Source: Scopus
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Gonthier, C.a , Braver, T.S.b , Bugg, J.M.b 
Dissociating proactive and reactive control in the Stroop task
(2016) Memory and Cognition, pp. 1-11. Article in Press. 

DOI: 10.3758/s13421-016-0591-1

a Université Savoie Mont Blanc, LPNC UMR CNRS 5105, Chambéry, France
b Department of Psychological and Brain Sciences, Washington University in Saint Louis, Campus Box 1125, One Brookings Dr., St. Louis, MO, United States

Abstract
The Dual Mechanisms of Control framework posits the existence of two distinct control mechanisms, proactive and reactive, which may operate independently. However, this independence has been difficult to study with most experimental paradigms. The Stroop task may provide a useful way of assessing the independence of control mechanisms because the task elicits two types of proportion congruency effects, list-wide and item-specific, thought to reflect proactive and reactive control respectively. The present research tested whether these two proportion congruency effects can be used to dissociate proactive and reactive control. In 2 separate participant samples, we demonstrate that list-wide and item-specific proportion congruency effects are stable, exist in the same participants, and appear in different task conditions. Moreover, we identify two distinct behavioral signatures, the congruency cost and the transfer cost, which doubly dissociate the two effects. Together, the results are consistent with the view that proactive and reactive control reflect independent mechanisms. © 2016 Psychonomic Society, Inc.

Author Keywords
Cognitive control;  Dual Mechanisms of Control (DMC);  Item-specific proportion congruency;  List-wide proportion congruency;  Stroop interference

Document Type: Article in Press
Source: Scopus
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Chen, Y., Cai, A., Fritz, B.A., Dexter, F., Pryor, K.O., Jacobsohn, E., Glick, D.B., Willingham, M.D., Escallier, K.E., Winter, A.C., Avidan, M.S.
Amnesia of the Operating Room in the B-Unaware and BAG-RECALL Clinical Trials
(2016) Anesthesia and Analgesia, . Article in Press. 

DOI: 10.1213/ANE.0000000000001175

From the *Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri; †Division of Management Consulting, Department of Anesthesia, University of Iowa, Iowa City, Iowa; ‡Department of Anesthesiology, Weill Cornell Medical College, New York, New York; §Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; ?Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois; and ¶Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Abstract
BACKGROUND:: Patient memories of the operating room (OR) may serve as the informational basis for assessing satisfaction with individual anesthesiologists. Furthermore, the provision of clinically important information may assume that perioperative memories are retained. Studies assessing the extent of perioperative amnesia and factors associated with perioperative amnesia are sparse. Therefore, we assessed patient amnesia of the OR and of the preoperative holding area in hospitals where midazolam is typically administered in the preoperative holding area and evaluated whether midazolam dose administered in the preoperative holding area and patient age were associated with amnesia of the OR before induction of anesthesia. METHODS:: This was a retrospective study among 7750 adult patients who had general anesthesia and participated in the B-Unaware and Bispectral Index or Anesthetic Gas to Reduce Explicit Recall (BAG-RECALL) clinical trials. The last location the patient remembered before induction of anesthesia and the first location they remembered after induction of anesthesia were determined through a modified Brice questionnaire administered over the phone 30 days postoperatively. Regarding the preoperative period, patients were excluded if their last memory was unclear with respect to location before induction of anesthesia or if they were recruited at Winnipeg, where midazolam was typically first administered in the OR. Midazolam dose (mg/kg) administered in the preoperative holding area was divided into quartiles. Poisson regression models were used to calculate age- and multivariable-adjusted odds ratios (95% confidence intervals [CIs]) for the association between midazolam dose and amnesia of the OR before induction of anesthesia. RESULTS:: Of the 5339 patients included, 59.5% (95% CI, 58.2–60.9) of patients had amnesia of the OR before induction of anesthesia. In addition, 44.1% (95% CI, 42.8–45.7) last remembered the preoperative holding area, and 15.4% (95% CI, 14.4–16.4) only had preoperative memories before the holding area. The percentages of patients with amnesia of the OR before induction of anesthesia differed according to age groups: 50.7% (95% CI, 47.7%–53.7%) in patients aged 18 to 47 years versus 70.0% (95% CI, 67.0%–72.9%) in patients aged 73 to 99 years. Patients in the highest midazolam quartile had an adjusted prevalence ratio of 1.31 (95% CI, 1.22–1.42) for amnesia of the OR compared with those who did not receive midazolam. CONCLUSIONS:: In hospitals where patients typically receive midazolam in the preoperative holding area, the majority of patients do not remember the OR, and a clinically relevant number of patients does not remember the preoperative holding area. If additional studies produce results indicating that a substantial proportion of patients has amnesia of the anesthesiologist, these findings would argue against the validity of assessing patient satisfaction with individual anesthesiologists providing exclusively OR care in such hospitals. Furthermore, if additional studies yield findings suggesting patient amnesia of the preoperative holding area, these results would suggest reconsideration of providing clinically important information only in the preoperative holding area. Older age and midazolam-induced anterograde amnesia are probably associated with impaired perioperative memories. © 2016 International Anesthesia Research Society

Document Type: Article in Press
Source: Scopus
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Kang, S.-K.a b , Murphy, R.K.J.c , Hwang, S.-W.d , Lee, S.M.a b , Harburg, D.V.a b , Krueger, N.A.a , Shin, J.b e , Gamble, P.c , Cheng, H.f , Yu, S.b e , Liu, Z.g , McCall, J.G.h , Stephen, M.c , Ying, H.a , Kim, J.a b , Park, G.i j , Webb, R.C.a b , Lee, C.H.k, Chung, S.a b , Wie, D.S.l , Gujar, A.D.c , Vemulapalli, B.c , Kim, A.H.c , Lee, K.-M.j , Cheng, J.a , Huang, Y.m , Lee, S.H.n , Braun, P.V.a b o , Ray, W.Z.c , Rogers, J.A.a b o 
Bioresorbable silicon electronic sensors for the brain
(2016) Nature, 530 (7588), pp. 71-76. 

DOI: 10.1038/nature16492

a Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States
b Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL, United States
c Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO, United States
d KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, South Korea
e Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States
f Department of Engineering Science and Mechanics, Materials Research Institute, Pennsylvania State University, University Park, PA, United States
g Institute of High Performance Computing, Singapore, Singapore
h Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, United States
i Department of Biomicrosystem Technology, Korea University, Seoul, South Korea
j Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea
k Weldon School of Biomedical Engineering, School of Mechanical Engineering, Center for Implantable Devices, Birck Nanotechnology Center, Purdue University, West Lafayette, IN, United States
l School of Mechanical Engineering, Purdue University, West Lafayette, IN, United States
m Department of Mechanical Engineering, Civil and Environmental Engineering, Materials Science and Engineering, Skin Disease Research Center, Northwestern University, Evanston, IL, United States
n Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, South Korea
o Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States

Abstract
Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine. © 2016 Macmillan Publishers Limited. All rights reserved.

Document Type: Article
Source: Scopus
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Wu, X.a , Fleming, A.a b , Ricketts, T.a , Pavel, M.a , Virgin, H.c , Menzies, F.M.a , Rubinsztein, D.C.a 
Autophagy regulates Notch degradation and modulates stem cell development and neurogenesis
(2016) Nature Communications, 7, art. no. 10533, . 

DOI: 10.1038/ncomms10533

a Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
b Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, United Kingdom
c Department of Pathology and Immunology, Washington University, School of Medicine, St Louis, MO, United States

Abstract
Autophagy is a conserved, intracellular, lysosomal degradation pathway. While mechanistic aspects of this pathway are increasingly well defined, it remains unclear how autophagy modulation impacts normal physiology. It is, however, becoming clear that autophagy may play a key role in regulating developmental pathways. Here we describe for the first time how autophagy impacts stem cell differentiation by degrading Notch1. We define a novel route whereby this plasma membrane-resident receptor is degraded by autophagy, via uptake into ATG16L1-positive autophagosome-precursor vesicles. We extend our findings using a physiologically relevant mouse model with a hypomorphic mutation in Atg16L1, a crucial autophagy gene, which shows developmental retention of early-stage cells in various tissues where the differentiation of stem cells is retarded and thus reveal how modest changes in autophagy can impact stem cell fate. This may have relevance for diverse disease conditions, like Alzheimer' s Disease or Crohn' s Disease, associated with altered autophagy.

Document Type: Article
Source: Scopus
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Vincent, K.a b , Cornea, V.M.a b , Jong, Y.-J.I.c , Laferriere, A.a b , Kumar, N.a b , Mickeviciute, A.a b , Fung, J.S.T.a b , Bandegi, P.a b , Ribeiro-Da-Silva, A.a d , O'Malley, K.L.c , Coderre, T.J.a b 
Intracellular mGluR5 plays a critical role in neuropathic pain
(2016) Nature Communications, 7, art. no. 10604, . 

DOI: 10.1038/ncomms10604

a Alan Edwards Centre for Research on Pain, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, Canada
b Department of Anesthesia, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, Canada
c Department of Anatomy and Neurobiology, Washington University, School of Medicine, 660 South Euclid Avenue, St Louis, MO, United States
d Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, Canada

Abstract
Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which 60% is located on nuclear membranes, where activation leads to sustained Ca2+ responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor-mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expression in vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain.

Document Type: Article
Source: Scopus
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Tong, B.a , Hornak, A.J.b , Maison, S.F.c , Ohlemiller, K.K.a , Liberman, M.C.c , Simmons, D.D.b 
Oncomodulin, an EF-hand Ca2 + buffer, is critical for maintaining cochlear function in mice
(2016) Journal of Neuroscience, 36 (5), pp. 1631-1635. 

DOI: 10.1523/JNEUROSCI.3311-15.2016

a Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, United States
c Eaton–Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Department of Otology and Laryngology, Harvard Medical School, Boston, MA, United States

Abstract
Oncomodulin (Ocm), a member of the parvalbumin family of calcium binding proteins, is expressed predominantly by cochlear outer hair cells in subcellular regions associated with either mechanoelectric transduction or electromotility. Targeted deletion of Ocm caused progressive cochlear dysfunction. Although sound-evoked responses are normal at 1 month, by 4 months, mutants show only minimal distortion product otoacoustic emissions and 70–80 dB threshold shifts in auditory brainstem responses. Thus, Ocm is not critical for cochlear development but does play an essential role for cochlear function in the adult mouse. © 2016 the authors.

Author Keywords
Calcium homeostasis;  Hearing loss;  Outer hair cell;  Parvalbumin

Document Type: Article
Source: Scopus
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Christensen, K.D.a , Roberts, J.S.b , Whitehouse, P.J.c , Royal, C.D.M.d , Obisesan, T.O.e , Cupples, L.A.f , Vernarelli, J.A.g , Bhatt, D.L.h , Linnenbringer, E.i , Butson, M.B.c , Fasaye, G.-A.j , Uhlmann, W.R.k , Hiraki, S.l , Wang, N.m , Cook-Deegan, R.n , Green, R.C.a 
Disclosing pleiotropic effects during genetic risk assessment for Alzheimer disease
(2016) Annals of Internal Medicine, 164 (3), pp. 155-163. Cited 1 time.

DOI: 10.7326/M15-0187

a Brigham and Women's Hospital and Harvard Medical School, Partners Personalized Medicine, EC Alumnae Building, 41 Avenue Louis Pasteur, Boston, MA, United States
b University of Michigan School of Public Health, 3854 SPH i, 1415 Washington Heights, Ann Arbor, MI, United States
c Case Western Reserve University, University Foley Elderhealth Center, 12200 Fairhill Road, Cleveland, OH, United States
d Duke University, Office of Undergraduate Scholars and Fellows, Smith Warehouse, 114 South Buchanan Street, Durham, NC, United States
e Howard University Hospital, Towers Building 5000, 2041 Georgia Avenue NW, Washington, DC, United States
f Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, United States
g Fairfield University, 1073 North Benson Road, Fairfield, CT, United States
h Brigham and Women's Hospital, 75 Francis Street, Boston, MA, United States
i Washington University School of Medicine, Division of Public Health Sciences, Department of Surgery, 660 South Euclid Avenue, St. Louis, MO, United States
j Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD, United States
k University of Michigan Medical School, Department of Human Genetics, 300 North Ingalls Building, NI3 A03, SPC 5419, Ann Arbor, MI, United States
l GeneDx, 207 Perry Parkway, Gaithersburg, MD, United States
m Boston University School of Public Health, CT340C, 801 Massachusetts Avenue, Boston, MA, United States
n Sanford School of Public Policy, Duke Box 90239, Durham, NC, United States

Abstract
Background: Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. Objective: To determine the safety and behavioral effect of disclosing modest associations between apolipoprotein E (APOE) genotype and coronary artery disease (CAD) risk during APOEbased genetic risk assessments for Alzheimer disease (AD). Design: Randomized, multicenter equivalence clinical trial. (ClinicalTrials.gov: NCT00462917) Setting: 4 teaching hospitals. Participants: 257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative. Intervention: Disclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only). Measurements: Primary outcomes were Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes were all measures at 6 weeks and 6 months and test-related distress and health behavior changes at 12 months. Results: At 12 months, mean BAI scores were 3.5 in both the AD-only and AD+CAD groups (difference, 0.0 [95% CI, -1.0 to 1.0]), and mean CES-D scores were 6.4 and 7.1 in the AD-only and AD+CAD groups, respectively (difference, 0.7 [CI, -1.0 to 2.4]). Both confidence bounds fell within the equivalence margin of ±5 points. Among carriers of the APOEε4 allele, distress was lower in the AD+CAD groups (difference, -4.8 [CI, -8.6 to -1.0]) (P = 0.031 for the interaction between group and APOE genotype). Participants in the AD+CAD groups also reported more health behavior changes, regardless of APOE genotype. Limitations: Outcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants. Conclusion: Disclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions. Providing risk modification information about CAD improved health behaviors. Findings highlight the potential benefits of disclosure of secondary genetic findings when options exist for decreasing risk. Primary Funding Source: National Human Genome Research Institute. © 2016 American College of Physicians.

Document Type: Article
Source: Scopus
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Chatterjee, P.a b c d , Lim, W.L.F.b c d , Shui, G.e , Gupta, V.B.b c d , James, I.f , Fagan, A.M.g h , Xiong, C.h i , Sohrabi, H.R.a b c d , Taddei, K.a b d , Brown, B.M.a b d , Benzinger, T.h j , Masters, C.k , Snowden, S.G.l , Wenk, M.R.m , Bateman, R.J.g h , Morris, J.C.g h , Martins, R.N.a b c d 
Plasma Phospholipid and Sphingolipid Alterations in Presenilin1 Mutation Carriers: A Pilot Study
(2016) Journal of Alzheimer's Disease, 50 (3), pp. 887-894. 

DOI: 10.3233/JAD-150948

a School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia
b McCusker Alzheimer's Research Foundation, Perth, WA, Australia
c The CRC for Mental Health, Australia
d School of Medical Science, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA, Australia
e State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
f Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia
g Department of Neurology, Washington University, St. Louis, MO, United States
h Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, United States
i Division of Biostatistics, Washington University, St. Louis, MO, United States
j Department of Radiology, Washington University, St. Louis, MO, United States
k Mental Health Research Institute, University of Melbourne, Melbourne, VA, Australia
l Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
m Department of Biochemistry and Department of Biological Sciences, National University of Singapore, Singapore

Abstract
Background and Objective: Aberrant lipid metabolism has been implicated in sporadic Alzheimer's disease (AD). The current study investigated plasma phospholipid and sphingolipid profiles in individuals carrying PSEN1 mutations responsible for autosomal dominant AD (ADAD). Methods: Study participants evaluated were from the Perth and Melbourne sites of the Dominantly Inherited Alzheimer Network (DIAN) study. Plasma phospholipid and sphingolipid profiles were measured using liquid chromatography coupled with mass spectrometry in 20 PSEN1 mutation carriers (MC; eight of whom were symptomatic and twelve asymptomatic, based on Clinical Dementia Rating scores) and compared with six non carriers (NC) using linear mixed models. Further, AD gold standard biomarker data obtained from the DIAN database were correlated with lipid species significantly altered between MC and NC, using Spearman's correlation coefficient. Results: One-hundred and thirty-nine plasma phospholipid and sphingolipid species were measured. Significantly altered species in MC compared to NC primarily belonged to choline and ethanolamine containing phospholipid classes and ceramides. Further phosphatidylcholine species (34:6, 36:5, 40:6) correlated with cerebrospinal fluid tau (p < 0.05), and plasmalogen ethanolamine species (34:2, 36:,4) correlated with both cerebrospinal fluid tau and brain amyloid load within the MC group (p < 0.05). Conclusion: These findings indicate altered phospholipid and sphingolipid metabolism in ADAD and provide insight into the pathomolecular changes occurring with ADAD pathogenesis. Further, findings reported in this study allow comparison of lipid alterations in ADAD with those reported previously in sporadic AD. The findings observed in the current pilot study warrant validation in the larger DIAN cohort. © 2016 - IOS Press and the authors. All rights reserved.

Author Keywords
Alzheimer's disease;  biomarkers;  familial Alzheimer's disease;  phospholipids;  sphingolipids

Document Type: Article
Source: Scopus
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Behrman-Lay, A.M.a , Paul, R.H.a b , Heaps-Woodruff, J.a b , Baker, L.M.a , Usher, C.a , Ances, B.M.c d e 
Human immunodeficiency virus has similar effects on brain volumetrics and cognition in males and females
(2016) Journal of NeuroVirology, 22 (1), pp. 93-103. 

DOI: 10.1007/s13365-015-0373-8

a Department of Psychology, University of Missouri- Saint Louis, St. Louis, MO, United States
b Missouri Institute of Mental Health, St. Louis, MO, United States
c Department of Neurology, Washington University in Saint Louis, 660 South Euclid Avenue, Campus Box 8111, St. Louis, MO, United States
d Department of Radiology, Washington University in Saint Louis, St. Louis, MO, United States
e Department of Biomedical Engineering, Washington University in Saint Louis, St. Louis, MO, United States

Abstract
Most studies that have examined neuropsychological impairments associated with human immunodeficiency virus (HIV) have focused on males, yet females represent one of the largest groups of newly infected patients. Further, few studies have examined neuropsychological performance and neuroimaging outcomes among females compared to males in the modern era of highly active anti-retroviral therapy (HAART). The present study investigated neuropsychological performance and brain volumetrics among HIV+ males (n = 93) and females (n = 44) on stable HAART compared to HIV seronegative (HIV−) males (n = 42) and females (n = 49). Results revealed a significant effect of HIV on neuropsychological performance and neuroimaging measures. An effect of gender, independent of HIV status, was also observed for neuroimaging measures but not neuropsychological performance. Additionally, no significant differences in neuropsychological performance or brain volumetrics were seen between HIV+ males and females. No significant interaction was observed between HIV and gender on either neuropsychological or neuroimaging indices. Our results suggest that both HIV+ males and females treated with HAART experience similar outcomes in terms of brain integrity. © 2015, Journal of NeuroVirology, Inc.

Author Keywords
Cognition;  Gender;  HIV;  Neuroimaging;  Neuropsychology;  Volumetrics

Document Type: Article
Source: Scopus
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Guha, A.a , Wang, L.a , Tanenbaum, A.a , Esmaeili-Firidouni, P.b , Wendelken, L.A.b , Busovaca, E.b , Clifford, K.b , Desai, A.b , Ances, B.M.a c d , Valcour, V.b 
Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60
(2016) Journal of NeuroVirology, 22 (1), pp. 80-87. 

DOI: 10.1007/s13365-015-0370-y

a Department of Neurology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
b Memory and Aging Center, Sandler Neurosciences Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, United States
c Department of Biomedical Engineering, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
d Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Individuals infected with HIV are living longer due to effective treatment with combination antiretroviral therapy (cART). Despite these advances, HIV-associated neurocognitive disorders (HAND) remain prevalent. In this study, we analyzed resting state functional connectivity (rs-fc) data from HIV-infected and matched HIV-uninfected adults aged 60 years and older to determine associations between HIV status, neuropsychological performance, and clinical variables. HIV-infected participants with detectable plasma HIV RNA exhibited decreased rs-fc within the salience (SAL) network compared to HIV-infected participants with suppressed plasma HIV RNA. We did not identify differences in rs-fc within HIV-infected individuals by HAND status. Our analysis identifies focal deficits in the SAL network that may be mitigated with suppression of plasma virus. However, these findings suggest that rs-fc may not be sensitive as a marker of HAND among individuals with suppressed plasma viral loads. © 2015, Journal of NeuroVirology, Inc.

Author Keywords
Cognition;  Functional MRI;  HIV;  Network connectivity

Document Type: Article
Source: Scopus
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Montine, T.J.a , Monsell, S.E.b , Beach, T.G.c , Bigio, E.H.d e , Bu, Y.b , Cairns, N.J.f , Frosch, M.g , Henriksen, J.a , Kofler, J.h , Kukull, W.A.b , Lee, E.B.i j k , Nelson, P.T.l m , Schantz, A.M.a , Schneider, J.A.n o p , Sonnen, J.A.a , Trojanowski, J.Q.i j k , Vinters, H.V.q r , Zhou, X.-H.b , Hyman, B.T.s t 
Multisite assessment of NIA-AA guidelines for the neuropathologic evaluation of Alzheimer's disease
(2016) Alzheimer's and Dementia, 12 (2), pp. 164-169. 

DOI: 10.1016/j.jalz.2015.07.492

a Department of Pathology, University of Washington, Seattle, WA, United States
b National Alzheimer Coordinating Center, University of Washington, Seattle, WA, United States
c Banner Sun Health Research Institute, Civin Laboratory for Neuropathology, Sun City, AZ, United States
d Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg, School of Medicine, Chicago, IL, United States
e Department of Pathology, Northwestern University Feinberg, School of Medicine, Chicago, IL, United States
f Department of Pathology and Immunology, Washington University, School of Medicine, St. Louis, MO, United States
g Department of Pathology, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charleston, MA, United States
h Department of Pathology, University of Pittsburgh, Pittsburgh, PA, United States
i Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA, United States
j Center for Neurodegenerative Disease Research, University of Pennsylvania, School of Medicine, Philadelphia, PA, United States
k Institute on Aging, University of Pennsylvania, School of Medicine, Philadelphia, PA, United States
l Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States
m Pathology Department, University of Kentucky, Lexington, KY, United States
n Department of Pathology, Rush University Medical Center, Chicago, IL, United States
o Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States
p Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States
q Department of Pathology, Laboratory Medicine (Neuropathology) David Geffen, School of Medicine, UCLA, Ronald Reagan UCLA Medical Center, Los Angeles, CA, United States
r Department of Neurology, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center, Los Angeles, CA, United States
s Department of Neurology, Massachusetts General Hospital, Charleston, MA, United States
t Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Charleston, MA, United States

Abstract
Introduction Neuropathologic assessment is the current "gold standard" for evaluating the Alzheimer's disease (AD), but there is no consensus on the methods used. Methods Fifteen unstained slides (8 brain regions) from each of the 14 cases were prepared and distributed to 10 different National Institute on Aging AD Centers for application of usual staining and evaluation following recently revised guidelines for AD neuropathologic change. Results Current practice used in the AD Centers Program achieved robustly excellent agreement for the severity score for AD neuropathologic change (average weighted κ =.88, 95% confidence interval: 0.77-0.95) and good-to-excellent agreement for the three supporting scores. Some improvement was observed with consensus evaluation but not with central staining of slides. Evaluation of glass slides and digitally prepared whole-slide images was comparable. Discussion AD neuropathologic evaluation as performed across AD Centers yields data that have high agreement with potential modifications for modest improvements. © 2016 The Alzheimer's Association.

Author Keywords
Alzheimer's disease;  Methods;  Multisite;  Neuropathology;  Whole-slide imaging

Document Type: Article
Source: Scopus
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Saito, A., Cavalli, V.
Signaling over distances
(2016) Molecular and Cellular Proteomics, 15 (2), pp. 382-393. Cited 2 times.

DOI: 10.1074/mcp.R115.052753

Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, United States

Abstract
Neurons are extremely polarized cells. Axon lengths often exceed the dimension of the neuronal cell body by several orders of magnitude. These extreme axonal lengths imply that neurons have mastered efficient mechanisms for long distance signaling between soma and synaptic terminal. These elaborate mechanisms are required for neuronal development and maintenance of the nervous system. Neurons can fine-Tune long distance signaling through calcium wave propagation and bidirectional transport of proteins, vesicles, and mRNAs along microtubules. The signal transmission over extreme lengths also ensures that information about axon injury is communicated to the soma and allows for repair mechanisms to be engaged. This review focuses on the different mechanisms employed by neurons to signal over long axonal distances and how signals are interpreted in the soma, with an emphasis on proteomic studies. We also discuss how proteomic approaches could help further deciphering the signaling mechanisms operating over long distance in axons. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Document Type: Article
Source: Scopus
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Jack, C.R., Jr.a , Knopman, D.S.b , Chételat, G.c , Dickson, D.d , Fagan, A.M.e , Frisoni, G.B.f , Jagust, W.g , Mormino, E.C.h , Petersen, R.C.b , Sperling, R.A.h , Van Der Flier, W.M.i , Villemagne, V.L.j , Visser, P.J.k , Vos, S.J.B.k 
Suspected non-Alzheimer disease pathophysiology-concept and controversy
(2016) Nature Reviews Neurology, 12 (2), pp. 117-124. 

DOI: 10.1038/nrneurol.2015.251

a Department of Radiology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN, United States
b Department of Neurology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN, United States
c INSERM, Université de Caen, EPHE, Caen, France
d Department of Pathology, Mayo Clinic and Foundation, 4500 San Pablo Road South, Jacksonville, FL, United States
e Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University, 4488 Forest Park Avenue, St Louis, MO, United States
f University Hospitals and University of Geneva, Rue Gabrielle-Perret-Gentil 4, Genève, Switzerland
g Helen Wills Neuroscience Institute, University of California Berkeley, 175 Li Ka Shing Center, Berkeley, CA, United States
h Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, United States
i Alzheimer Center, Department of Neurology, VU University Medical Center, PO Box 7057, Amsterdam, Netherlands
j Department of Molecular Imaging and Therapy, Centre for PET, Austin Health, 145 Studley Road, Melbourne, VIC, Australia
k Department of Psychiatry and Neuropsychology, Institute of Mental Health and Neuroscience, Maastricht University, PO Box 616 MD, Maastricht, Netherlands

Abstract
Suspected non-Alzheimer disease pathophysiology (SNAP) is a biomarker-based concept that applies to individuals with normal levels of amyloid-β biomarkers in the brain, but in whom biomarkers of neurodegeneration are abnormal. The term SNAP has been applied to clinically normal individuals (who do not meet criteria for either mild cognitive impairment or dementia) and to individuals with mild cognitive impairment, but is applicable to any amyloid-negative, neurodegeneration-positive individual regardless of clinical status, except when the pathology underlying neurodegeneration can be reliably inferred from the clinical presentation. SNAP is present in 23% of clinically normal individuals aged >65 years and in25% of mildly cognitively impaired individuals. APOEε 4 is underrepresented in individuals with SNAP compared with amyloid-positive individuals. Clinically normal and mildly impaired individuals with SNAP have worse clinical and/or cognitive outcomes than individuals with normal levels of neurodegeneration and amyloid-β biomarkers. In this Perspectives article, we describe the available data on SNAP and address topical controversies in the field. © 2016 Macmillan Publishers Limited.

Document Type: Review
Source: Scopus
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Kurth, C.
Anxiety, normative uncertainty, and social regulation
(2016) Biology and Philosophy, 31 (1), pp. 1-21. 

DOI: 10.1007/s10539-015-9508-9

Washington University in Saint Louis, St Louis, MO, United States

Abstract
Emotion plays an important role in securing social stability. But while emotions like fear, anger, and guilt have received much attention in this context, little work has been done to understand the role that anxiety plays. That’s unfortunate. I argue that a particular form of anxiety—what I call ‘practical anxiety’—plays an important, but as of yet unrecognized, role in norm-based social regulation. More specifically, it provides a valuable form of metacognition, one that contributes to social stability by helping individuals negotiate the challenges that come from having to act in the face of unclear norms. © 2015, Springer Science+Business Media Dordrecht.

Author Keywords
Anxiety;  Cooperation;  Emotion;  Fear;  Social regulation;  Uncertainty

Document Type: Article
Source: Scopus
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Jung, M.E.a , Wippold, F.J.b , Goebel, J.A.b 
Can high-resolution computed tomography detect a therapeutic response to medical treatment in a patient with otosclerosis?
(2016) Otology and Neurotology, 37 (2), pp. e7-e8. 

DOI: 10.1097/MAO.0000000000000863

a Department of Otolaryngology Head and Neck Surgery, Washington University School of Medicine, Box 8115, Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, Louis, MO, United States

Document Type: Short Survey
Source: Scopus
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Mattingly, G.a b , Anderson, R.b c 
Cariprazine for schizophrenia and bipolar I disorder
(2016) Current Psychiatry, 15 (1), pp. e1-e6. 

a Washington University in St. Louis, St. Louis, MO, United States
b Midwest Research Group, St. Charles, MO, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States

Document Type: Article
Source: Scopus
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Mattingly, G.a b , Anderson, R.b c 
Cariprazine for schizophrenia and bipolar I disorder
(2016) Current Psychiatry, 15 (2), pp. 34-39. 

a Washington University in St. Louis, St. Louis, MO, United States
b Midwest Research Group, St. Charles, MO, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States

Document Type: Article
Source: Scopus
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Sorkin, D.L.a , Buchman, C.A.b 
Cochlear implant access in six developed countries
(2016) Otology and Neurotology, 37 (2), pp. e161-e164. 

DOI: 10.1097/MAO.0000000000000946

a American Cochlear Implant Alliance, PO Box 103, McLean, VA, United States
b Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Background: Access to cochlear implantation varies greatly around the world. It is affected by factors that are specific to each country's health care system, by awareness, and by societal attitudes regarding deafness. Methods: Cochlear implant clinicians and researchers from six countries explored and discussed these variations and their likely causes: Robert Briggs from Australia; Wolfe-Dieter Baumgartner from Austria; Thomas Lenarz from Germany; Eva Koltharp from Sweden; Christopher Raine from the United Kingdom, and Craig Buchman, Donna Sorkin, and Christine Yoshinago from the United States. Results: Utilization rates are quite different for the pediatric and adult demographics in all six countries. Pediatric utilization ranges in the six countries (all in the developed world) ranged from a low of 50% in the United States to a high of 97% in Australia. Adult utilization is less than 10% everywhere in the world. Conclusions: Pediatric access to care was excellent for children with the exception of Germany and the United States where there is an inadequate referral system. Adult utilization was low everywhere because of the lack of screening for adults and the fact that primary care physicians and even audiologists are unfamiliar with CI candidacy criteria and outcomes, and hence typically do not make patient referrals. © 2015, Otology & Neurotology, Inc.

Author Keywords
Access to care;  Awareness;  Cochlear implants;  Utilization

Document Type: Conference Paper
Source: Scopus
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Johnson, K.J.a , Scheurer, M.E.b , Woehrer, A.c , Wiemels, J.d 
Evolving evidence on tumor and germline genetic classification of gliomas: Implications for etiology and survival studies
(2016) Clinical Neuropathology, 35 (1), pp. 31-38. 

DOI: 10.5414/NP300917

a Brown School Master of Public Health Program, Washington University, St. Louis, MO, United States
b Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, United States
c Institute of Neurology, Medical University of Vienna, Vienna, Austria
d Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, United States

Abstract
The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium that has the mission of fostering the development of multi-center and inter-disciplinary collaborations aiming to improve understanding of the etiology, outcomes, and prevention of brain tumors. Mayo Clinic faculty, Robert Jenkins, MD, PhD and Brian Patrick O'Neill, MD, hosted the 16th annual BTEC meeting on June 2*4, 2015, in Rochester, MN, USA. The meeting included presentations that emphasized the impact of new tumor classifications, methodological practices of population studies, as well as intra- and inter-tumoral molecular complexities on patient outcomes. The 2016 meeting will be held in Barcelona, Spain in June. © 2016 Dustri-Verlag Dr. K. Feistle.

Author Keywords
Brain tumor epidemiology consortium;  Brain tumors;  Genetic susceptibility;  Gliomas;  Meningiomas

Document Type: Article
Source: Scopus
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Pineda, R.G.a , Reynolds, L.C.a , Seefeldt, K.b , Hilton, C.L.c , Rogers, C.E.a , Inder, T.E.d 
Head lag in infancy: What is it telling us?
(2016) American Journal of Occupational Therapy, 70 (1), . 

DOI: 10.5014/ajot.2016.017558

a Program in Occupational Therapy, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
b Lighthouse Neurological Rehabilitation Center, Kingsley, MI, United States
c Department of Occupational Therapy, Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, United States
d Department of Pediatric Newborn Medicine, Brigham and Women's Infant Hospital, Boston, MA, United States

Abstract
Objective. To investigate changes in head lag across postmenstrual age and define associations between head lag and (1) perinatal exposures and (2) neurodevelopment. METHOD. Sixty-four infants born ≤30 wk gestation had head lag assessed before and at term-equivalent age. Neurobehavior was assessed at term age. At 2 yr, neurodevelopmental testing was conducted. RESULTS. Head lag decreased with advancing postmenstrual age, but 58% (n = 37) of infants continued to demonstrate head lag at term. Head lag was associated with longer stay in the neonatal intensive care unit (p =.009), inotrope use (p =.04), sepsis (p =.02), longer endotracheal intubation (p =.01), and cerebral injury (p =.006). Head lag was related to alterations in early neurobehavior (p <.03), but no associations with neurodevelopment were found at 2 yr. CONCLUSION. Head lag was related to medical factors and early neurobehavior, but it may not be a good predictor of outcome when used in isolation.

Document Type: Review
Source: Scopus
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Pursley, A.J.a , Saunders, G.H.b 
Knowledge, attitudes, behaviors, and noise exposure of baristas
(2016) International Journal of Audiology, 55 (3), pp. 184-188. 

DOI: 10.3109/14992027.2015.1124295

a Program in Audiology and Communication Sciences, Washington University, School of Medicine, 660 S. Euclid Ave., St. Louis, MO, United States
b National Center for Rehabilitative Auditory Research, Portland VA Medical Center, Portland, United States

Abstract
To examine the daily noise exposure of baristas working in cafes, and to measure their knowledge, attitudes, and behaviors regarding hearing conservation and perceptions of noise in their work environment. Design: Fifteen baristas from six cafes in Portland completed the Knowledge, Attitudes and Behaviors questionnaire, a sound disturbance survey, and a structured interview to document perceptions of noise in the work environment. To measure daily noise exposure, a subset of eight participants wore a personal dosimeter for three different work shifts. Study sample: A total of 11 females and four males, aged between 19 and 36 years old (mean: 26.3, SD: 4.6) recruited from independently owned cafes in the Portland metro area. Results: Dosimetry measurements revealed Leq measurements between 71 and 83 dBA, with noise doses ranging from 4% to 74%, indicating that baristas are not exposed to sound levels above the regulatory criterion. Questionnaire results indicated that baristas have low awareness about the hazards of noise, are not opposed to hearing conservation, and rarely use hearing protection when engaged in noisy activities. Conclusions: Baristas here lacked the pertinent education and motivation to commit to invaluable hearing conservation practices. © 2016 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society.

Author Keywords
cafes;  health belief model;  Hearing conservation;  noise-induced hearing loss;  questionnaires

Document Type: Article
Source: Scopus
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Brightman, D.S.a b , Razafsky, D.a , Potter, C.a , Hodzic, D.a , Chen, S.a c 
Nrl-Cre transgenic mouse mediates loxP recombination in developing rod photoreceptors
(2016) Genesis, . Article in Press. 

DOI: 10.1002/dvg.22918

a Department of Ophthalmology and Visual SciencesWashington University School of MedicineSaint Louis, Missouri
b Molecular Cell Biology Graduate Program, Division of Biology and Biomedical Sciences, Washington University School of MedicineSaint Louis, Missouri
c Department of Developmental BiologyWashington University School of MedicineSaint Louis, Missouri

Abstract
The developing mouse retina is a tractable model for studying neurogenesis and differentiation. Although transgenic Cre mouse lines exist to mediate conditional genetic manipulations in developing mouse retinas, none of them act specifically in early developing rods. For conditional genetic manipulations of developing retinas, a Nrl-Cre mouse line in which the Nrl promoter drives expression of Cre in rod precursors was created. The results showed that Nrl-Cre expression was specific to the retina where it drives rod-specific recombination with a temporal pattern similar to endogenous Nrl expression during retinal development. This Nrl-Cre transgene does not negatively impact retinal structure and function. Taken together, the data suggested that the Nrl-Cre mouse line was a valuable tool to drive Cre-mediated recombination specifically in developing rods. © 2016 Wiley Periodicals, Inc.

Author Keywords
Differentiation;  Neuronal development;  Retina-specific Cre;  Transgenic

Document Type: Article in Press
Source: Scopus
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Dadey, D.Y.a e , Kapoor, V.a , Khudanyan, A.a , Urano, F.b c , Kim, A.H.d g h , Thotala, D.a g , Hallahan, D.E.a f g h 
The ATF6 pathway of the ER stress response contributes to enhanced viability in glioblastoma
(2016) Oncotarget, 7 (2), pp. 2080-2092. 

DOI: 10.18632/oncotarget.6712

a Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
c Department of Pathology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
e Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, United States
f Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
g Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States
h Hope Center, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Therapeutic resistance is a major barrier to improvement of outcomes for patients with glioblastoma. The endoplasmic reticulum stress response (ERSR) has been identified as a contributor to chemoresistance in glioblastoma; however the contributions of the ERSR to radioresistance have not been characterized. In this study we found that radiation can induce ER stress and downstream signaling associated with the ERSR. Induction of ER stress appears to be linked to changes in ROS balance secondary to irradiation. Furthermore, we observed global induction of genes downstream of the ERSR in irradiated glioblastoma. Knockdown of ATF6, a regulator of the ERSR, was sufficient to enhance radiation induced cell death. Also, we found that activation of ATF6 contributes to the radiation-induced upregulation of glucose regulated protein 78 (GRP78) and NOTCH1. Our results reveal ATF6 as a potential therapeutic target to enhance the efficacy of radiation therapy.

Author Keywords
ATF6;  ER-stress;  Glioblastoma;  GRP78;  Radioresistance

Document Type: Article
Source: Scopus
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Yan, Y., Wood, M.D., Hunter, D.A., Ee, X., Mackinnon, S.E., Moore, A.M.
The Effect of Short Nerve Grafts in Series on Axonal Regeneration Across Isografts or Acellular Nerve Allografts
(2016) Journal of Hand Surgery, . Article in Press. 

DOI: 10.1016/j.jhsa.2016.01.009

Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, MO

Abstract
Purpose: To evaluate the regenerative effect of the additional suture line when using either isografts (ISOs) or acellular nerve allografts (ANAs) placed end-to-end to span a short gap in a rat model. Methods: Rat sciatic nerves were transected and repaired with 2-cm nerve grafts (ISO or ANA). The grafts were 2 cm in length or a 1-cm segment was connected end-to-end to a 1-cm segment to yield a 2-cm length. At 8 weeks, extensor digitorum longus (EDL) muscle force and mass were measured. Nerves were harvested for histomorphometry. In a separate parallel study, the nerves were harvested 2 weeks following graft implantation to assess gene expression changes. Results: All grafts demonstrated regeneration across the 2-cm segment(s). The additional suture line did not result in statistical differences in the number of myelinated nerve fibers that reached the distal nerve. However, when the graft types were compared, there was a significant decrease in nerve fibers in the ANA groups. The EDL muscle mass was significantly greater by using nerve ISOs compared with ANAs, regardless of an additional suture line, but there were no statistical differences noted in EDL muscle force. Gene expression analysis did not differ owing to an additional suture line. Conclusions: Minimal axonal loss and no functional deficits were identified with an additional suture line in this rodent short nerve gap model. Clinical relevance: Placing nerve grafts in series is a viable option for treating short nerve gaps; however, the use of autografts remains preferable over the use of ANAs. © 2016 American Society for Surgery of the Hand.

Author Keywords
Coaptation site;  Nerve regeneration;  Peripheral nerve;  Processed nerve allograft;  Suture line

Document Type: Article in Press
Source: Scopus
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Scherrer, J.F.a b c , Salas, J.a b , Copeland, L.A.d e f , Stock, E.M.d e , Schneider, F.D.a , Sullivan, M.g , Bucholz, K.K.h , Burroughs, T.c , Lustman, P.J.h i 
Increased Risk of Depression Recurrence After Initiation of Prescription Opioids in Noncancer Pain Patients
(2016) Journal of Pain, . Article in Press. 

DOI: 10.1016/j.jpain.2015.12.012

a Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, Missouri
b Research Service, Harry S. Truman Veterans Administration Medical Center, Columbia, Missouri
c Saint Louis University Center for Outcomes Research, St. Louis, Missouri
d Center for Applied Health Research, Baylor Scott and White Health, and Central Texas Veterans Health Care System, Temple, Texas
e Department of Medicine, Texas A and M Health Science Center, Bryan, Texas
f Department of Psychiatry, UT Health Science Center, San Antonio, Texas
g Department of Psychiatry and Behavioral Health, University of Washington School of Medicine, Seattle, Washington
h Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
i Mental Health Service, The Bell Street Clinic, VA St. Louis Health Care System - John Cochran Division, St. Louis, Missouri

Abstract
Several studies have shown that chronic opioid analgesic use is associated with increased risk of new-onset depression. It is not known if patients with remitted depression are at increased risk of relapse after exposure to opioid analgesics. A retrospective cohort design using patient data from the Veterans Health Administration (VHA; n = 5,400), and Baylor Scott & White Health (BSWH; n = 842) was performed with an observation period in the VHA from 2002 to 2012 and in the BSWH from 2003 to 2012. Eligible patients had a diagnosis of depression at baseline and experienced a period of remission. Risk of depression recurrence was modeled in patients that either started taking an opioid or continued without opioid prescriptions before or during remission. Cox proportional hazard models were used to measure the association between opioid use and depression recurrence controlling for pain, and other confounders. Patients exposed to an opioid compared with those unexposed had a significantly greater risk of depression recurrence in both patient populations (VHA: hazard ratio [HR] = 2.17, 95% confidence interval [CI], 2.01-2.34; BSWH: HR = 1.77; 95% CI, 1.42-2.21). These results suggest opioid use doubles the risk of depression recurrence even after controlling for pain, psychiatric disorders, and opioid misuse. Further work is needed to determine if risk increases with duration of use. Repeated screening for depression after opioid initiation may be warranted. Perspective: In 2 large patient cohorts with large differences in demographic characteristics and comorbidity, patients with remitted depression who were exposed to opioid analgesics were 77% to 117% more likely to experience a recurrence of depression than those who remained opioid -free. Routine, not just at initiation of treatment, screening for depression is warranted. © 2016 American Pain Society.

Author Keywords
Depression recurrence;  Epidemiology;  Opioids;  Pain;  Retrospective

Document Type: Article in Press
Source: Scopus
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Eichen, D.M.a f , Kass, A.E.b , Fitzsimmons-Craft, E.E.a , Gibbs, E.c , Trockel, M.d , Barr Taylor, C.d e , Wilfley, D.E.a 
Non-suicidal self-injury and suicidal ideation in relation to eating and general psychopathology among college-age women
(2016) Psychiatry Research, . Article in Press. 

DOI: 10.1016/j.psychres.2015.11.046

a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
b Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
c PGSP-Stanford PsyD Consortium, Palo Alto, CA, USA
d Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA
e Center for M-Health, Palo Alto University, Palo Alto, CA, USA
f Department of Pediatrics, University of California-San Diego, San Diego, CA, USA

Abstract
Non-suicidal self-injury (NSSI) and suicidal ideation are potent risk factors for suicide and are associated with general and eating disorder-specific psychopathology. Limited research has examined the effects of combined NSSI+suicidal ideation thus concurrent examination is needed to understand potential differential effects on psychopathology. College-aged women (N=508) completed self-report measures of NSSI, suicidal ideation, general psychopathology, and Eating Disorder-specific psychopathology. MANOVAs determined whether the NSSI/SI status groups differed on general and eating disorder pathology measures as a set. Significant MANOVAs were followed up with univariate ANOVAs and posthoc tests. Thirteen women endorsed NSSI+Suicidal Ideation, 70 endorsed NSSI-only, 25 endorsed Suicidal Ideation-only, and 400 endorsed no NSSI/Suicidal Ideation. Both general and eating disorder-specific psychopathology differed across groups. NSSI+Suicidal Ideation and Suicidal Ideation-only groups typically endorsed higher general psychopathology than the no NSSI/Suicidal Ideation and NSSI-only groups. Regarding eating disorder pathology, the NSSI+Suicidal Ideation group was more pathological than no NSSI/Suicidal Ideation and NSSI-only, except on the weight concerns scale, where NSSI+Suicidal Ideation only differed from no NSSI/Suicidal Ideation. The NSSI+Suicidal Ideation group was only greater than Suicidal Ideation-only on measures of depression and eating concern. Results highlight the importance of screening for both NSSI and suicidal ideation, especially for individuals with eating disorder symptoms. Likewise, screening for eating disorder pathology may be beneficial for individuals presenting with NSSI and suicidal ideation. © 2015.

Author Keywords
Comorbidity;  Depression;  Eating disorders;  Suicide

Document Type: Article in Press
Source: Scopus
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Ramkumar, V.a , Borse, V.a , Ghosh, S.a , Kaur, T.c , Sheehan, K.b , Sheth, S.a , Dhukhwa, A.a , Tupal, S.a , Mukherjea, D.b , Rybak, L.P.b 
Role of adenosine receptors in auditory functions
(2015) Adenosine Signaling Mechanisms: Pharmacology, Functions and Therapeutic Aspects, pp. 183-192. 

a Department of Pharmacology, Springfield, IL, United States
b Department of Surgery (Otolaryngology), Southern Illinois University School of Medicine, Springfield, IL, United States
c Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Following the initial characterization of adenosine receptors in the cochlea, it was shown that activation of these receptors increased the activity of antioxidant enzymes in the cochlea. The cochlea also expresses various ATP hydrolytic enzymes responsible for the synthesis of adenosine, along with equilibrative and concentrative transporters. Adenosine receptors show distinct distribution patterns in the cochlea. Their ability to increase antioxidant enzymes, prompted future studies to determine the efficacy of adenosine receptor agonists to treat hearing loss induced by chemotherapeutic agents and noise trauma, conditions linked to the generation of reactive oxygen species. To date, agents that activate the A1 adenosine receptor appear to show efficacy for the treatment of hearing loss in animal studies. It is yet to be shown that these agents are effective for preventing and treating hearing loss in humans. A major problem yet to be addressed is how to administer these drugs for treatment of hearing loss without producing significant side effects. © 2015 by Nova Science Publishers, Inc. All rights reserved.

Document Type: Book Chapter
Source: Scopus

 

February 18, 2016

Zaninotto, L.a , Solmi, M.b , Toffanin, T.b , Veronese, N.c , Cloninger, C.R.d , Correll, C.U.e f
A meta-analysis of temperament and character dimensions in patients with mood disorders: Comparison to healthy controls and unaffected siblings
(2016) Journal of Affective Disorders, 194, pp. 84-97. 

DOI: 10.1016/j.jad.2015.12.077


a Department of Biomedical and Neuro-Motor Sciences, University of Bologna, Viale Carlo Pepoli 5, Bologna, Italy
b Department of Neuroscience, University of Padova, Padova, Italy
c Department of Medicine, Geriatric Section, University of Padova, Padova, Italy
d Washington University, School of Medicine, 660 South Euclid Avenue, St Louis, MO, United States
e Zucker Hillside Hospital, Psychiatry Research, North Shore-Glen OaksNY, United States
f Hofsra North Shore LIJ School of Medicine, Hampstead, NY, United States


Abstract
Background Cloninger's psychobiological model of personality has been extensively applied to subjects affected by mood disorders (MOOD). However, most studies are widely heterogeneous in terms of sample size, methods of assessment, and selection of participants. Methods We conducted a systematic review of literature and a random effects meta-analysis of studies comparing at least two of the following groups: (a) adults with a primary MOOD diagnosis (Bipolar Disorder (BP) or major depressive disorder (MDD)), (b) their unaffected siblings (SIB) or (c) healthy subjects (HS), and reporting quantitative results from the Tridimensional Personality Questionnaire (TPQ) or the Temperament and Character Inventory (TCI). Subgroup, sensitivity and meta-regression analyses were also conducted. Results High Harm Avoidance and low Self-Directedness were consistently associated with MOOD and SIB samples. BP was characterized by higher scores in Novelty Seeking and Self-Transcendence than HS, SIB and MDD. Age seemed to have a negative effect on Novelty Seeking and a positive effect on Harm Avoidance, Cooperativeness and Self-Transcendence. An euthymic mood state was associated with reduced Harm Avoidance, but increased Reward Dependence, Self-Directedness and Cooperativeness. Limitations The quality of the included studies varied and was relatively low. Moreover, publication bias and heterogeneity in the distribution of effect sizes may also have limited our results. Conclusion High Harm Avoidance and Low Self-Directedness may be trait markers for MOOD in general, while high Novelty Seeking and high Self-Transcendence may be specific to BP. Future studies are needed to disentangle the state-trait effect of each personality dimension. © 2016 Elsevier B.V. All rights reserved.


Author Keywords
Bipolar Disorder;  Character;  Depression;  Mood disorders;  State;  Temperament;  Trait


Document Type: Review
Source: Scopus




Kennedy, S.C.a , Tripodi, S.J.a , Pettus-Davis, C.b , Ayers, J.a
Examining Dose–Response Relationships Between Childhood Victimization, Depression, Symptoms of Psychosis, and Substance Misuse for Incarcerated Women
(2016) Women and Criminal Justice, 26 (2), pp. 77-98. 

DOI: 10.1080/08974454.2015.1023486


a College of Social Work, Florida State University, Tallahassee, FL, United States
b George Warren Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States


Abstract
The current study uses the dose–response model to examine the relationships between childhood victimization events and subsequent depression, symptoms of psychosis, and substance misuse in a sample of 230 randomly selected incarcerated women in the United States. Results on the frequency of victimization were mixed. In this sample, both frequency of physical abuse and frequency of sexual abuse significantly predicted current symptoms of psychosis, but only frequency of physical abuse significantly predicted substance misuse. Incarcerated women who experienced multivictimization were 5.7 times as likely to report depression, 4.2 times as likely to report current symptoms of psychosis, and 3.8 times as likely to meet criteria for a substance use disorder. Results indicate that adjusting prison-based interventions to address multivictimization may improve outcomes and reduce recidivism among this population. © 2016, Copyright © Taylor & Francis Group, LLC.


Author Keywords
childhood victimization;  dose–response model;  incarcerated women;  mental health;  substance misuse


Document Type: Article
Source: Scopus




Phatarakijnirund, V.a b , Mumm, S.a b , McAlister, W.H.c , Novack, D.V.b , Wenkert, D.a , Clements, K.L.a , Whyte, M.P.a b
Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9
(2016) Bone, 84, pp. 289-298. 

DOI: 10.1016/j.bone.2015.11.022


a Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO, United States
b Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, United States
c Department of Pediatric Radiology, Mallinckrodt Institute of Radiology at St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Congenital insensitivity to pain (CIP) comprises the rare heritable disorders without peripheral neuropathy that feature inability to feel pain. Fracturing and joint destruction are common complications, but lack detailed studies of mineral and skeletal homeostasis and bone histology. In 2013, discovery of a heterozygous gain-of-function mutation in SCN11A encoding voltage-gated sodium channel 1.9 (Nav1.9) established a distinctive CIP in three unrelated patients who suffered multiple painless fractures, self-inflicted mutilation, chronic diarrhea, and hyperhidrosis.Here, we studied a mother and two children with CIP by physical examination, biochemical testing, radiological imaging including DXA, iliac crest histology, and mutation analysis.She suffered fractures primarily of her lower extremities beginning at age two years, and had Charcot deformity of both ankles and joint hypermobility. Nerve conduction velocity together with electromyography were normal. Her children had recurrent major fractures beginning in early childhood, joint hypermobility, and chronic diarrhea. She had an excoriated external nare, and both children had hypertrophic scars from scratching. Skin collagen studies were normal. Radiographs revealed fractures and deformities. However, lumbar spine and total hip BMD Z-scores, biochemical parameters of mineral and skeletal homeostasis, and iliac crest histology of the mother (after in vivo tetracycline labeling) were normal. Genomic DNA from the children revealed a unique heterozygous missense mutation in exon 23 (c.3904C. &gt;. T, p.Leu1302Phe) of SCN11A that is absent in SNP databases and alters an evolutionarily conserved amino acid.This autosomal dominant CIP reflects the second gain-of-function mutation of SCN11A. Perhaps joint hypermobility is an unreported feature. How mutation of Nav1.9 causes fracturing remains unexplained. Lack of injury awareness is typically offered as the reason, and was supported by our unremarkable biochemical, radiological, and histological findings indicating no skeletal pathobiology. However, low-trauma fracturing in these patients suggests an uncharacterized defect in bone quality. © 2016 Elsevier Inc.


Author Keywords
Charcot arthropathy;  Joint hypermobility;  Mineral homeostasis;  Skeletal homeostasis


Document Type: Article
Source: Scopus




Iyer, N.R.a , Huettner, J.E.b , Butts, J.C.a , Brown, C.R.a , Sakiyama-Elbert, S.E.a
Generation of highly enriched V2a interneurons from mouse embryonic stem cells
(2016) Experimental Neurology, 277, pp. 305-316. 

DOI: 10.1016/j.expneurol.2016.01.011


a Department of Biomedical Engineering, Washington University, Campus Box 1097, One Brookings Drive, St. Louis, MO, United States
b Department of Cell Biology and Physiology, Washington University School of Medicine, Campus Box 8228, 660 South Euclid Avenue, St. Louis, MO, United States


Abstract
Challenges in parsing specific contributions to spinal microcircuit architecture have limited our ability to model and manipulate those networks for improved functional regeneration after injury or disease. While spinal interneurons (INs) have been implicated in driving coordinated locomotor behaviors, they constitute only a small percentage of the spinal cord and are difficult to isolate from primary tissue. In this study, we employed a genetic strategy to obtain large quantities of highly enriched mouse embryonic stem cell (ESC)-derived V2a INs, an excitatory glutamatergic IN population that is defined by expression of the homeodomain protein Chx10 during development. Puromycin N-acetyltransferase expression was driven by the native gene regulatory elements of Chx10 in the transgenic ESC line, resulting in positive selection of V2a INs after induction and treatment with puromycin. Directly after selection, approximately 80% of cells are Chx10+, with 94% Lhx3+; after several weeks, cultures remain free of proliferative cell types and mature into normal glutamatergic neurons as assessed by molecular markers and electrophysiological methods. Functional synapses were observed between selected ESC-derived V2a INs and motor neurons when co-cultured, demonstrating the potential of these cells to form neural networks. While ESC-derived neurons obtained in vitro are not identical to those that develop in the spinal cord, the transgenic ESCs here provide a unique tool to begin studying V2a INs in isolation or for use in in vitro models of spinal microcircuits. © 2016 Elsevier Inc.


Author Keywords
Electrophysiology;  Neuronal differentiation;  Puromycin selection;  Spinal cord injury;  Transcription factor


Document Type: Article
Source: Scopus




Dietz, A.R., Bucelli, R.C., Pestronk, A., Zaidman, C.M.
Nerve ultrasound identifies abnormalities in the posterior interosseous nerve in patients with proximal radial neuropathies
(2016) Muscle and Nerve, 53 (3), pp. 379-383. 

DOI: 10.1002/mus.24778


Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, MO, United States


Abstract
Introduction: The radial nerve and posterior interosseous nerve (PIN) are prone to injury at multiple sites. Electrodiagnostic (EDx) studies may only identify the most proximal lesion. Nerve ultrasound could augment EDx by visualizing additional pathology. Methods: This investigation was a retrospective examination of ultrasound and EDx from 26 patients evaluated for posterior cord/radial/PIN lesions. Results: Eighteen of 26 patients had abnormalities on EDx (15 radial, 2 PIN, 1 posterior cord). Ultrasound identified 15 of 18 (83%) of the EDx abnormalities and provided additional diagnostic information. In 6 of 15 (40%) patients with EDx evidence of radial neuropathy, ultrasound identified both radial nerve enlargement and additional, unsuspected PIN enlargement (53% to 339% enlarged vs. unaffected side). Ultrasound also identified: nerve (dis)continuity at the trauma site (n = 8); and nerve tumor (n = 2; 1 with normal EDx). Conclusion: In radial neuropathy, ultrasound often augments EDx studies and identifies a second lesion in the PIN. Further studies are required to determine the etiology and significance of this additional distal pathology. © 2016 Wiley Periodicals, Inc.


Author Keywords
Double crush syndrome;  Neuropathy;  Posterior interosseous nerve;  Radial nerve;  Ultrasound


Document Type: Article
Source: Scopus




Bonner, M.F.a , Price, A.R.a , Peelle, J.E.b , Grossman, M.a
Semantics of the visual environment encoded in parahippocampal cortex
(2016) Journal of Cognitive Neuroscience, 28 (3), pp. 361-378. 

DOI: 10.1162/jocn_a_00908


a University of Pennsylvania, United States
b Washington University in St. Louis, United States


Abstract
Semantic representations capture the statistics of experience and store this information in memory. A fundamental component of this memory system is knowledge of the visual environment, including knowledge of objects and their associations. Visual semantic information underlies a range of behaviors, from perceptual categorization to cognitive processes such as language and reasoning. Here we examine the neuroanatomic system that encodes visual semantics. Across three experiments, we found converging evidence indicating that knowledge of verbally mediated visual concepts relies on information encoded in a region of the ventralmedial temporal lobe centered on parahippocampal cortex. In an fMRI study, this region was strongly engaged by the processing of concepts relying on visual knowledge but not by concepts relying on other sensory modalities. In a study of patients with the semantic variant of primary progressive aphasia (semantic dementia), atrophy that encompassed this region was associated with a specific impairment in verbally mediated visual semantic knowledge. Finally, in a structural study of healthy adults from the fMRI experiment, gray matter density in this region related to individual variability in the processing of visual concepts. The anatomic location of these findings aligns with recent work linking the ventral-medial temporal lobe with high-level visual representation, contextual associations, and reasoning through imagination. Together, this work suggests a critical role for parahippocampal cortex in linking the visual environment with knowledge systems in the human brain. © 2016 Massachusetts Institute of Technology.


Document Type: Article
Source: Scopus




Wong, M.a , Roper, S.N.b
Genetic animal models of malformations of cortical development and epilepsy
(2016) Journal of Neuroscience Methods, 260, pp. 73-82. 

DOI: 10.1016/j.jneumeth.2015.04.007


a Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurosurgery, University of Florida, Gainesville, FL, United States


Abstract
Malformations of cortical development constitute a variety of pathological brain abnormalities that commonly cause severe, medically-refractory epilepsy, including focal lesions, such as focal cortical dysplasia, heterotopias, and tubers of tuberous sclerosis complex, and diffuse malformations, such as lissencephaly. Although some cortical malformations result from environmental insults during cortical development in utero, genetic factors are increasingly recognized as primary pathogenic factors across the entire spectrum of malformations. Genes implicated in causing different cortical malformations are involved in a variety of physiological functions, but many are focused on regulation of cell proliferation, differentiation, and neuronal migration. Advances in molecular genetic methods have allowed the engineering of increasingly sophisticated animal models of cortical malformations and associated epilepsy. These animal models have identified some common mechanistic themes shared by a number of different cortical malformations, but also revealed the diversity and complexity of cellular and molecular mechanisms that lead to the development of the pathological lesions and resulting epileptogenesis. © 2015 Elsevier B.V..


Author Keywords
Focal cortical dysplasia;  Heterotopia;  Lissencephaly;  Mice;  Seizure;  Tuberous sclerosis


Document Type: Review
Source: Scopus




Lam, H.T., Graber, M.C., Gentry, K.A., Bieschke, J.
Stabilization of α-Synuclein Fibril Clusters Prevents Fragmentation and Reduces Seeding Activity and Toxicity
(2016) Biochemistry, 55 (4), pp. 675-685. 

DOI: 10.1021/acs.biochem.5b01168


Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, MO, United States


Abstract
Protein misfolding results in the accumulation of aggregated β-sheet-rich structures in Parkinson's disease (PD) and Alzheimer's disease. The toxic oligomer hypothesis stipulates that prefibrillar assemblies, such as soluble oligomers or protofibrils, are responsible for the poor prognosis of these diseases. Previous studies demonstrated that a small molecule related to the natural compound orcein, O4, directly binds to amyloid-β fibrils and stabilizes them, accelerating the formation of end-stage mature fibrils. Here we demonstrate a similar phenomenon during O4 treatment of α-synuclein (αsyn) aggregates, the protein responsible for PD pathology. While the drug did not change the kinetics of aggregate formation as measured by the amyloidophilic dye thioflavin T, O4 depleted αsyn oligomers and promoted the formation of sodium dodecyl sulfate and proteinase K resistant aggregates consisting of large fibril clusters. These fibril clusters exhibited reduced toxicity to human neuronal model cells and reduced seeding activity in vitro. The effectiveness of O4 decreased when it was added at later points in the αsyn aggregation pathway, which suggests that the incorporation of O4 into fibril assemblies stabilizes them against chemical, enzymatic, and mechanic degradation. These findings suggest that small molecules, which stabilize amyloid fibrils, can prevent fibril fragmentation and seeding and consequently prevent prion-like replication of misfolded αsyn. Inhibiting prion replication by fibril stabilization could thus be a therapeutic strategy for PD. © 2016 American Chemical Society.


Document Type: Article
Source: Scopus




Piccirillo, J.F.
Transcranial Magnetic Stimulation for Chronic Tinnitus
(2016) JAMA, 315 (5), pp. 506-507. 

DOI: 10.1001/jama.2016.0075


Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine, St Louis, Missouri; and Editor, JAMA Otolaryngology-Head & Neck Surgery


Document Type: Note
Source: Scopus




Aschenbrenner, A.J.a , Balota, D.A.a b , Gordon, B.A.c , Ratcliff, R.d , Morris, J.C.b
A diffusion model analysis of episodic recognition in preclinical individuals with a family history for Alzheimer's disease: The adult children study
(2016) Neuropsychology, 30 (2), pp. 225-238. 

DOI: 10.1037/neu0000222


a Department of Psychology, Washington University in St. Louis, United States
b Department of Neurology, Washington University in St. Louis, United States
c Department of Radiology, Washington University in St. Louis, United States
d Department of Psychology, The Ohio State University, United States


Abstract
Objective: A family history of Alzheimer's disease (AD) increases the risk of developing AD and can influence the accumulation of well-established AD biomarkers. There is some evidence that family history can influence episodic memory performance even in cognitively normal individuals. We attempted to replicate the effect of family history on episodic memory and used a specific computational model of binary decision making (the diffusion model) to understand precisely how family history influences cognition. Finally, we assessed the sensitivity of model parameters to family history controlling for standard neuropsychological test performance. Method: Across 2 experiments, cognitively healthy participants from the Adult Children Study completed an episodic recognition test consisting of high- and low-frequency words. The diffusion model was applied to decompose accuracy and reaction time (RT) into latent parameters which were analyzed as a function of family history. Results: In both experiments, individuals with a family history of AD exhibited lower recognition accuracy and this occurred in the absence of an apolipoprotein E (APOE) ε4 allele. The diffusion model revealed this difference was due to changes in the quality of information accumulation (the drift rate) and not differences in response caution or other model parameters. This difference remained after controlling for several standard neuropsychological tests. Conclusions: These results confirm that the presence of a family history of AD confers a subtle cognitive deficit in episodic memory as reflected by decreased drift rate that cannot be attributed to APOE. This measure may serve as a novel cognitive marker of preclinical AD. © 2015 American Psychological Association.


Author Keywords
Alzheimer's disease;  Diffusion model;  Family history;  Memory


Document Type: Article
Source: Scopus




Fitzsimmons-Craft, E.E.a , Ciao, A.C.b , Accurso, E.C.c
A naturalistic examination of social comparisons and disordered eating thoughts, urges, and behaviors in college women
(2016) International Journal of Eating Disorders, 49 (2), pp. 143-152. 

DOI: 10.1002/eat.22486


a Department of Psychiatry, Washington University, School of Medicine, Campus Box 8134, 660 S. Euclid Ave., St. Louis, MO, United States
b Department of Psychology, Western Washington University, Bellingham, WA, United States
c Department of Psychiatry, University of California, San Francisco, San Francisco, CA, United States


Abstract
Objective We examined the effects of body, eating, and exercise social comparisons on prospective disordered eating thoughts and urges (i.e., restriction thoughts, exercise thoughts, vomiting thoughts, binge eating urges) and behaviors (i.e., restriction attempts, exercising for weight/shape reasons, vomiting, binge eating) among college women using ecological momentary assessment (EMA). Method Participants were 232 college women who completed a 2-week EMA protocol, in which they used their personal electronic devices to answer questions three times per day. Generalized estimating equation models were used to assess body, eating, and exercise comparisons as predictors of disordered eating thoughts, urges, and behaviors at the next report, adjusting for body dissatisfaction, negative affect, and the disordered eating thought/urge/behavior at the prior report, as well as body mass index. Results Body comparisons prospectively predicted more intense levels of certain disordered eating thoughts (i.e., thoughts about restriction and exercise). Eating comparisons prospectively predicted an increased likelihood of subsequent engagement in all disordered eating behaviors examined except vomiting. Exercise comparisons prospectively predicted less-intense thoughts about exercise and an increased likelihood of subsequent vomiting. Discussion Social comparisons are associated with later disordered eating thoughts and behaviors in the natural environment and may need to be specifically targeted in eating disorder prevention and intervention efforts. Targeting body comparisons may be helpful in terms of reducing disordered eating thoughts, but eating and exercise comparisons are also important and may need to be addressed in order to decrease engagement in actual disordered eating behaviors. © 2015 Wiley Periodicals, Inc.


Author Keywords
college students;  disordered eating;  eating disorder;  ecological momentary assessment;  social comparison


Document Type: Article
Source: Scopus




Friess, S.H.
Comparing Apples and Oranges: Seizure Prophylaxis in Pediatric Traumatic Brain Injury
(2016) Pediatric Critical Care Medicine, 17 (2), pp. 173-174. 

DOI: 10.1097/PCC.0000000000000593


Department of Pediatrics, Washington University, St. Louis School of Medicine, St. Louis, MO, United States


Author Keywords
comparative effectiveness research;  levetiracetam;  pediatrics;  seizure prophylaxis;  traumatic brain injury


Document Type: Editorial
Source: Scopus




Kang, P.a , Raya, A.a , Zipfel, G.J.b , Dhar, R.a
Factors Associated with Acute and Chronic Hydrocephalus in Nonaneurysmal Subarachnoid Hemorrhage
(2016) Neurocritical Care, 24 (1), pp. 104-109. 

DOI: 10.1007/s12028-015-0152-7


a Neurocritical Care Section, Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8111, St. Louis, MO, United States
b Department of Neurological Surgery, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8057, St. Louis, MO, United States


Abstract
Background: Hydrocephalus requiring external ventricular drain (EVD) or shunt placement commonly complicates aneurysmal subarachnoid hemorrhage (SAH), but its frequency is not as well known for nonaneurysmal SAH (NA-SAH). Those with diffuse bleeding may have greater risk of hydrocephalus compared to those with a perimesencephalic pattern. We evaluated the frequency of hydrocephalus in NA-SAH and whether imaging factors could predict the need for EVD and shunting. Methods: We collected admission clinical and imaging variables for 105 NA-SAH patients, including bicaudate index (BI), Hijdra sum score (HSS), intraventricular hemorrhage (IVH) score, modified Fisher scale (mFS), and bleeding pattern. Hydrocephalus was categorized as acute (need for EVD) or chronic (shunt). We applied logistic regression to determine whether hydrocephalus risk was independently related to bleeding pattern or mediated through blood volume or ventriculomegaly. Results: Acute hydrocephalus was seen in 26 (25 %) patients but was more common with diffuse (15/28, 54 %) versus perimesencephalic (10/59, 17 %, p < 0.001) bleeding. Patients developing acute hydrocephalus had worse clinical grade and higher BI, HSS, and IVH scores. Adjusting the relationship between hydrocephalus and diffuse bleeding for HSS (but not BI) nullified this association. Nine (35 %) patients requiring EVD eventually required shunting for chronic hydrocephalus, which was associated with greater blood burden but not poor clinical grade. Conclusion: Acute hydrocephalus occurs in one-quarter of NA-SAH patients. The greater risk in diffuse bleeding appears to be mediated by greater cisternal blood volume but not by greater ventriculomegaly. Imaging characteristics may aid in anticipatory management of hydrocephalus in NA-SAH. © 2015, Springer Science+Business Media New York.


Author Keywords
Angiogram negative;  External ventricular drain;  Hydrocephalus;  Nonaneurysmal;  Subarachnoid hemorrhage;  Ventriculoperitoneal shunt


Document Type: Article
Source: Scopus




Nicol, G.a , Worsham, E.b , Haire-Joshu, D.c , Duncan, A.a d , Schweiger, J.a , Yingling, M.a , Lenze, E.a
Getting to More Effective Weight Management in Antipsychotic-Treated Youth: A Survey of Barriers and Preferences
(2016) Childhood Obesity, 12 (1), pp. 70-76. 

DOI: 10.1089/chi.2015.0076


a Healthy Mind Lab., Department of Psychiatry, Washington University School of Medicine in St. Louis, Campus Box 8134, 660 South Euclid Avenue, St. Louis, MO, United States
b Department of Psychiatry, Forensic Institute, University of Florida, Gainesville, FL, United States
c George Warren Brown School of Social Work, Center for Diabetes Translation Research, Center for Obesity Prevention and Policy Research, Washington University, St. Louis, MO, United States
d Department of Public Health, George Warren Brown School of Social Work, Washington University, St. Louis, MO, United States


Abstract
Background: Mentally ill youth are at risk for developing obesity, especially when they require antipsychotic treatment; moreover, they may face unique challenges in adhering to behavioral weight loss interventions. The aims of this project were to characterize the challenges families of youth with psychiatric disorders face when engaging in weight loss treatment and to gather information on attitudes and preferences for weight management interventions in this population. Methods: We devised a telephone survey to evaluate caregiver-perceived barriers/challenges to and preferences for behavioral weight loss treatment in overweight or obese mentally ill youth ages 6-18 treated with an antipsychotic agent in an outpatient setting. Results: A total of 26 parents or primary caregivers completed the survey. The most commonly cited barriers to participation in physical activity (PA) and maintaining a healthy diet were child's dislike of PA and child's preference for energy-dense foods, respectively, which were impacted by psychiatric symptoms. Preferences for weight loss treatment included individualized, prescribed meal plans and shopping lists, and exercise support/demonstration, with a preference for Internet or cell phone applications to help with monitoring food intake and exercise. Conclusions: These results suggest that targets for obesity treatment in this population include individualized, specific support that takes into account the child's motivation, which is effected by psychiatric symptoms. Tools for providing support may include the use of telehealth visits and mobile device applications for self-monitoring. © Copyright 2016, Mary Ann Liebert, Inc.


Document Type: Article
Source: Scopus




Shen, S.Q.a , Myers, C.A.a , Hughes, A.E.O.a , Byrne, L.C.b , Flannery, J.G.b , Corbo, J.C.a
Massively parallel cis-regulatory analysis in the mammalian central nervous system
(2016) Genome Research, 26 (2), pp. 238-255. 

DOI: 10.1101/gr.193789.115


a Department of Pathology and Immunology, Washington University, School of Medicine, St. Louis, MO, United States
b Helen Wills Neuroscience Institute, University of California, Berkeley, CA, United States


Abstract
Cis-regulatory elements (CREs, e.g., promoters and enhancers) regulate gene expression, and variants within CREs can modulate disease risk. Next-generation sequencing has enabled the rapid generation of genomic data that predict the locations of CREs, but a bottleneck lies in functionally interpreting these data. To address this issue, massively parallel reporter assays (MPRAs) have emerged, in which barcoded reporter libraries are introduced into cells, and the resulting barcoded transcripts are quantified by next-generation sequencing. Thus far, MPRAs have been largely restricted to assaying short CREs in a limited repertoire of cultured cell types. Here, we present two advances that extend the biological relevance and applicability of MPRAs. First, we adapt exome capture technology to instead capture candidate CREs, thereby tiling across the targeted regions and markedly increasing the length of CREs that can be readily assayed. Second, we package the library into adeno-associated virus (AAV), thereby allowing delivery to target organs in vivo. As a proof of concept, we introduce a capture library of about 46,000 constructs, corresponding to roughly 3500 DNase I hypersensitive (DHS) sites, into the mouse retina by ex vivo plasmid electroporation and into the mouse cerebral cortex by in vivoAAV injection. We demonstrate tissue-specific cis-regulatory activity of DHSs and provide examples of high-resolution truncation mutation analysis for multiplex parsing of CREs. Our approach should enable massively parallel functional analysis of a wide range of CREs in any organ or species that can be infected by AAV, such as nonhuman primates and human stem cellderived organoids. © 2016 Shen et al.


Document Type: Article
Source: Scopus




Dori, A.a b c , Lopate, G.b , Choksi, R.b , Pestronk, A.b
Myelinated and unmyelinated endoneurial axon quantitation and clinical correlation
(2016) Muscle and Nerve, 53 (2), pp. 198-204. 

DOI: 10.1002/mus.24740


a Department of Neurology, Talpiot medical leadership program, Chaim Sheba Medical Center, Tel HaShomer, Israel
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Joseph Sagol neuroscience center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel


Abstract
Introduction: Different disease patterns result from loss of myelinated and unmyelinated axons, but quantitation to define their loss has been difficult. Methods: We measured large and small endoneurial axons in axonal neuropathies by staining them with peripherin and comparing their area to that of nonmyelinating Schwann cells stained with neural cell adhesion molecule (NCAM). Results: Loss of myelinated and unmyelinated axons was typically proportional, with predominant myelinated or unmyelinated axon loss in a few patients. Myelinated axon loss was associated with loss of distal vibration sense and sensory potentials (P<0.0001) and was selective in patients with bariatric and bowel resection surgery (P<0.001). Unmyelinated axon measurements correlated with skin (ankle P=0.01; thigh P=0.02) and vascular (nerve P<0.0001; muscle P=0.01) innervation. Conclusions: Myelinated and unmyelinated axons can be quantitated by comparing areas of axons and nonmyelinating Schwann cells. Clinical features correlate with myelinated axon loss, and unmyelinated axon loss correlates with skin and vascular denervation. © 2016 Wiley Periodicals, Inc.


Author Keywords
Myelinated axons;  Neuropathy;  Sural nerve biopsy;  Unmyelinated axons;  Vascular innervation


Document Type: Article
Source: Scopus




Turney, S.G.a , Ahmed, M.c , Chandrasekar, I.c f , Wysolmerski, R.B.d , Goeckeler, Z.M.e , Rioux, R.M.b f g , Whitesides, G.M.b , Bridgman, P.C.c
Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance
(2016) Molecular Biology of the Cell, 27 (3), pp. 500-517. 

DOI: 10.1091/mbc.E15-09-0636


a Center for Brain Science, Department of Molecular and Cellular Biology, United States
b Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, United States
c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, WV, United States
e Brooke Army Medical Center, Ft. Sam Houston, TX, United States
f Sanford Children's Health Research Center, Sanford Research, Sioux Falls, SD, United States
g Department of Chemical Engineering, Pennsylvania State UniversityPA, United States


Abstract
Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- And IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion-cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MIIdependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation. © 2016 Turney et al.


Document Type: Article
Source: Scopus




Deshields, T.a , Kracen, A.a , Nanna, S.b , Kimbro, L.c
Psychosocial staffing at National Comprehensive Cancer Network member institutions: Data from leading cancer centers
(2016) Psycho-Oncology, 25 (2), pp. 164-169. 

DOI: 10.1002/pon.3826


a Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO, United States
b American University of the Caribbean School of Medicine, Cupecoy St. Maarten, Netherlands
c National Comprehensive Cancer Network, Fort Washington, PA, United States


Abstract
Objective The National Comprehensive Cancer Network (NCCN) is comprised of 25 National Cancer Institute-designated cancer centers and arguably could thus set the standard for optimal psychosocial staffing for cancer centers; therefore, information was sought from NCCN Member Institutions about their current staffing for psychosocial services. These findings are put into perspective given the limited existing literature and consensus reports. Methods The NCCN Best Practices Committee surveyed member institutions about their staffing for psychosocial services. The survey was administered electronically in the winter of 2012. Results The survey was completed by 20 cancer centers. Across institutions, case managers and mental health therapists, typically social workers, were utilized most frequently to provide psychosocial services (67% of full-time-equivalents (FTEs)), with other psychosocial professionals also represented but less consistently. Most psychosocial services are institutionally funded (ranging from 64 to 100%), although additional sources of support include fee for service and grant funding. Training of psychosocial providers is unevenly distributed across responding sites, ranging from 92% of institutions having training programs for psychiatrists to 36% having training programs for mental health therapists. Conclusions There was variability among the institutions in terms of patient volume, psychosocial services provided, and psychosocial staff employed. As accreditation standards are implemented that provide impetus for psychosocial services in oncology, it is hoped that greater clarity will develop concerning staffing for psychosocial services and uptake of these services by patients with cancer. Copyright © 2015 John Wiley & Sons, Ltd.


Document Type: Article
Source: Scopus




Miller, J.D.a , Lynam, D.R.b , McCain, J.L.a , Few, L.R.c , Crego, C.d , Widiger, T.A.d , Campbell, W.K.a
Thinking structurally about narcissism: An examination of the five-factor narcissism inventory and its components
(2016) Journal of Personality Disorders, 30 (1), pp. 1-18. 

DOI: 10.1521/pedi_2015_29_177


a University of Georgia, United States
b Purdue University, United States
c Washington University School of Medicine, United States
d University of Kentucky, United States


Abstract
The Five-Factor Narcissism Inventory (FFNI) is a self-report measure of the traits linked to grandiose and vulnerable narcissism, as well as narcissistic personality disorder (NPD), from a five-factor model perspective (FFM). In the current studies, the factor structure of the FFNI was explored and the results supported the extraction of three factors: Antagonism (e.g., Arrogance), Neuroticism (e.g., Need for Admiration), and Agentic Extraversion (e.g., Authoritativeness). In Study 2, the FFNI factors manifested convergent validity with their corresponding Big Five domains and diverging relations with measures of grandiose and vulnerable narcissism, NPD, and selfesteem. Ultimately, the FFNI factors help explicate the differences between various expressions of narcissism such that all are related to Antagonism but differ with regard to Neuroticism (relevant to vulnerable narcissism and NPD) and Agentic Extraversion (relevant to grandiose narcissism and NPD). The results also highlight the complex relation between self-esteem and the traits that comprise narcissism measures. © 2016 The Guilford Press.


Document Type: Article
Source: Scopus




McDermott, K.B.a , Wooldridge, C.L.b , Rice, H.J.a , Berg, J.J.a , Szpunar, K.K.c
Visual perspective in remembering and episodic future thought
(2016) Quarterly Journal of Experimental Psychology, 69 (2), pp. 243-253. 

DOI: 10.1080/17470218.2015.1067237


a Department of Psychology, Washington University in St. Louis, St Louis, MO, United States
b Department of Psychology, Washburn University, Topeka, KS, United States
c Department of Psychology, University of Illinois at Chicago, Chicago, IL, United States


Abstract
According to the constructive episodic simulation hypothesis, remembering and episodic future thinking are supported by a common set of constructive processes. In the present study, we directly addressed this assertion in the context of third-person perspectives that arise during remembering and episodic future thought. Specifically, we examined the frequency with which participants remembered past events or imagined future events from third-person perspectives. We also examined the different viewpoints from which third-person perspective events were remembered or imagined. Although future events were somewhat more likely to be imagined from a third-person perspective, the spatial viewpoint distributions of third-person perspectives characterizing remembered and imagined events were highly similar. These results suggest that a similar constructive mechanism may be at work when people remember events from a perspective that could not have been experienced in the past and when they imagine events from a perspective that could not be experienced in the future. The findings are discussed in terms of their consistency with—and as extensions of—the constructive episodic simulation hypothesis. © 2015 The Experimental Psychology Society.


Author Keywords
Autobiographical memory;  Episodic future thought;  Mental time travel;  Simulation;  Visual perspective


Document Type: Article
Source: Scopus




Randerath, J.a b c , Frey, S.H.c d
Diagnostics and training of affordance perception in healthy young adults-implications for post-stroke neurorehabilitation
(2016) Frontiers in Human Neuroscience, 9 (JAN2016), art. no. 674, . 

DOI: 10.3389/fnhum.2015.00674


a Department of Psychology, University of Konstanz, Konstanz, Germany
b Lurija Institute for Rehabilitation Science and Health Research, Kliniken Schmieder, Allensbach, Germany
c Department of Psychological Sciences, University of Missouri, Columbia, MO, United States
d Department of Neurology and Department of Psychological and Brain Sciences, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Affordance perception is critical to adaptive behavior. It comprises the ability to evaluate whether the environment and the actor’s capabilities enable particular actions. It remains unclear how brain damage and its behavioral sequela impact this ability. Two affordance based judgment tasks were applied in healthy young adults that were adapted for prospective diagnostic purposes in patients. In addition to the commonly analyzed error-rate we included response times and accuracy measures based on a detection theory approach. Moreover, a manipulation was added intended to determine the effectiveness of feedback-based learning. We further applied control tasks that consider whether errors in affordance perception can be explained by errors in perception. Participants responded yes or no to decide prospectively if a given setting would afford a particular action. In study1, 27 participants judged whether their hand would fit through a given aperture (adapted from Ishak et al., 2008). In study2, 19 participants judged whether objects are reachable [adapted from Gabbard et al. (2005)]. For both studies two sessions were administered. In the first session all participants solved the judgment-task without executing the action. In the second session (feedback manipulation), half of the participants were allowed to first judge and then perform the task for each trial (reach forward and touch the object, or fitting the hand into the aperture). Judgments were slowest and errors most frequent for openings or distances close to the individual’s actual physical limits. With more extreme settings accuracy increased and responses became faster. Importantly, we found an advantageous effect of feedback on performance in both tasks suggesting that affordance perception is rapidly trainable. Further, the aperture task demonstrated that feedback experienced with one hand can transfer to the other. This may have important implications for rehabilitation. © 2016 Randerath and Frey.


Author Keywords
Affordance perception;  Detection theory;  Perception-action;  Training;  Transfer


Document Type: Article
Source: Scopus




White, K.S.a , Pardue, C.a , Ludbrook, P.b , Sodhi, S.b , Esmaeeli, A.b , Cedars, A.b
Cardiac Denial and Psychological Predictors of Cardiac Care Adherence in Adults With Congenital Heart Disease
(2016) Behavior Modification, 40 (1-2), pp. 29-50. 

DOI: 10.1177/0145445515613329


a University of Missouri, St. Louis, United States
b Washington University School of Medicine, St. Louis, MO, United States


Abstract
The current study examined cardiac denial and psychological predictors (i.e., depression, anxiety) of health outcomes including medical nonadherence and physical health in a sample of 80 adults with congenital heart disease (ACHD). Results indicated that denial of impact was elevated in this patient group compared with reference groups, and denial was negatively associated with depression and anxiety at ps <.01. Results indicated that depression, anxiety, and denial predicted unique variance in medical nonadherence, and gender moderated the relationships between these psychological factors and nonadherence. For depression, men and women showed similar relationships between depression and nonadherence at high levels of depression; however, at low levels of depression (i.e., a more normal mood state), men were less adherent compared with women. For anxiety, men and women did not differ in adherence at low levels of anxiety; however, men experiencing high anxiety were less adherent compared with women experiencing high anxiety. Implications of this study are discussed including the role of gender and denial and the impact of denial functioning to reduce negative affect. Depression was the only significant predictor of physical functioning. Results of this study suggest that psychological interventions aimed at depression and anxiety may function differently across gender to improve patient medical adherence and improve physical functioning in ACHD. © 2015, The Author(s) 2015.


Author Keywords
adherence;  congenital heart disease;  denial;  negative affect;  physical functioning


Document Type: Article
Source: Scopus




Mello, M.D., Shriver, A.R., Li, Y., Patel, A., Gyawali, C.P.
Ineffective esophageal motility phenotypes following fundoplication in gastroesophageal reflux disease
(2016) Neurogastroenterology and Motility, 28 (2), pp. 292-298. 

DOI: 10.1111/nmo.12728


Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, United States


Abstract
Background: Ineffective esophageal motility (IEM) is associated with reflux disease, but its natural history is unclear. We evaluated patients undergoing repeat esophageal high resolution manometry (HRM) for symptomatic presentations after antireflux surgery (ARS) to understand the progression of IEM. Methods: Patients with repeat HRM after ARS were included. Ineffective esophageal motility was diagnosed if ≥5 sequences had distal contractile integral (DCI) <450 mmHg cm s. Augmentation of DCI following multiple rapid swallows (MRS) was assessed. The esophagogastric junction (EGJ) was interrogated using the EGJ contractile integral (EGJ-CI). Esophageal motor function was compared between patients with and without IEM. Key Results: Sixty-eight patients (53.9 ± 1.8 years, 66.2% female) had pre- and post-ARS HRM studies 2.1 ± 0.19 years apart. Esophagogastric junction-CI augmented by a mean of 26.3% following ARS. Four IEM phenotypes were identified: 14.7% had persistent IEM, 8.8% resolved IEM after ARS, 19.1% developed new IEM, and 57.4% had no IEM at any point. Patients with IEM had a lower DCI pre- and post-ARS, lower pre-ARS EGJ CI, and lower pre-ARS-integrated relaxation pressure (p ≤ 0.02 for all comparisons); presenting symptoms and other EGJ metrics were similar (p ≥ 0.08 for all comparisons). The IEM phenotypes could be predicted by MRS DCI response patterns (p = 0.008 across groups); patients with persistent IEM had the least DCI augmentation (p = 0.007 compared to no IEM), while those who resolved IEM had DCI augmentation comparable to no IEM (p = 0.08). Conclusions & Inferences: Distinct phenotypes of IEM exist among symptomatic reflux patients following ARS. Provocative testing with MRS may help identify these phenotypes pre-ARS. © 2016 John Wiley & Sons Ltd.


Author Keywords
Gastroesophageal reflux disease;  High resolution manometry;  Ineffective esophageal motility;  Multiple rapid swallows


Document Type: Article
Source: Scopus




Smith, P.J.a , Blumenthal, J.A.a , Trulock, E.P.b , Freedland, K.E.b , Carney, R.M.b , Davis, R.D.c , Hoffman, B.M.a , Palmer, S.M.d
Psychosocial predictors of mortality following lung transplantation
(2016) American Journal of Transplantation, 16 (1), pp. 271-277. 

DOI: 10.1111/ajt.13447


a Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States
b Washington University School of Medicine, St. Louis, MO, United States
c Department of Surgery, Duke University Medical Center, Durham, NC, United States
d Department of Medicine, Duke University Medical Center, Durham, NC, United States


Abstract
Lung transplantation has become an increasingly common treatment for patients with end-stage lung disease. Few studies have examined psychosocial risk factors for mortality in transplant recipients, despite evidence suggesting that elevated levels of negative affect are associated with greater mortality following major cardiac surgery. We therefore examined the relationship between negative affect early after lung transplantation and long-term survival in a sample of 132 lung transplant recipients (28 cystic fibrosis, 64 chronic obstructive pulmonary disease, 26 idiopathic pulmonary fibrosis, 14 other) followed for up to 13.5 years (median 7.4 years) following transplantation. Patients underwent both medical and psychosocial assessments 6 months following transplantation, which included the Beck Depression Inventory-II (BDI-II), Spielberger Anxiety Inventory, and General Health Questionnaire (GHQ). Over the course of follow-up, 80 (61%) participants died. Controlling for demographic factors, native lung disease, disease severity, family income, education level, social support, and frequency of posttransplant rejection, elevated symptoms of depression (BDI-II: HR = 1.31, p = 0.011) and distress (GHQ: HR = 1.28, p = 0.003) were associated with increased mortality. Higher levels of depression and general distress, but not anxiety, measured 6 months following lung transplantation are associated with increased mortality, independent of background characteristics and medical predictors. Lung transplant recipients with elevated levels of depression and psychological distress following transplant exhibit greater long-term mortality rates. Copyright © 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.


Document Type: Article
Source: Scopus




Apte, R.S.
Targeting Tissue Lipids in Age-related Macular Degeneration
(2016) EBioMedicine, . Article in Press. 

DOI: 10.1016/j.ebiom.2016.02.003


Washington University School of Medicine, 660 South Euclid Avenue, Box 8096, St. Louis, MO 63110, United States


Author Keywords
AMD;  Cholesterol;  Eye;  Inflammation;  Lipids;  Macrophage;  Macular degeneration;  Retina


Document Type: Article in Press
Source: Scopus




Jin, X.a , Steinbach, J.H.a b
Potentiation of Neuronal Nicotinic Receptors by 17β-Estradiol: Roles of the Carboxy-Terminal and the Amino-Terminal Extracellular Domains
(2015) PLoS ONE, 10 (12), art. no. e0144631, . 

DOI: 10.1371/journal.pone.0144631


a Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, United States
b Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, Saint Louis, MO, United States


Abstract
The endogenous steroid 17β-estradiol (βEST) potentiates activation of neuronal nicotinic receptors containing α4 subunits. Previous work has shown that the final 4 residues of the α4 subunit are required for potentiation. However, receptors containing the α2 subunit are not potentiated although it has these 4 residues, and only one amino acid difference in the C-Terminal tail (FLAGMI vs. WLAGMI). Previous work had indicated that the tryptophan residue was involved in binding an analog of βEST, but not in potentiation by βEST. To determine the structural basis for the loss of potentiation we analyzed data from chimeric subunits, which indicated that the major factor underlying the difference between α2 and α4 is the tryptophan/phenylalanine difference, while the N-Terminal extracellular domain is a less significant factor. When the tryptophan in α4 was mutated, both phenylalanine and tyrosine conferred lower potentiation while lysine and leucine did not. The reduction reflected a reduced maximal magnitude of potentiation, indicating that the tryptophan is involved in transduction of steroid effects. The regions of the α4 N-Terminal extracellular domain involved in potentiation lie near the agonist-binding pocket, rather than close to the membrane or the C-Terminal tail, and appear to be involved in transduction rather than binding. These observations indicate that the C-Terminal region is involved in both steroid binding (AGMI residues) and transduction (W). The role of the N-Terminus appears to be independent of the C-Terminal tryptophan and likely reflects an influence on conformational changes caused during channel activation by agonist and potentiation by estradiol. © 2015 Jin, Steinbach. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Document Type: Article
Source: Scopus




Swartz, J.R.a , Waller, R.b , Bogdan, R.c , Knodt, A.R.a , Sabhlok, A.a , Hyde, L.W.b , Hariri, A.R.a
A Common Polymorphism in a Williams Syndrome Gene Predicts Amygdala Reactivity and Extraversion in Healthy Adults
(2016) Biological Psychiatry, . Article in Press. 

DOI: 10.1016/j.biopsych.2015.12.007


a Laboratory of Neurogenetics, Department of Psychology and Neuroscience, Duke University, Durham, North Carolina
b Department of Psychology, University of Michigan, Ann Arbor, Michigan
c Department of Psychology, Washington University in St. Louis, St. Louis, Missouri


Abstract
Background: Williams syndrome (WS), a genetic disorder resulting from hemizygous microdeletion of chromosome 7q11.23, has emerged as a model for identifying the genetic architecture of socioemotional behavior. Common polymorphisms in GTF2I, which is found within the WS microdeletion, have been associated with reduced social anxiety in the general population. Identifying neural phenotypes affected by these polymorphisms would help advance our understanding not only of this specific genetic association but also of the broader neurogenetic mechanisms of variability in socioemotional behavior. Methods: Through an ongoing parent protocol, the Duke Neurogenetics Study, we measured threat-related amygdala reactivity to fearful and angry facial expressions using functional magnetic resonance imaging, assessed trait personality using the Revised NEO Personality Inventory, and imputed GTF2I rs13227433 from saliva-derived DNA using custom Illumina arrays. Participants included 808 non-Hispanic Caucasian, African American, and Asian university students. Results: The GTF2I rs13227433 AA genotype, previously associated with lower social anxiety, predicted decreased threat-related amygdala reactivity. An indirect effect of GTF2I genotype on the warmth facet of extraversion was mediated by decreased threat-related amygdala reactivity in women but not men. Conclusions: A common polymorphism in the WS gene GTF2I associated with reduced social anxiety predicts decreased threat-related amygdala reactivity, which mediates an association between genotype and increased warmth in women. These results are consistent with reduced threat-related amygdala reactivity in WS and suggest that common variation in GTF2I contributes to broader variability in socioemotional brain function and behavior, with implications for understanding the neurogenetic bases of WS as well as social anxiety. © 2016 Society of Biological Psychiatry.


Author Keywords
Amygdala;  Emotion;  Extraversion;  FMRI;  GTF2I;  Williams syndrome


Document Type: Article in Press
Source: Scopus




Ng, K.W.a , Connolly, A.M.a b , Zaidman, C.M.a b
Quantitative muscle ultrasound measures rapid declines over time in children with SMA type 1
(2015) Journal of the Neurological Sciences, 358 (1-2), pp. 178-182. 

DOI: 10.1016/j.jns.2015.08.1532


a Washington University, School of Medicine, Department of Neurology, St. Louis, MO, United States
b Washington University, School of Medicine, Department of Pediatrics, St. Louis, MO, United States


Abstract
Muscles are small in spinal muscular atrophy (SMA). It is not known if muscle size changes over time in SMA type 1. We quantified changes over time in muscle size and echointensity during two repeated ultrasound examinations of unilateral proximal (biceps brachii/brachialis and quadriceps) and distal (anterior forearm flexors and tibialis anterior) muscles in three children with SMA type 1. We compared muscle thickness (MT) to body weight-dependent normal reference values. Children were 1, 6, and 11 months old at baseline and had 2, 2 and 4 months between ultrasound examinations, respectively. At baseline, MT was normal for weight in all muscles except an atrophic quadriceps in the oldest child. MT decreased and echointensity increased (worsened) over time. At follow up, MT was below normal for weight in the quadriceps in all three children, in the biceps/brachioradialis in two, and in the anterior forearm in one. Tibialis anterior MT remained normal for weight in all three children. Muscle echointensity increased over time in all muscles and, on average, more than doubled in two children. In children with SMA type 1, muscle atrophies and becomes hyperechoic over time. Quantitative muscle ultrasound measures disease progression in SMA type 1 that warrants additional study in more children. © 2015 Published by Elsevier B.V.


Author Keywords
Backscatter;  Children;  Muscle;  Spinal muscular atrophy;  Ultrasound


Document Type: Article
Source: Scopus




Elfenbein, H.A.
In-Group Advantage and Other-Group Bias in Facial Emotion Recognition
(2015) Understanding Facial Expressions in Communication: Cross-Cultural and Multidisciplinary Perspectives, pp. 57-71. 

DOI: 10.1007/978-81-322-1934-7_4


Washington University in St. Louis, St. Louis, United States


Abstract
This chapter summarizes the body of work about cultural differences in emotion recognition based on the match versus mismatch of the cultural group expressing the emotion and the cultural group perceiving the emotion. Two major perspectives have arisen to explain the well-replicated empirical finding that there tends to be better recognition of facial expressions where there is a match. The first is the notion of in-group advantage, which is an information-based explanation, arguing that individuals are more accurate judging emotional expressions from their own cultural group versus foreign groups due to better information about culturally specific elements of emotional expression. The finding of systematic in-group advantage has led to the development of a recent dialect theory of emotion, which uses a linguistic metaphor to argue emotion is a universal language with subtly different dialects. Just as it is more challenging to understand someone speaking a different dialect in verbal language, it can be more challenging to recognize emotions that are expressed in a different dialect. This dialect theory has been the subject of controversy due to its implications for dominant theories about cross-cultural differences in emotion. A second perspective is the notion of out-group bias, which is a motivation-based explanation. Individuals may use decoding rules to understand out-group emotional expressions differently, or they may be less motivated to recognize the emotions of other individuals who are members of foreign cultures, even when they are merely lead to believe falsely that expressions originate elsewhere. Both of these theoretical mechanisms can act singly or simultaneously. © Springer India 2015.


Author Keywords
Decoding rules;  Dialect;  Display rules;  In-group advantage;  Other-group bias


Document Type: Book Chapter
Source: Scopus




Poreddi, V.a , Carpenter, B.D.b , Gandhi, S.c , Chandra, R.a , BadaMath, S.d
Knowledge and attitudes of undergraduate nursing students toward dementia: An Indian perspective
(2015) Investigacion y Educacion en Enfermeria, 33 (3), pp. 519-528. 

DOI: 10.17533/udea.iee.v33n3a16


a College of Nursing, Department of Nursing, National Institute of Mental health and Neurosciences, India
b Washington University, St. Louis, United States
c Department of Nursing, National Institute of Mental Health and Neurosciences, India
d Department of Psychiatry, National Institute of Mental health and Neurosciences, India


Abstract
Objective. This work evaluated nursing students' knowledge and attitudes toward individuals with Alzheimer's disease and dementia. Methodology. This was a transversal, descriptive study carried out with a randomly selected group of nursing students (N = 122) from Bangalore, India, in 2013. The study used the Alzheimer's Disease Knowledge scale (30 questions with true-false options) and the Attitude toward Alzheimer's Disease and Related Dementias scale (20 questions scored with seven Likert-type options; the higher the score, the better the attitude). Results. The findings revealed that 56% of the questions were answered correctly and the average attitude score was 95 ± 1.5. A negative correlation was observed between age and knowledge of dementia (r = -0.323; p < 0.01). Conclusion. The participants have inadequate knowledge of dementia. However, they have positive attitudes towards patients with dementia, giving way to improving their knowledge related to this disease. Thereby, there is urgent need to enhance the undergraduate study plan with respect to the content of this theme and strengthen the attitudes of comprehensive care to individuals with dementia.


Author Keywords
Alzheimer disease;  Attitude;  Cross-sectional studies;  Dementia;  India;  Students, nursing

 


Document Type: Article
Source: Scopus

 

February 12, 2016

Lee, Y.-S.a , Min, N.E.a , Wingfield, A.b , Grossman, M.a , Peelle, J.E.c
Acoustic richness modulates the neural networks supporting intelligible speech processing
(2016) Hearing Research, 333, pp. 108-117. 

DOI: 10.1016/j.heares.2015.12.008
 

a Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, PA, United States
b Volen National Center for Complex Systems, Brandeis University, Waltham, MA, United States
c Department of Otolaryngology, Washington University in St. Louis, St. Louis, MO, United States
 

Abstract
The information contained in a sensory signal plays a critical role in determining what neural processes are engaged. Here we used interleaved silent steady-state (ISSS) functional magnetic resonance imaging (fMRI) to explore how human listeners cope with different degrees of acoustic richness during auditory sentence comprehension. Twenty-six healthy young adults underwent scanning while hearing sentences that varied in acoustic richness (high vs. low spectral detail) and syntactic complexity (subject-relative vs. object-relative center-embedded clause structures). We manipulated acoustic richness by presenting the stimuli as unprocessed full-spectrum speech, or noise-vocoded with 24 channels. Importantly, although the vocoded sentences were spectrally impoverished, all sentences were highly intelligible. These manipulations allowed us to test how intelligible speech processing was affected by orthogonal linguistic and acoustic demands. Acoustically rich speech showed stronger activation than acoustically less-detailed speech in a bilateral temporoparietal network with more pronounced activity in the right hemisphere. By contrast, listening to sentences with greater syntactic complexity resulted in increased activation of a left-lateralized network including left posterior lateral temporal cortex, left inferior frontal gyrus, and left dorsolateral prefrontal cortex. Significant interactions between acoustic richness and syntactic complexity occurred in left supramarginal gyrus, right superior temporal gyrus, and right inferior frontal gyrus, indicating that the regions recruited for syntactic challenge differed as a function of acoustic properties of the speech. Our findings suggest that the neural systems involved in speech perception are finely tuned to the type of information available, and that reducing the richness of the acoustic signal dramatically alters the brain's response to spoken language, even when intelligibility is high. © 2015 Elsevier B.V.
 

Author Keywords
Acoustic;  Executive function;  FMRI;  Hearing;  Language;  Listening effort;  Speech;  Vocoding
 


Document Type: Article
Source: Scopus


 

Zimmerman, C.a , Atherton, P.J.b , Pachman, D.b , Seisler, D.b , Wagner-Johnston, N.c , Dakhil, S.d , Lafky, J.M.a , Qin, R.a b , Grothey, A.a , Loprinzi, C.L.a
MC11C4: a pilot randomized, placebo-controlled, double-blind study of venlafaxine to prevent oxaliplatin-induced neuropathy
(2016) Supportive Care in Cancer, 24 (3), pp. 1071-1078. 

DOI: 10.1007/s00520-015-2876-5
 

a Mayo Clinic, 200 1st St SW, Rochester, MN, United States
b Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, United States
c Washington University School of Medicine, St. Louis, MO, United States
d Cancer Center of Kansas, Wichita, KS, United States
 

Abstract
Purpose: Previous pilot data suggested that venlafaxine could prevent acute and chronic oxaliplatin-related neuropathy. The purpose of this randomized, placebo-controlled, double-blinded pilot study was to obtain additional data to support conducting a phase III trial to test the use of venlafaxine to prevent oxaliplatin neurotoxicity. Methods: Fifty patients, scheduled to undergo oxaliplatin-based therapy (FOLFOX) for stages II–III (67 %) or stage IV (33 %) colon cancer, were randomized to receive venlafaxine extended release (37.5 mg) or placebo, twice daily, through their last dose of oxaliplatin and then titrated off. Neurotoxicity was evaluated via several patient- and physician-reported measures, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20) instrument. Results: Baseline patient characteristics were equivalent for the two arms, with a median age of 60 years. There was a trend toward benefit for the venlafaxine arm, when evaluated by the oxaliplatin-specific neuropathy scale and by acute neuropathy measures of throat discomfort and discomfort swallowing cold liquids, the latter only for the first two oxaliplatin doses. These trends were outweighed by a lack of any such trends in all other measurements including the following: (1) the CIPN20 sensory subscale (P = 0.55, primary endpoint), physician-completed NCI CTCAE assessment, or cumulative administered oxaliplatin doses (median 716 vs 631 mg for placebo and venlafaxine, respectively, P = 0.34). Conclusions: The present study neither supports the use of venlafaxine for preventing oxaliplatin-induced neuropathy in clinical practice nor the initiation of a phase III trial to investigate venlafaxine in this setting. © 2015, Springer-Verlag Berlin Heidelberg.
 

Author Keywords
Chemotherapy-induced neuropathy prevention;  Venlafaxine
 


Document Type: Article
Source: Scopus
 



 

Godzik, J.a , Dardas, A.b , Kelly, M.P.c , Holekamp, T.F.b , Lenke, L.G.c , Smyth, M.D.b d , Park, T.S.b d , Leonard, J.R.b d , Limbrick, D.D.b d
Comparison of spinal deformity in children with Chiari I malformation with and without syringomyelia: matched cohort study
(2016) European Spine Journal, 25 (2), pp. 619-626. 

DOI: 10.1007/s00586-015-4011-1
 

a Department of Neurosurgery, Barrow Neurological Institute, 350 W. Thomas Road, Phoenix, AZ, United States
b Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
c Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pediatric Neurosurgery, St. Louis Children’s Hospital, St. Louis, MO, United States
 

Abstract
Purpose: To describe curve patterns in patients with Chiari malformation I (CIM) without syringomyelia, and compare to patients with Chiari malformation with syringomyelia (CIM + SM). Methods: Review of medical records from 2000 to 2013 at a single institution was performed to identify CIM patients with scoliosis. Patients with CIM were matched (1:1) by age and gender to CIM + SM. Radiographic curve patterns, MRI-based craniovertebral junction parameters, and associated neurological signs were compared between the two cohorts. Results: Eighteen patients with CIM-associated scoliosis in the absence of syringomyelia were identified; 14 (78 %) were female, with mean age of 11.5 ± 4.5 years. Mean tonsillar descent was 9.9 ± 4.1 mm in the CIM group and 9.1 ± 3.0 mm in the CIM + SM group (p = 0.57). Average syrinx diameter in the CIM + SM group was 9.0 ± 2.7 mm. CIM patients demonstrated less severe scoliotic curves (32.1° vs. 46.1°, p = 0.04), despite comparable thoracic kyphosis (43.7° vs. 49.6°, p = 0.85). Two (11 %) patients with CIM demonstrated thoracic apex left deformities compared to 9/18 (50 %) in the CIM + SM cohort (p = 0.01). Neurological abnormalities were only observed in the group with syringomyelia (6/18, or 33 %; p = 0.007). Conclusion: In the largest series specifically evaluating CIM and scoliosis, we found that these patients appear to present with fewer atypical curve features, with less severe scoliotic curves, fewer apex left curves, and fewer related neurological abnormalities than CIM + SM. Notably, equivalent thoracic kyphosis was observed in both groups. Future studies are needed to better understand pathogenesis of spinal deformity in CIM with and without SM. © 2015, Springer-Verlag Berlin Heidelberg.
 

Author Keywords
Chiari malformation;  Kyphosis;  Scoliosis;  Spinal deformity;  Syringomyelia
 


Document Type: Article
Source: Scopus
 



 

Sylvester, C.M.a , Hudziak, J.J.b , Gaffrey, M.S.a , Barch, D.M.a c d , Luby, J.L.a
Stimulus-Driven Attention, Threat Bias, and Sad Bias in Youth with a History of an Anxiety Disorder or Depression
(2016) Journal of Abnormal Child Psychology, 44 (2), pp. 219-231. 

DOI: 10.1007/s10802-015-9988-8
 

a Department of Psychiatry, Washington University School of Medicine, 4444 Forest Park Avenue, Campus Box 8511, St. Louis, MO, United States
b Department of Psychiatry, University of Vermont College of Medicine, 1 South Prospect, UHC St. Joseph’s, Burlington, VT, United States
c Department of Psychology, Washington University School of Medicine, One Brookings Drive, Campus Box 1125, St. Louis, MO, United States
d Department of Radiology, Washington University School of Medicine, One Brookings Drive, Campus Box 1125, St. Louis, MO, United States
 

Abstract
Attention biases towards threatening and sad stimuli are associated with pediatric anxiety and depression, respectively. The basic cognitive mechanisms associated with attention biases in youth, however, remain unclear. Here, we tested the hypothesis that threat bias (selective attention for threatening versus neutral stimuli) but not sad bias relies on stimulus-driven attention. We collected measures of stimulus-driven attention, threat bias, sad bias, and current clinical symptoms in youth with a history of an anxiety disorder and/or depression (ANX/DEP; n = 40) as well as healthy controls (HC; n = 33). Stimulus-driven attention was measured with a non-emotional spatial orienting task, while threat bias and sad bias were measured at a short time interval (150 ms) with a spatial orienting task using emotional faces and at a longer time interval (500 ms) using a dot-probe task. In ANX/DEP but not HC, early attention bias towards threat was negatively correlated with later attention bias to threat, suggesting that early threat vigilance was associated with later threat avoidance. Across all subjects, stimulus-driven orienting was not correlated with early threat bias but was negatively correlated with later threat bias, indicating that rapid stimulus-driven orienting is linked to later threat avoidance. No parallel relationships were detected for sad bias. Current symptoms of depression but not anxiety were related to decreased stimulus-driven attention. Together, these results are consistent with the hypothesis that threat bias but not sad bias relies on stimulus-driven attention. These results inform the design of attention bias modification programs that aim to reverse threat biases and reduce symptoms associated with pediatric anxiety and depression. © 2015, Springer Science+Business Media New York.
 

Author Keywords
Adolescent;  Anxiety;  Attention bias;  Depression;  Sad bias;  Stimulus-driven attention;  Threat bias
 


Document Type: Article
Source: Scopus
 



 

Avidan, M.S., Evers, A.S.
The Fallacy of Persistent Postoperative Cognitive Decline
(2016) Anesthesiology, 124 (2), pp. 255-258. 

DOI: 10.1097/ALN.0000000000000958
 

Department of Anesthesiology, Washington University, School of Medicine, St. Louis, MO, United States
 
 
 


Document Type: Review
Source: Scopus
 



 

Palmer, R.H.C.a b e , Bidwell, L.C.c , Heath, A.C.d , Brick, L.A.a , Madden, P.A.F.d , Knopik, V.S.a b
Effects of Maternal Smoking during Pregnancy on Offspring Externalizing Problems: Contextual Effects in a Sample of Female Twins
(2016) Behavior Genetics, pp. 1-13. Article in Press. 

DOI: 10.1007/s10519-016-9779-1
 

a Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, United States
b Department of Psychiatry & Human Behavior, Alpert Medical School of Brown University, Providence, RI, United States
c Institute for Cognitive Sciences, University of Colorado at Boulder, Boulder, CO, United States
d Midwestern Alcohol Research Center, Washington University, St. Louis, MO, United States
e Bradley Hasbro Children’s Research Center Coro West, 1 Hoppin St, Suite 204, Providence, RI, United States
 

Abstract
Studies of maternal smoking during pregnancy (MSDP) suggest increased risk for cognitive impairment and psychiatric outcomes. However, it is uncertain whether these associations are the direct result of MSDP or related to confounding familial variables associated with MSDP. The current study employed propensity score analysis to examine the effects of MSDP on offspring EXT using data from a large sample of 979 unrelated mothers. Logistic regression models were used to determine the propensity that the offspring of these mothers were likely to be exposed to MSDP [i.e., smoked during only the first trimester (MSDP-EARLY[E]) or smoked throughout their pregnancy (MSDP-THROUGHOUT[T])] given known familial confounders. Analyses focused on the effect of MSDP-E/T on the EXT behavior in offspring of these mothers (N = 1616) were conducted across the distribution of liability for MSDP-E/T and at different levels of risk for MSDP-E/T. MSDP-E/T was associated with offspring EXT problems, but the effects were partly confounded by the familial liability for MSDP. Further, the observed effects were not consistent across all levels of the MSDP risk distribution. These findings suggest a direct association between MSDP and offspring EXT behaviors, and that varied associations observed across studies may be the result of differences in the level of familial confounders that also have an effect on offspring EXT. © 2016 Springer Science+Business Media New York
 

Author Keywords
ADHD;  Alcohol dependence;  Conduct disorder;  Smoking during pregnancy;  Tobacco dependence
 


Document Type: Article in Press
Source: Scopus
 



 

Ceccarelli, M.a b x , Barthel, F.P.c d , Malta, T.M.e f , Sabedot, T.S.e f , Salama, S.R.g , Murray, B.A.h , Morozova, O.g , Newton, Y.g , Radenbaugh, A.g , Pagnotta, S.M.b i , Anjum, S.a , Wang, J.j , Manyam, G.c , Zoppoli, P.j , Ling, S.c , Rao, A.A.g , Grifford, M.g , Cherniack, A.D.h , Zhang, H.h , Poisson, L.k , Carlotti, C.G., Jr.e f , Tirapelli, D.P.D.C.e f , Rao, A.c , Mikkelsen, T.k , Lau, C.C.l m , Yung, W.K.A.c , Rabadan, R.j , Huse, J.n , Brat, D.J.o , Lehman, N.L.p , Barnholtz-Sloan, J.S.q , Zheng, S.c , Hess, K.c , Rao, G.c , Meyerson, M.h r , Beroukhim, R.h r s , Cooper, L.o , Akbani, R.c , Wrensch, M.t , Haussler, D.g , Aldape, K.D.u , Laird, P.W.v , Gutmann, D.H.w , Noushmehr, H.e f , Iavarone, A.j , Verhaak, R.G.W.c
Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma
(2016) Cell, 164 (3), pp. 550-563. 

DOI: 10.1016/j.cell.2015.12.028
 

a Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha P.O. box 5825, Qatar
b Department of Science and Technology, University of Sannio, Benevento, Italy
c Department of Genomic Medicine, Department of Bioinformatics and Computational Biology, Department of Biostatistics, Department of Neuro-Oncology, Department of Neurosurgery, Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
d Oncology Graduate School Amsterdam, Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, Netherlands
e Department of Genetics (CISBi/NAP), Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Monte Alegre, Ribeirão Preto-SP, Brazil
f Center for Integrative Systems Biology (CISBi NAP/USP), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
g UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, United States
h Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology, Harvard University, Cambridge, MA, United States
i BIOGEM Istituto di Ricerche Genetiche G. Salvatore, Campo Reale, Ariano Irpino, Italy
j Department of Neurology, Department of Pathology, Institute for Cancer Genetics, Department of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY, United States
k Henry Ford Hospital, Detroit, MI, United States
l Texas Children's Hospital, Houston, TX, United States
m Baylor College of Medicine, Houston, TX, United States
n Memorial Sloan Kettering Cancer Center, New York, NY, United States
o Winship Cancer Institute, Emory University, Atlanta, GA, United States
p Department of Pathology, Ohio State University, Columbus, OH, United States
q Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States
r Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
s Department of Medicine, Harvard Medical School, Boston, MA, United States
t Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States
u Princess Margaret Cancer Centre, Toronto, ON, Canada
v Van Andel Research Institute, Grand Rapids, MI, United States
w School of Medicine, Washington University, St. Louis, MO, United States
 

Abstract
Summary Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. © 2016 Elsevier Inc.
 
 


Document Type: Article
Source: Scopus
 



 

Laine, V.N.a , Gossmann, T.I.b , Schachtschneider, K.M.c d , Garroway, C.J.e , Madsen, O.c , Verhoeven, K.J.F.f , De Jager, V.a , Megens, H.-J.c , Warren, W.C.g , Minx, P.g , Crooijmans, R.P.M.A.c , Corcoran, P.b , Adriaensen, F.h , Belda, E.i , Bushuev, A.j , Cichon, M.k , Charmantier, A.l , Dingemanse, N.m , Doligez, B.n , Eeva, T.o , Erikstad, K.E.p , Fedorov, S.q , Hau, M.m , Hille, S.r , Hinde, C.s , Kempenaers, B.m , Kerimov, A.j , Krist, M.t , Mand, R.u , Matthysen, E.h , Nager, R.v , Norte, C.w , Orell, M.x , Richner, H.y , Slagsvold, T.z , Tilgar, V.u , Tinbergen, J.aa , Torok, J.ab , Tschirren, B.ac , Yuta, T.ad , Sheldon, B.C.e , Slate, J.b , Zeng, K.b , Van Oers, K.a , Visser, M.E.a c , Groenen, M.A.M.c
Evolutionary signals of selection on cognition from the great tit genome and methylome
(2016) Nature Communications, 7, art. no. 10474, . 

DOI: 10.1038/ncomms10474
 

a Department of Animal Ecology, Netherlands Institute of Ecology (NIOO-KNAW), P.O. Box 50, Wageningen, Netherlands
b Department of Animal and Plant Sciences, University of Sheffield, Sheffield, United Kingdom
c Animal Breeding and Genomics Centre, Wageningen University, P.O. Box 338, Wageningen, Netherlands
d Department of Animal Sciences, University of Illinois, Urbana, IL, United States
e Edward Grey Institute, Department of Zoology, University of Oxford, Oxford, United Kingdom
f Department of Terrestrial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), P.O. Box 50, Wageningen, Netherlands
g Genome Institute, Washington University School of Medicine, St Louis, MO, United States
h Evolutionary Ecology Group, Department of Biology, University of Antwerp, Antwerp, Belgium
i Departamento de Ciencia Animal, IGIC, Universidad Politécnica de Valencia, C/Paranimf no1, Gandía, Valencia, Spain
j Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation
k Inst. of Environmental Sciences, Jagiellonian University, Gronostajowa 7, Kraków, Poland
l CEFE-CNRS, UMR 5175, 1919, route de Mende, Montpellier Cedex 5, France
m Max Planck Institute for Ornithology, Department of Behavioural Ecology and Evolutionary Genetics, Eberhard-Gwinner-Straße, House 5, Seewiesen (Starnberg), Germany
n UMR CNRS 5558 LBBE, Biométrie et Biologie Évolutive, UCB Lyon 1 - Bât. Grégor Mendel, 43 bd du 11 novembre 1918, Villeurbanne Cedex, France
o Section of Ecology, Department of Biology, University of Turku, Turku, Finland
p Norwegian Institute for Nature Research, FRAM-High North Research Centre for Climate and the Environment, Tromsø, Norway
q Department of Vertebrate Zoology, Moscow State University, Moscow, Russian Federation
r Institute of Wildlife Biology and Game Management, University of Natural Resources and Life Science, Vienna, Austria
s Behavioural Ecology Group, Department of Animal Sciences, Wageningen University, Wageningen, Netherlands
t Department of Zoology, Laboratory of Ornithology, Faculty of Science, Palacký University, Olomouc, Czech Republic
u Department of Zoology, Institute of Ecology and Earth Sciences, University of Tartu, Vanemuise 46, Tartu, Estonia
v Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, United Kingdom
w Department of Life Sciences, Institute of Marine Research IMAR/CMA, University of Coimbra, Coimbra, Portugal
x Department of Biology, University of Oulu, P.O. Box 3000, Oulu, Finland
y Evolutionary Ecology Lab., Institute of Ecology and Evolution, University of Bern, Bern, Switzerland
z Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences, University of Oslo, P.O. Box 1066, Blindern, Oslo, Norway
aa Centre for Ecological and Evolutionary Studies (CEES), Univ. of Groningen, PO Box 11103, Groningen, Netherlands
ab Behavioural Ecology Group, Department of Systematic Zoology and Ecology, Eötvös Loránd University, Budapest, Hungary
ac Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland
ad Graduate School of Environmental Science, Hokkaido University, Hokkaido 060-0810, Sapporo, Japan
 

Abstract
For over 50 years, the great tit (Parus major) has been a model species for research in evolutionary, ecological and behavioural research; in particular, learning and cognition have been intensively studied. Here, to provide further insight into the molecular mechanisms behind these important traits, we de novo assemble a great tit reference genome and whole-genome re-sequence another 29 individuals from across Europe. We show an overrepresentation of genes related to neuronal functions, learning and cognition in regions under positive selection, as well as increased CpG methylation in these regions. In addition, great tit neuronal non-CpG methylation patterns are very similar to those observed in mammals, suggesting a universal role in neuronal epigenetic regulation which can affect learning-, memory- and experience-induced plasticity. The high-quality great tit genome assembly will play an instrumental role in furthering the integration of ecological, evolutionary, behavioural and genomic approaches in this model species. © 2016, Nature Publishing Group. All rights reserved.
 
 


Document Type: Article
Source: Scopus
 



 

Kharasch, E.D., Brunt, L.M.
Perioperative Opioids and Public Health
(2016) Anesthesiology, . Article in Press. 

DOI: 10.1097/ALN.0000000000001012
 

From the Division of Clinical and Translational Research, Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri (E.D.K.); Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, Missouri (E.D.K.); Department of Surgery, Section of Minimally Invasive Surgery, Washington University in St. Louis, St. Louis, Missouri (L.M.B.); and The Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University in St. Louis, St. Louis, Missouri (E.D.K.).
 
 
 


Document Type: Article in Press
Source: Scopus
 



 

Reynolds, M.R.a , Singh, I.a , Azad, T.D.a , Holmes, B.B.b , Verghese, P.B.b , Dietrich, H.H.a , Diamond, M.c , Bu, G.d , Han, B.H.e , Zipfel, G.J.a b
Heparan sulfate proteoglycans mediate Aβ-induced oxidative stress and hypercontractility in cultured vascular smooth muscle cells
(2016) Molecular Neurodegeneration, 11 (1), art. no. 9, . 

DOI: 10.1186/s13024-016-0073-8
 

a Department of Neurological Surgery, Washington University School of Medicine, Hope Center Program on Protein Aggregation and Neurodegeneration, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Campus Box 8057, 660 South Euclid Avenue, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, Hope Center Program on Protein Aggregation and Neurodegeneration, Charles F. and Joanne Knight Alzheimer's Disease Research Center, St. Louis, MO, United States
c Center for Alzheimer's and Neurodegenerative Diseases, UT Southwestern, Dallas, TX, United States
d Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
e Department of Pharmacology, AT Still University Health Sciences, Kirksville, MO, United States
 

Abstract
Background: Substantial evidence suggests that amyloid-β (Aβ) species induce oxidative stress and cerebrovascular (CV) dysfunction in Alzheimer's disease (AD), potentially contributing to the progressive dementia of this disease. The upstream molecular pathways governing this process, however, are poorly understood. In this report, we examine the role of heparan sulfate proteoglycans (HSPG) in Aβ-induced vascular smooth muscle cell (VSMC) dysfunction in vitro. Results: Our results demonstrate that pharmacological depletion of HSPG (by enzymatic degradation with active, but not heat-inactivated, heparinase) in primary human cerebral and transformed rat VSMC mitigates Aβ1-40- and Aβ1-42-induced oxidative stress. This inhibitory effect is specific for HSPG depletion and does not occur with pharmacological depletion of other glycosaminoglycan (GAG) family members. We also found that Aβ1-40 (but not Aβ1-42) causes a hypercontractile phenotype in transformed rat cerebral VSMC that likely results from a HSPG-mediated augmentation in intracellular Ca2+ activity, as both Aβ1-40-induced VSMC hypercontractility and increased Ca2+ influx are inhibited by pharmacological HSPG depletion. Moreover, chelation of extracellular Ca2+ with ethylene glycol tetraacetic acid (EGTA) does not prevent the production of Aβ1-40- or Aβ1-42-mediated reactive oxygen species (ROS), suggesting that Aβ-induced ROS and VSMC hypercontractility occur through different molecular pathways. Conclusions: Taken together, our data indicate that HSPG are critical mediators of Aβ-induced oxidative stress and Aβ1-40-induced VSMC dysfunction. © 2016 Reynolds et al.
 

Author Keywords
Alzheimer's disease;  Cerebrovascular dysfunction;  Heparan sulfate proteoglycans;  Heparin;  Heparinase;  Oxidative stress;  Reactive oxygen species;  Vascular smooth muscle cells
 


Document Type: Article
Source: Scopus
 



 

Leuthardt, E.C., Allen, M., Kamran, M., Hawasli, A.H., Snyder, A.Z., Hacker, C.D., Mitchell, T.J., Shimony, J.S.
Resting-State Blood Oxygen Level-Dependent Functional MRI: A Paradigm Shift in Preoperative Brain Mapping
(2016) Stereotactic and Functional Neurosurgery, pp. 427-439. Article in Press. 

DOI: 10.1159/000442424
 

Washington University School of Medicine, Saint Louis, Mo., USA
 

Abstract
Currently, functional magnetic resonance imaging (fMRI) facilitates a preoperative awareness of an association of an eloquent region with a tumor. This information gives the neurosurgeon helpful information that can aid in creating a surgical strategy. Typically, task-based fMRI has been employed to preoperatively localize speech and motor function. Task-based fMRI depends on the patient's ability to comply with the task paradigm, which often is impaired in the setting of a brain tumor. This problem is overcome by using resting-state fMRI (rs-fMRI) to localize function. rs-fMRI measures spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, representing the brain's functional organization. In a neurosurgical context, it allows noninvasive simultaneous assessment of multiple large-scale distributed networks. Compared with task-related fMRI, rs-fMRI provides more comprehensive information on the functional architecture of the brain and is applicable in settings where task-related fMRI may provide inadequate information or could not be performed. Taken together, rs-fMRI substantially expands the preoperative mapping capability in efficiency, effectiveness, and scope. In this article, a brief introduction into rs-fMRI processing methods is followed by a detailed discussion on the role rs-fMRI plays in presurgical planning. © 2016 S. Karger AG, Basel
 

Author Keywords
Functional MRI;  Multilayer perceptron#;  Resting state networks;  Resting-state functional MRI
 


Document Type: Article in Press
Source: Scopus
 



 

Wilson, U.S.a c , Kaf, W.A.a , Danesh, A.A.b , Lichtenhan, J.T.c
Assessment of low-frequency hearing with narrow-band chirp-evoked 40-Hz sinusoidal auditory steady-state response
(2016) International Journal of Audiology, pp. 1-9. Article in Press. 

DOI: 10.3109/14992027.2015.1122238
 

a Communication Sciences and Disorders, Missouri State University, Springfield, Missouri, USA
b Communication Sciences and Disorders, Florida Atlantic University, Boca Raton, Florida, USA
c Department of Otolaryngology, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
 

Abstract
Objective To determine the clinical utility of narrow-band chirp-evoked 40-Hz sinusoidal auditory steady state responses (s-ASSR) in the assessment of low-frequency hearing in noisy participants. Design Tone bursts and narrow-band chirps were used to respectively evoke auditory brainstem responses (tb-ABR) and 40-Hz s-ASSR thresholds with the Kalman-weighted filtering technique and were compared to behavioral thresholds at 500, 2000, and 4000 Hz. A repeated measure ANOVA and post-hoc t-tests, and simple regression analyses were performed for each of the three stimulus frequencies. Study sample Thirty young adults aged 18–25 with normal hearing participated in this study. Results When 4000 equivalent response averages were used, the range of mean s-ASSR thresholds from 500, 2000, and 4000 Hz were 17–22 dB lower (better) than when 2000 averages were used. The range of mean tb-ABR thresholds were lower by 11–15 dB for 2000 and 4000 Hz when twice as many equivalent response averages were used, while mean tb-ABR thresholds for 500 Hz were indistinguishable regardless of additional response averaging. Conclusion Narrow-band chirp-evoked 40-Hz s-ASSR requires a ∼15 dB smaller correction factor than tb-ABR for estimating low-frequency auditory threshold in noisy participants when adequate response averaging is used. © 2016 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society
 
 


Document Type: Article in Press
Source: Scopus
 



 

Siuda, E.R., Al-Hasani, R., McCall, J.G., Bhatti, D.L., Bruchas, M.R.
Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States
(2016) Neuropsychopharmacology, . Article in Press. 

DOI: 10.1038/npp.2015.371
 

Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St Louis, Missouri, USA
 

Abstract
Anxiety disorders are debilitating psychiatric illnesses with detrimental effects on human health. These heightened states of arousal are often in the absence of obvious threatening cues and are difficult to treat owing to a lack of understanding of the neural circuitry and cellular machinery mediating these conditions. Activation of noradrenergic circuitry in the basolateral amygdala is thought to have a role in stress, fear, and anxiety, and the specific cell and receptor types responsible is an active area of investigation. Here we take advantage of two novel cellular approaches to dissect the contributions of G-protein signaling in acute and social anxiety-like states. We used a chemogenetic approach utilizing the Gαs DREADD (rM3Ds) receptor and show that selective activation of generic Gαs signaling is sufficient to induce acute and social anxiety-like behavioral states in mice. Second, we use a recently characterized chimeric receptor composed of rhodopsin and the β2-adrenergic receptor (Opto-β2AR) with in vivo optogenetic techniques to selectively activate Gαs β-adrenergic signaling exclusively within excitatory neurons of the basolateral amygdala. We found that optogenetic induction of β-adrenergic signaling in the basolateral amygdala is sufficient to induce acute and social anxiety-like behavior. These findings support the conclusion that activation of Gαs signaling in the basolateral amygdala has a role in anxiety. These data also suggest that acute and social anxiety-like states may be mediated through signaling pathways identical to β-adrenergic receptors, thus providing support that inhibition of this system may be an effective anxiolytic therapy.Neuropsychopharmacology advance online publication, 27 January 2016; doi:10.1038/npp.2015.371. © 2016 American College of Neuropsychopharmacology
 
 


Document Type: Article in Press
Source: Scopus
 



 

Jacobs, J.V.a b , Earhart, G.M.c d e , McNeely, M.E.c d
Can postural instability tests improve the prediction of future falls in people with Parkinson’s disease beyond knowing existing fall history?
(2016) Journal of Neurology, 263 (1), pp. 133-139. 

DOI: 10.1007/s00415-015-7950-x
 

a Liberty Mutual Research Institute for Safety, 71 Frankland Rd, Hopkinton, MA, United States
b Department of Rehabilitation and Movement Science, University of Vermont, 305 Rowell Building, 106 Carrigan Drive, Burlington, VT, United States
c Program in Physical Therapy, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
d Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
e Department of Anatomy and Neurobiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
 

Abstract
This study sought to determine whether the backward-stepping Push and Release (P&R) Test and the Pull Test, or comprehensive batteries of postural instability (the Mini-BESTest and Brief-BESTest), significantly improve the prediction of future falls beyond knowing a person’s baseline fall history. Complete data were available for 43 of 80 participants with PD. At baseline, participants completed the BESTest (which was scored for all versions and includes the P&R Test), the Unified PD Rating Scale (UPDRS) motor section (which includes the Pull Test), and the participants’ reported falls experienced in the previous 6 months. Participants were classified as recurrent fallers if they reported more than one fall in the 12 months subsequent to baseline. Stepwise logistic regressions determined whether the P&R Test, Pull Test, Brief-BESTest, Mini-BESTest, or UPDRS motor score improved predictions of recurrent fallers independent of baseline fall-group status. Independently, all assessments significantly predicted future recurrent fallers, but only the Mini-BESTest and Brief-BESTest significantly improved predictions of future recurrent fallers independent of baseline fall-group status. The results suggest that, although single tests of reactive postural control do not offer significant predictive benefit, predictions of future recurrent fallers with PD do benefit from a balance examination in addition to knowing whether an individual has a recent history of falls. © 2015, Springer-Verlag Berlin Heidelberg.
 

Author Keywords
BESTest;  Falls;  Parkinson’s disease;  Pull Test;  Push and Release Test
 


Document Type: Article
Source: Scopus
 



 

Saper, C.B.a , Loewy, A.D.b
Commentary on: Efferent connections of the parabrachial nucleus in the rat. C.B. Saper and A.D. Loewy, Brain Research 197:291-317, 1980
(2016) Brain Research, . Article in Press. 

DOI: 10.1016/j.brainres.2016.01.009
 

a Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA
b Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA
 

Abstract
By the late 1970's, the pathways had been identified from neurons in the nucleus of the solitary tract that control visceral sensory inflow and from the paraventricular nucleus and lateral hypothalamus that directly innervate the autonomic preganglionic neurons, thereby controlling autonomic outflow. However, the connections between the two were not yet clear. This paper identified the parabrachial nucleus as a key intermediary, receiving the bulk of outflow from the nucleus of the solitary tract and distributing it to a set of brainstem and forebrain sites that constituted a central autonomic control network. This work also identified the insular cortex as a key visceral sensory cortical area. This article is part of a Special Issue entitled SI:50th Anniversary Issue. © 2016 Elsevier B.V.
 

Author Keywords
Autonomic;  Insular;  Parabrachial
 


Document Type: Article in Press
Source: Scopus
 



 

Bruchas, M.R.a , Roth, B.L.b
New Technologies for Elucidating Opioid Receptor Function
(2016) Trends in Pharmacological Sciences, . Article in Press. 

DOI: 10.1016/j.tips.2016.01.001
 

a Departments of Anesthesiology and Neuroscience, Washington University, School of Medicine, St Louis, MO, USA
b Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
 

Abstract
Recent advances in technology, including high resolution crystal structures of opioid receptors, novel chemical tools, and new genetic approaches have provided an unparalleled palette of tools for deconstructing opioid receptor actions in vitro and in vivo. Here we provide a brief description of our understanding of opioid receptor function from both molecular and atomic perspectives, as well as their role in neural circuits in vivo. We then show how insights into the molecular details of opioid actions can facilitate the creation of functionally selective (biased) and photoswitchable opioid ligands. Finally, we describe how newly engineered opioid receptor-based chemogenetic and optogenetic tools, and new mouse lines, are expanding and transforming our understanding of opioid function and, perhaps, paving the way for new therapeutics. Crystal structures of the inactive states for all four receptors (μ, δ, κ, and nociceptin) and the active state of μ have been elucidated and these structures are accelerating the structure-guided design of novel opioid ligands.Functionally selective, or biased, opioid ligands for several opioid receptors exist and hold promise as improved therapeutics with fewer liabilities.New chemogenetic and optogenetic opioid receptors hold promise for transforming basic and translational opioid receptor research.Genetically engineered mice and photocaged opioid ligands allow unprecedented spatiotemporal control of opioid receptors, opioid peptide release, and opioid ligand expression. © 2016 Elsevier Ltd.
 

Author Keywords
Biased signaling;  Chemogenetics;  DREADDs;  Functional selectivity;  Mouse models;  Optogenetics
 


Document Type: Article in Press
Source: Scopus
 



 

Rogers, C.E.a b , Smyser, T.a , Smyser, C.D.b c , Shimony, J.d , Inder, T.E.e , Neil, J.J.f
Regional white matter development in very preterm infants: Perinatal predictors and early developmental outcomes
(2016) Pediatric Research, 79 (1), pp. 87-95. 

DOI: 10.1038/pr.2015.172
 

a Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
b Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
c Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
d Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, United States
e Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, United States
f Department of Neurology, Boston Children's Hospital, Boston, MA, United States
 

Abstract
Background:Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes.Methods:Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30 wk gestation imaged up to four times from 26-42 wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age.Results:FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle.Conclusion:This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates. © 2016 International Pediatric Research Foundation, Inc.
 
 


Document Type: Article
Source: Scopus
 



 

Tomasian, A., Wallace, A., Northrup, B., Hillen, T.J., Jennings, J.W.
Spine cryoablation: Pain palliation and local tumor control for vertebral metastases
(2016) American Journal of Neuroradiology, 37 (1), pp. 189-195. 

DOI: 10.3174/ajnr.A4521
 

Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd, St Louis, MO, United States
 

Abstract
BACKGROUND AND PURPOSE: Percutaneous cryoablation has emerged as a minimally invasive technique for the management of osseous metastases. The purpose of this study was to assess the safety and effectiveness of percutaneous imaging-guided spine cryoablation for pain palliation and local tumor control for vertebral metastases. MATERIALS AND METHODS: Imaging-guided spine cryoablation was performed in 14 patients (31 tumors) with vertebral metastases refractory to conventional chemoradiation therapy or analgesics, to achieve pain palliation and local tumor control in this retrospective study. Spinal nerve and soft-tissue thermal protection techniques were implemented in all ablations. Patient response was evaluated by a pain numeric rating scale administered before the procedure and 1 week, 1 month, and 3 months after the procedure. Pre- and postprocedural analgesic requirements (expressed as morphine-equivalent dosages) were also analyzed at the same time points. Pre- and postprocedural cross-sectional imaging was evaluated in all patients to assess local control (no radiographic evidence of disease at the treated sites). Complications were monitored. Analysis of the primary end points was undertaken via paired-comparison procedures by using the Wilcoxon signed rank test. RESULTS: Thirty-one tumors were ablated in 14 patients (9 women and 5 men; 20-73 years of age; mean age, 53 years). The most common tumor location was in the lumbar spine (n = 14, 45%), followed by the thoracic spine (n = 8, 26%), sacrum (n = 6, 19%), coccyx (n = 2, 6%), and cervical spine (n = 1, 3%). There were statistically significant decreases in the median numeric rating scale score and analgesic usage at 1-week, 1-month, and 3-month time points (P < .001 for all). Local tumor control was achieved in 96.7% (30/31) of tumors (median follow-up, 10 months). Two patients had transient postprocedural unilateral lower extremity radiculopathy and weakness. CONCLUSIONS: Percutaneous imaging-guided spine cryoablation is a safe and effective treatment for pain palliation and local tumor control for vertebral metastases. © 2016, American Society of Neuroradiology. All rights reserved.
 
 


Document Type: Article
Source: Scopus
 



 

Fountoulakis, K.N.a , Gonda, X.b c , Koufaki, I.a , Hyphantis, T.d , Cloninger, C.R.e
The Role of Temperament in the Etiopathogenesis of Bipolar Spectrum Illness
(2016) Harvard Review of Psychiatry, 24 (1), pp. 36-52. 

DOI: 10.1097/HRP.0000000000000077
 

a 3rd Department of Psychiatry, School OfMedicine, Aristotle University of Thessaloniki, 6, Odysseos str, Pylaia Thessaloniki, Greece
b Departments of Clinical and Theoretical Mental Health, Kutvolgyi Clinical Center, Semmelweis University, Hungary
c Hungarian Academy of Science, Semmelweiss University Neuropsychopharmacology and Neurochemistry Research Group, Budapest, Hungary
d Department of Psychiatry, School of Medicine, University of Ioannina, Greece
e Department of Psychiatry, School of Medicine, Washington University, St. Louis, United States
 

Abstract
Bipolar disorder constitutes a challenge for clinicians in everyday clinical practice. Our knowledge concerning this clinical entity is incomplete, and contemporary classification systems are unable to reflect the complexity of this disorder. The concept of temperament, which was first described in antiquity, provides a helpful framework for synthesizing our knowledge on how the human body works and what determines human behavior. Although the concept of temperament originally included philosophical and sociocultural approaches, the biomedical model is dominant today. It is possible that specific temperaments might constitute vulnerability factors, determine the clinical picture, or modify the course of illness. Temperaments might even act as a bridge between genes and clinical manifestations, thus giving rise to the concept of the bipolar spectrum, with major implications for mental health research and treatment. More specifically, it has been reported that the hyperthymic and the depressive temperaments are related to the more "classic" bipolar disorder, whereas cyclothymic, anxious, and irritable temperaments are related to more complex manifestations and might predict poor response to treatment, violent or suicidal behavior, and high comorbidity. Incorporating of the concept of temperament and the bipolar spectrum into the standard training of psychiatric residents might well result in an improvement of everyday clinical practice. © 2016 President and Fellows of Harvard College.
 

Author Keywords
affective disorders;  affective temperaments;  bipolar spectrum illness;  etiopathogenesis;  temperaments
 


Document Type: Review
Source: Scopus
 



 

Jiang, X., Ory, D.S.
Towards a New Diagnostic Standard for Niemann-Pick C Disease
(2016) EBioMedicine, . Article in Press. 

DOI: 10.1016/j.ebiom.2016.01.004
 

Diabetic Cardiovascular Disease Center, Washington University, St. Louis, MO USA
 
 
 


Document Type: Article in Press
Source: Scopus
 



 

Vila, P.M., Schneider, J.S., Piccirillo, J.F., Lieu, J.E.C.
Understanding quality measures in otolaryngology-head and neck surgery
(2016) JAMA Otolaryngology - Head and Neck Surgery, 142 (1), pp. 86-90. 

DOI: 10.1001/jamaoto.2015.2687
 

Department of Otolaryngology-Head and Neck Surgery, Washington University, School of Medicine in St Louis, 660 S Euclid Ave, St Louis, MO, United States
 

Abstract
As health care reimbursements based on pay-for-performance models become more common, there is an unprecedented demand for ways to measure health care quality and demonstrate value. Performance measures, a type of quality measure, are unique tools in a health care delivery system that allow objective monitoring of adherence to specific goals and tracking of outcomes.We sought to provide information on the development of quality measures in otolaryngology-head and neck surgery, as well as the goals of performance measurement at a national level and for our specialty. The historical development, various types, and approach to creating effective performance measures are discussed. The primary methods of developing performance measures (using clinical practice guidelines, clinical registries, and alternativemethods) are also discussed. Performance measures are an important tool that can aid otolaryngologists in achieving effective, efficient, equitable, timely, safe, and patient-centered care as outlined by the Institute of Medicine. Copyright 2016 American Medical Association. All rights reserved.
 
 


Document Type: Review
Source: Scopus
 



 

Crockett, T.a , Wright, N.a , Thornquist, S.a , Ariel, M.b , Wessel, R.a
Turtle dorsal cortex pyramidal neurons comprise two distinct cell types with indistinguishable visual responses
(2015) PLoS ONE, 10 (12), art. no. 0144012, . 

DOI: 10.1371/journal.pone.0144012
 

a Department of Physics, Washington University in St. Louis, St. Louis, MO, United States
b Department of Pharmacology and Physiology, Saint Louis University, School of Medicine, St. Louis, MO, United States
 

Abstract
A detailed inventory of the constituent pieces in cerebral cortex is considered essential to understand the principles underlying cortical signal processing. Specifically, the search for pyramidal neuron subtypes is partly motivated by the hypothesis that a subtype-specific division of labor could create a rich substrate for computation. On the other hand, the extreme integration of individual neurons into the collective cortical circuit promotes the hypothesis that cellular individuality represents a smaller computational role within the context of the larger network. These competing hypotheses raise the important question to what extent the computational function of a neuron is determined by its individual type or by its circuit connections. We created electrophysiological profiles from pyramidal neurons within the sole cellular layer of turtle visual cortex by measuring responses to current injection using whole-cell recordings. A blind clustering algorithm applied to these data revealed the presence of two principle types of pyramidal neurons. Brief diffuse light flashes triggered membrane potential fluctuations in those same cortical neurons. The apparently network driven variability of the visual responses concealed the existence of subtypes. In conclusion, our results support the notion that the importance of diverse intrinsic physiological properties is minimized when neurons are embedded in a synaptic recurrent network. © 2015 Crockett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
 


Document Type: Article
Source: Scopus
 



 

Hoseini, M.S., Wessel, R.
Coherent and intermittent ensemble oscillations emerge from networks of irregular spiking neurons
(2015) Journal of Neurophysiology, 115 (1), pp. 457-469. 

DOI: 10.1152/jn.00578.2015
 

Department of Physics, Washington University, St. Louis, MO, United States
 

Abstract
Local field potential (LFP) recordings from spatially distant cortical circuits reveal episodes of coherent gamma oscillations that are intermittent, and of variable peak frequency and duration. Concurrently, single neuron spiking remains largely irregular and of low rate. The underlying potential mechanisms of this emergent network activity have long been debated. Here we reproduce such intermittent ensemble oscillations in a model network, consisting of excitatory and inhibitory model neurons with the characteristics of regular-spiking (RS) pyramidal neurons, and fast-spiking (FS) and lowthreshold spiking (LTS) interneurons. We find that fluctuations in the external inputs trigger reciprocally connected and irregularly spiking RS and FS neurons in episodes of ensemble oscillations, which are terminated by the recruitment of the LTS population with concurrent accumulation of inhibitory conductance in both RS and FS neurons. The model qualitatively reproduces experimentally observed phase drift, oscillation episode duration distributions, variation in the peak frequency, and the concurrent irregular single-neuron spiking at low rate. Furthermore, consistent with previous experimental studies using optogenetic manipulation, periodic activation of FS, but not RS, model neurons causes enhancement of gamma oscillations. In addition, increasing the coupling between two model networks from low to high reveals a transition from independent intermittent oscillations to coherent intermittent oscillations. In conclusion, the model network suggests biologically plausible mechanisms for the generation of episodes of coherent intermittent ensemble oscillations with irregular spiking neurons in cortical circuits. © 2016 the American Physiological Society.
 

Author Keywords
Coherence;  Cortex;  Intermittent;  γ-band oscillation
 


Document Type: Article
Source: Scopus
 



 

Pahwa, M.a , Kusner, M.b , Hacker, C.D.a c , Bundy, D.T.a , Weinberger, K.Q.b , Leuthardt, E.C.a c d e
Optimizing the detection of wakeful and sleep-like states for future electrocorticographic brain computer interface applications
(2015) PLoS ONE, 10 (11), art. no. e0142947, . 

DOI: 10.1371/journal.pone.0142947
 

a Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
b Department of Computer Science and Engineering, Washington University, St. Louis, MO, United States
c School of Medicine, Washington University, St. Louis, MO, United States
d Department of Neurological Surgery, Washington University, St. Louis, MO, United States
e Center for Innovation in Neuroscience and Technology, Washington University, St. Louis, MO, United States
 

Abstract
Previous studies suggest stable and robust control of a brain-computer interface (BCI) can be achieved using electrocorticography (ECoG). Translation of this technology from the laboratory to the real world requires additional methods that allow users operate their ECoGbased BCI autonomously. In such an environment, users must be able to perform all tasks currently performed by the experimenter, including manually switching the BCI system on/off. Although a simple task, it can be challenging for target users (e.g., individuals with tetraplegia) due to severe motor disability. In this study, we present an automated and practical strategy to switch a BCI system on or off based on the cognitive state of the user. Using a logistic regression, we built probabilistic models that utilized sub-dural ECoG signals from humans to estimate in pseudo real-time whether a person is awake or in a sleep-like state, and subsequently, whether to turn a BCI system on or off. Furthermore, we constrained these models to identify the optimal anatomical and spectral parameters for delineating states. Other methods exist to differentiate wake and sleep states using ECoG, but none account for practical requirements of BCI application, such as minimizing the size of an ECoG implant and predicting states in real time. Our results demonstrate that, across 4 individuals, wakeful and sleep-like states can be classified with over 80% accuracy (up to 92%) in pseudo real-time using high gamma (70-110 Hz) band limited power from only 5 electrodes (platinum discs with a diameter of 2.3 mm) located above the precentral and posterior superior temporal gyrus. © 2015 Pahwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
 


Document Type: Article
Source: Scopus
 



 

Abdelmalek, D.a , Arroyo-Plasencia, A.b , Schwarz, E.S.c , Weber, J.d , Sampson, C.S.e , Thornton, S.L.f , Mullins, M.E.g
Factitious snake envenomation and narcotic-seeking behavior
(2015) The American journal of emergency medicine, 33 (9), pp. 1331.e5-6. 

DOI: 10.1016/j.ajem.2015.03.020
 

a Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA
b Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA
c Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA
d Missouri Regional Poison Center, SSM Cardinal Glennon Children's Hospital, St. Louis, MO, USA
e Department of Emergency Medicine, University of Missouri School of Medicine, Columbia, MO, USA
f Department of Emergency Medicine University of Kansas School of Medicine, Kansas City, KS, USA
g Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mullinsm@wusm.wustl.edu
 
 
 


Document Type: Article
Source: Scopus
 



 

Jeong, J.-W.a , McCall, J.G.b , Zhang, Y.c , Huang, Y.c , Bruchas, M.R.b , Rogers, J.A.d
Soft microfluidic neural probes for wireless drug delivery in freely behaving mice
(2015) 2015 Transducers - 2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS 2015, art. no. 7181413, pp. 2264-2267. 

DOI: 10.1109/TRANSDUCERS.2015.7181413
 

a Department of Electrical, Computer and Energy Engineering, University of Colorado, Boulder, CO, United States
b Department of Anatomy-Neurobiology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Mechanical Engineering, Northwestern University, Evanston, IL, United States
d Department of Materials Science and Engineering, University of Illinois, Urbana-Champaign, IL, United States
 

Abstract
We present ultrathin, soft microfluidic neural probes with wireless drug delivery capability that can be injected precisely in the deep brain tissue. These probes permit targeted, wireless, spatiotemporal control of pharmacological manipulation in freely behaving mice. Because of the flexible, wireless nature of this probe, it is minimally invasive and has potential for broad applications in neuroscience as well as clinical medicine. © 2015 IEEE.
 

Author Keywords
drug delivery;  flexible neural probe;  freely behaving mice;  neuroscience;  soft;  Wireless microfluidics
 


Document Type: Conference Paper
Source: Scopus
 



 

Maccotta, L.a , Vega, C.b , Hogan, R.E.a , Waterhouse, E.c , Louis, E.K.S.d , Enke, A.M.e , Dunn, D.W.f , Kronenberger, W.G.f , Smith, M.g , Park, E.L.g
Causes and types of cognitive domain impairments in epilepsy
(2015) Epilepsy and the Interictal State: Co-morbidities and Quality of Life, pp. 28-73. 

DOI: 10.1002/9781118951026.ch4
 

a Comprehensive Epilepsy Center, Barnes Jewish Hospital and Washington University, United States
b Division of Epilepsy and Clinical Neurophysiology, Children's Hospital Boston and Harvard University, United States
c Department of Neurology, Virginia Commonwealth University School of Medicine, United States
d Department of Neurology, Mayo Clinic, United States
e Creighton University, United States
f Department of Psychiatry and Neurology, Indiana University School of Medicine, United States
g Rush Epilepsy Center, Rush University Medical Center, United States
 
 
 


Document Type: Book Chapter
Source: Scopus
 



 

Anticevic, A.a b c , Murray, J.D.d , Barch, D.M.e
Bridging Levels of Understanding in Schizophrenia Through Computational Modeling
(2015) Clinical Psychological Science, 3 (3), pp. 433-459. Cited 1 time.

DOI: 10.1177/2167702614562041
 

a Department of Psychiatry, Yale University, United States
b National Institute on Alcohol Abuse and Alcoholism Center for the Translational Neuroscience of Alcoholism, New Haven, CT, United States
c Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, United States
d Center for Neural Science, New York University, United States
e Department of Psychology and Department of Psychiatry, Washington University in St. Louis, United States
 

Abstract
Schizophrenia is an illness with a remarkably complex symptom presentation that has thus far been out of reach of neuroscientific explanation. This presents a fundamental problem for developing better treatments that target specific symptoms or root causes. One promising path forward is the incorporation of computational neuroscience, which provides a way to formalize experimental observations and, in turn, make theoretical predictions for subsequent studies. We review three complementary approaches: (a) biophysically based models developed to test cellular-level and synaptic hypotheses, (b) connectionist models that give insight into large-scale neural-system-level disturbances in schizophrenia, and (c) models that provide a formalism for observations of complex behavioral deficits, such as negative symptoms. We argue that harnessing all of these modeling approaches represents a productive approach for better understanding schizophrenia. We discuss how blending these approaches can allow the field to progress toward a more comprehensive understanding of schizophrenia and its treatment. © 2015, © The Author(s) 2015.
 

Author Keywords
cognitive deficits;  computational modeling;  schizophrenia;  symptoms;  systems neuroscience
 


Document Type: Review
Source: Scopus

 

 

February 5, 2016 

Fox, J.M.a , Fernandez, K.C.a , Rodebaugh, T.L.a , Menatti, A.R.b , Weeks, J.W.b
Investigating stereotypes of social anxiety
(2016) Anxiety, Stress and Coping, 29 (2), pp. 173-186. 

DOI: 10.1080/10615806.2015.1035999


a Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychology, Ohio University, Athens, OH, United States


Abstract
Background and Objectives: This paper consists of two studies that test for the presence and content of stereotypes of highly socially anxious individuals. Design: The current studies examined traits that comprise social anxiety stereotypes, and then tested whether undergraduate students held part of this stereotype via an implicit-association test (IAT). Methods: In Study 1, a sample of undergraduate students (n = 635) was asked to generate descriptors of people who are highly socially anxious. These descriptors were utilized to create the Social Anxiety Stereotype Measure (SASM) and the underlying factor structure of the SASM was analyzed. In Study 2, a different sample of undergraduate students (n = 87) was given an IAT to further test for the presence of one of the factors obtained in Study 1. Results: Factor analyses indicated the presence of two social anxiety stereotypes: social inhibition and oddity (comparative fit index =.97, Tucker-Lewis Index =.95, root mean square error of approximation =.07, standardized root mean square residual =.06). Oddity as a stereotype of social anxiety was further supported via an IAT: Participants reacted more quickly when oddity (vs. normality) words were paired with social anxiety (vs. social confidence) words (D = −1.15, SD =.26; t(85) = −41.50, p <.001). Conclusions: Factor analyses revealed two social anxiety stereotypes: social inhibition and oddity. Further testing of the oddity stereotype was supported via an IAT. © 2015 Taylor & Francis.


Author Keywords
implicit-association test (IAT);  oddity;  social anxiety;  social anxiety disorder;  social inhibition;  stereotype


Document Type: Article
Source: Scopus




Rucker, J.J.H.a e , Tansey, K.E.a c , Rivera, M.a p , Pinto, D.b q , Cohen-Woods, S.a , Uher, R.a h , Aitchison, K.J.a n , Craddock, N.c , Owen, M.J.c , Jones, L.o , Jones, I.c , Korszun, A.f , Barnes, M.R.d , Preisig, M.g , Mors, O.m , Maier, W.i , Rice, J.j , Rietschel, M.k , Holsboer, F.l , Farmer, A.E.a e , Craig, I.W.a , Scherer, S.W.b r , McGuffin, P.a e , Breen, G.a e
Phenotypic association analyses with copy number variation in recurrent depressive disorder
(2016) Biological Psychiatry, 79 (4), pp. 329-336. 

DOI: 10.1016/j.biopsych.2015.02.025


a Medical Research Council Social Genetic and Developmental Psychiatry Centre, PO80, Institute of Psychiatry, King's College London, London, United Kingdom
b Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON, Canada
c Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom
d GlaxoSmithKline, Verona, Italy
e National Institute for Health Research Biomedical Research Centre, Institute of Psychiatry, King's College London, United Kingdom
f Barts and the London School of Medicine and Denistry, Queen Mary University of London, London, United Kingdom
g Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland
h Department of Psychiatry, Dalhousie University, Halifax, NS, Canada
i Department of Psychiatry, University of Bonn, Bonn, Germany
j Department of Psychiatry, Washington University, St Louis, MO, United States
k Central Institute of Mental Health, Mannheim, Germany
l Max Planck Institute of Psychiatry, Munich, Germany
m Centre of Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
n Department of Psychiatry, University of Alberta, Edmonton, AB, Canada
o Department of Psychiatry, University of Birmingham, Birmingham, United Kingdom
p Section of Psychiatry, Institute of Neurosciences, University of Granada, Granada, Spain
q Departments of Psychiatry and Genetics and Genomic Sciences, Seaver Autism Center, Mount Sinai School of Medicine, New York, NY, United States
r McLaughlin Centre, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada


Abstract
Background Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. Methods In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. Results We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p =.023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p =.0002). Conclusions After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders. © 2016 Society of Biological Psychiatry.


Author Keywords
Affective disorders;  Copy number variation;  Depression;  Genetics;  Phenotypes


Document Type: Article
Source: Scopus




Duma, A.a , Pal, S.a , Helsten, D.a , Stein, P.K.b , Miller, J.P.c , Nagele, P.a
High-fidelity analysis of perioperative QTc prolongation
(2016) Anesthesia and Analgesia, 122 (2), pp. 439-448. 

DOI: 10.1213/ANE.0000000000001023


a Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States
b Cardiovascular Division, Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, United States
c Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States


Abstract
BACKGROUND: Prolongation of the QTc interval indicates abnormal cardiac repolarization. A recent study has shown that postoperative QTc prolongation is common. However, it is unknown whether QTc prolongation is an isolated postoperative phenomenon or occurs regularly during surgery, or whether the type of anesthesia influences its incidence. METHODS: To answer this question, we conducted a prospective cohort study (n = 300), where QTc duration was continuously recorded by 12-lead Holter electrocardiogram from 30 minutes preoperatively to up to 60 minutes postoperatively. QTc prolongation was compared between adult patients with at least 1 cardiac risk factor undergoing general (n = 101) or spinal anesthesia (n = 99) for orthopedic surgery, or local anesthesia (n = 100). Primary outcome was intraoperative QTc increase (ΔQTc, as defined by the intraoperative-to-preoperative QTc duration difference). The incidence of long QTc episodes (QTc > 500 milliseconds for at least 15 minutes) was also determined. RESULTS: Significant QTc prolongation (median; interquartile range [IQR]) occurred during general anesthesia (ΔQTc, +33 milliseconds; IQR, +22 to 46 milliseconds) and spinal anesthesia (ΔQTc, +22 milliseconds; IQR, +12 to 29 milliseconds), whereas no QTc prolongation was observed during local anesthesia (biopsy, n = 53: ΔQTc, +4 milliseconds; IQR, -4 to +7 milliseconds; coronary angiography, n = 47: ΔQTc, +6 milliseconds; IQR, -5 to +16 milliseconds). The incidence of long QTc episodes was significantly different between general anesthesia (n = 6/63, 9.5%), spinal anesthesia (n = 1/56, 1.8%), local anesthesia for biopsy (n = 0/46, 0%), and coronary angiography (n = 0/19, 0%; P = 0.045). CONCLUSIONS: These results indicate that QTc prolongation is not an isolated postoperative phenomenon and is common during surgery under general and spinal anesthesia. © 2016 International Anesthesia Research Society.


Document Type: Article
Source: Scopus




Kurhade, C.a , Zegenhagen, L.b , Weber, E.a g , Nair, S.b h , Michaelsen-Preusse, K.c , Spanier, J.d , Gekara, N.O.e , Kröger, A.b f , Överby, A.K.a
Type I Interferon response in olfactory bulb, the site of tick-borne flavivirus accumulation, is primarily regulated by IPS-1
(2016) Journal of Neuroinflammation, . Article in Press. 

DOI: 10.1186/s12974-016-0487-9


a Virology, Department of Clinical Microbiology, Umeå University, Umeå
b Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig
c Department of Cellular Neurobiology, Technical University Braunschweig, Braunschweig
d Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover Medical School and Helmholtz Centre for Infection Research, Hannover
e Department of Molecular Biology, Umeå University, Umeå
f Institute of Medical Microbiology, Otto-von-Guericke-University Magdeburg, Magdeburg
g Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn
h Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO


Abstract
Background: Although type I interferons (IFNs)-key effectors of antiviral innate immunity are known to be induced via different pattern recognition receptors (PRRs), the cellular source and the relative contribution of different PRRs in host protection against viral infection is often unclear. IPS-1 is a downstream adaptor for retinoid-inducible gene I (RIG-I)-like receptor signaling. In this study, we investigate the relative contribution of IPS-1 in the innate immune response in the different brain regions during infection with tick-borne encephalitis virus (TBEV), a flavivirus that causes a variety of severe symptoms like hemorrhagic fevers, encephalitis, and meningitis in the human host. Methods: IPS-1 knockout mice were infected with TBEV/Langat virus (LGTV), and viral burden in the peripheral and the central nervous systems, type I IFN induction, brain infiltrating cells, and inflammatory response was analyzed. Results: We show that IPS-1 is indispensable for controlling TBEV and LGTV infections in the peripheral and central nervous system. Our data indicate that IPS-1 regulates neuropathogenicity in mice. IFN response is differentially regulated in distinct regions of the central nervous system (CNS) influencing viral tropism, as LGTV replication was mainly restricted to olfactory bulb in wild-type (WT) mice. In contrast to the other brain regions, IFN upregulation in the olfactory bulb was dependent on IPS-1 signaling. IPS-1 regulates basal levels of antiviral interferon-stimulated genes (ISGs) like viperin and IRF-1 which contributes to the establishment of early viral replication which inhibits STAT1 activation. This diminishes the antiviral response even in the presence of high IFN-β levels. Consequently, the absence of IPS-1 causes uncontrolled virus replication, in turn resulting in apoptosis, activation of microglia and astrocytes, elevated proinflammatory response, and recruitment of inflammatory cells into the CNS. Conclusions: We show that LGTV replication is restricted to the olfactory bulb and that IPS-1 is a very important player in the olfactory bulb in shaping the innate immune response by inhibiting early viral replication and viral spread throughout the central nervous system. In the absence of IPS-1, higher viral replication leads to the evasion of antiviral response by inhibiting interferon signaling. Our data suggest that the local microenvironment of distinct brain regions is critical to determine virus permissiveness. © 2016 Kurhade et al.


Author Keywords
Antiviral mechanism;  Brain;  Immune evasion;  IPS-1;  Olfactory bulb;  Tick-borne encephalitis;  Type I interferons


Document Type: Article in Press
Source: Scopus




Qaddoumi, I.a , Orisme, W.b , Wen, J.b , Santiago, T.b , Gupta, K.b , Dalton, J.D.b , Tang, B.b , Haupfear, K.b , Punchihewa, C.b , Easton, J.c , Mulder, H.c , Boggs, K.c , Shao, Y.c , Rusch, M.c , Becksfort, J.c , Gupta, P.c , Wang, S.c , Lee, R.P.b , Brat, D.d , Peter Collins, V.e , Dahiya, S.f , George, D.g , Konomos, W.h , Kurian, K.M.i , McFadden, K.j , Serafini, L.N.k , Nickols, H.l , Perry, A.m , Shurtleff, S.b , Gajjar, A.a , Boop, F.A.n , Klimo, P.D., Jr.n , Mardis, E.R.f , Wilson, R.K.f , Baker, S.J.o , Zhang, J.c , Wu, G.c , Downing, J.R.b , Tatevossian, R.G.b , Ellison, D.W.b
Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology
(2016) Acta Neuropathologica, pp. 1-13. Article in Press. 

DOI: 10.1007/s00401-016-1539-z


a Department of Oncology, St. Jude Children’s Research Hospital, Memphis, United States
b Department of Pathology, St. Jude Children’s Research Hospital, Memphis, United States
c Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, United States
d Department of Pathology, Emory University School of Medicine, Atlanta, United States
e Department of Pathology, University of Cambridge, Cambridge, United Kingdom
f Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States
g Department of Pathology, Foothills Medical Center, Las Cruces, United States
h Department of Pathology, Innovative Pathology Services Knoxville, Knoxville, United States
i Department of Pathology, Frenchay Hospital, Bristol, United Kingdom
j Department of Pathology, University of Pittsburgh, Pittsburgh, United States
k Department of Pathology, University of São Paulo, Ribeirão Preto School of Medicine, São Paulo, Brazil
l Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, United States
m Department of Pathology, University of California, San Francisco, San Francisco, United States
n Department of Surgery, St. Jude Children’s Research Hospital, Memphis, United States
o Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, United States


Abstract
Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and ‘adult-type’ diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n = 22), diffuse oligodendroglial tumors (d-OTs; n = 20), diffuse astrocytomas (DAs; n = 17), angiocentric gliomas (n = 15), and gangliogliomas (n = 17). Most LGNTs (84 %) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte-like cells, being present in 82 % of DNETs and 40 % of d-OTs. In contrast, a MYB-QKI fusion characterized almost all angiocentric gliomas (87 %), and MYB fusion genes were the most common genetic alteration in DAs (41 %). A BRAF:p.V600E mutation was present in 35 % of gangliogliomas and 18 % of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78 % of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials. © 2016 Springer-Verlag Berlin Heidelberg


Author Keywords
BRAF;  FGFR1;  Glioma;  Glioneuronal;  MYB;  RNA-seq


Document Type: Article in Press
Source: Scopus




Carpenter, B.D.a , Sakai, E.a , Karel, M.J.b , Molinari, V.c , Moye, J.d
Training for Research and Teaching in Geropsychology: Preparing the Next Generation of Scholars and Educators
(2016) Gerontology and Geriatrics Education, pp. 1-19. Article in Press. 

DOI: 10.1080/02701960.2015.1115981


a Department of Psychology, Washington University, St. Louis, Missouri, USA
b Mental Health Services, Department of Veteran Affairs Central Office, Washington DC, USA
c School of Aging Studies, University of South Florida, Tampa, Florida, USA
d VA Boston Healthcare System and Harvard Medical School, Brockton, Massachusetts, USA


Abstract
For geropsychology to flourish in the years ahead, we need scientists to advance knowledge and teachers to draw new professionals into the field. In this project the authors surveyed 100 geropsychologists who completed a doctoral degree in clinical or counseling psychology about their experience with training for research and teaching. The majority were currently conducting some degree of research (38%) and some form of teaching (45%). The majority of ratings for components of research training were in the “very good to excellent” range, whereas elements of teacher training were rated in the “poor to good” range, though there was variability among persons and components. Qualitative comments revealed enthusiasm for research and teaching roles and a need to enhance our training of geropsychologists as educators. The authors provide several suggestions that could enhance research and teacher training for current and future students of professional geropsychology. © 2016, Routledge. All rights reserved.


Author Keywords
aging;  education;  science


Document Type: Article in Press
Source: Scopus




Hou, P.a d , Xiao, F.b , Liu, H.a , Yuchi, M.b , Zhang, G.d , Wu, Y.a , Wang, W.a , Zeng, W.a , Ding, M.b , Cui, J.d e , Wu, Z.a , Wang, L.-Y.c , Ding, J.a
Extrapolating microdomain Ca2+ dynamics using BK channels as a Ca2+ sensor
(2016) Scientific Reports, 6, art. no. 17343, . 

DOI: 10.1038/srep17343


a Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China
b Key Laboratory of Image Processing and Intelligent Control, Huazhong University of Science and Technology, Ministry of Education, Department of Biomedical Engineering, College of Life Science and Technology, Wuhan, Hubei, China
c Program in Neurosciences and Mental Health, SickKids Research Institute, Department of Physiology, University of Toronto, Toronto, ON, Canada
d Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, MO, United States
e Department of Pharmacology, Soochow University College of Pharmaceutical Sciences, Suzhou, China


Abstract
Ca2+ ions play crucial roles in mediating physiological and pathophysiological processes, yet Ca2+ dynamics local to the Ca2+ source, either from influx via calcium permeable ion channels on plasmic membrane or release from internal Ca2+ stores, is difficult to delineate. Large-conductance calcium-activated K+ (BK-type) channels, abundantly distribute in excitable cells and often localize to the proximity of voltage-gated Ca2+ channels (VGCCs), spatially enabling the coupling of the intracellular Ca2+ signal to the channel gating to regulate membrane excitability and spike firing patterns. Here we utilized the sensitivity and dynamic range of BK to explore non-uniform Ca2+ local transients in the microdomain of VGCCs. Accordingly, we applied flash photolysis of caged Ca2+ to activate BK channels and determine their intrinsic sensitivity to Ca2+. We found that uncaging Ca2+ activated biphasic BK currents with fast and slow components (time constants being τf≈0.2 ms and τs≈10 ms), which can be accounted for by biphasic Ca2+ transients following light photolysis. We estimated the Ca2+-binding rate constant kb (≈1.8×108M-1s-1) for mSlo1 and further developed a model in which BK channels act as a calcium sensor capable of quantitatively predicting local microdomain Ca2+ transients in the vicinity of VGCCs during action potentials. © 2016, Nature Publishing Group. All rights reserved.


Document Type: Article
Source: Scopus




Pursley, A.J.a , Saunders, G.H.b
Knowledge, attitudes, behaviors, and noise exposure of baristas
(2016) International Journal of Audiology, pp. 1-5. Article in Press. 

DOI: 10.3109/14992027.2015.1124295


a Program in Audiology and Communication Sciences, Washington University School of Medicine, St. Louis, USA
b National Center for Rehabilitative Auditory Research (NCRAR), Portland VA Medical Center, Portland, USA


Abstract
Objective: To examine the daily noise exposure of baristas working in cafés, and to measure their knowledge, attitudes, and behaviors regarding hearing conservation and perceptions of noise in their work environment. Design: Fifteen baristas from six cafés in Portland completed the Knowledge, Attitudes and Behaviors questionnaire, a sound disturbance survey, and a structured interview to document perceptions of noise in the work environment. To measure daily noise exposure, a subset of eight participants wore a personal dosimeter for three different work shifts. Study sample: A total of 11 females and four males, aged between 19 and 36 years old (mean: 26.3, SD: 4.6) recruited from independently owned cafés in the Portland metro area. Results: Dosimetry measurements revealed Leq measurements between 71 and 83 dBA, with noise doses ranging from 4% to 74%, indicating that baristas are not exposed to sound levels above the regulatory criterion. Questionnaire results indicated that baristas have low awareness about the hazards of noise, are not opposed to hearing conservation, and rarely use hearing protection when engaged in noisy activities. Conclusions: Baristas here lacked the pertinent education and motivation to commit to invaluable hearing conservation practices. © 2016 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society


Document Type: Article in Press
Source: Scopus




Moreno, J.L.a b , Miranda-Azpiazu, P.c d , García-Bea, A.b c d , Younkin, J.a , Cui, M.a , Kozlenkov, A.b , Ben-Ezra, A.b , Voloudakis, G.b , Fakira, A.K.e , Baki, L.a , Ge, Y.f , Georgakopoulos, A.b , Morón, J.A.e l , Milligan, G.g , López-Giménez, J.F.g h , Robakis, N.K.b i j , Logothetis, D.E.a , Meana, J.J.c d k , González-Maeso, J.a b f j
Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia
(2016) Science Signaling, 9 (410), . Cited 1 time.

DOI: 10.1126/scisignal.aab0467


a Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States
b Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
c Department of Pharmacology, University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain
d Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain
e Department of Anesthesiology, Columbia University, College of Physicians and Sur., New York, NY, United States
f Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
g Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
h Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC-CSIC-UC), Santander, Cantabria, Spain
i Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
j Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
k BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain
l Department of Anesthesiology, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States


Abstract
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can form multiprotein complexes (heteromers), which can alter the pharmacology and functions of the constituent receptors. Previous findings demonstrated that the Gq/11-coupled serotonin 5-HT2A receptor and the Gi/o-coupled metabotropic glutamate 2 (mGlu2) receptor-GPCRs that are involved in signaling alterations associated with psychosis-assemble into a heteromeric complex in the mammalian brain. In single-cell experiments with various mutant versions of the mGlu2 receptor, we showed that stimulation of cells expressing mGlu2-5-HT2A heteromers with an mGlu2 agonist led to activation of Gq/11 proteins by the 5-HT2A receptors. For this crosstalk to occur, one of the mGlu2 subunits had to couple to G i/o proteins, and we determined the relative location of the Gi/o-contacting subunit within the mGlu2 homodimer of the heteromeric complex. Additionally, mGlu2-dependent activation of Gq/11, but not Gi/o, was reduced in the frontal cortex of 5-HT2A knockout mice and was reduced in the frontal cortex of postmortem brains from schizophrenic patients. These findings offer structural insights into this important target in molecular psychiatry.


Document Type: Article
Source: Scopus




Tajdaran, K.a b , Gordon, T.a c d , Wood, M.D.e , Shoichet, M.S.b f , Borschel, G.H.a b c d
An engineered biocompatible drug delivery system enhances nerve regeneration after delayed repair
(2016) Journal of Biomedical Materials Research - Part A, 104 (2), pp. 367-376. 

DOI: 10.1002/jbm.a.35572


a Division of Plastic and Reconstructive Surgery, Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada
b Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada
c Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada
d Program in Neuroscience, Hospital for Sick Children Research Institute, Toronto, ON, Canada
e Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, MO, United States
f Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada


Abstract
Localized drug delivery strategies could greatly benefit patients with peripheral nerve injury and could be easy for surgeons to implement. We developed a local drug delivery system (DDS) using drug-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) embedded in a fibrin gel. In an in vitro study, we investigated the biocompatibility of this DDS by performing a toxicity assay in which we incubated PC-12 cells with the medium released from the DDS in vitro. In an in vivo study, this DDS was applied at the rat common peroneal (CP) nerve injury site to deliver exogenous glial cell line-derived neurotrophic factor (GDNF) to the regenerating axons after delayed nerve repair. In vitro, PC-12 cells incubated with released media samples from the DDS had similar viability to control cells cultured with normal media, demonstrating that the DDS was not toxic. In vivo, the numbers of motor and sensory neurons that regenerated their axons with empty MS treatment were the same as when there was no MS treatment. The DDS increased the numbers of regenerating motor- and sensory neurons to levels indistinguishable from those observed with immediate nerve repair. The DDS increased neuron regeneration to levels double those observed with negative control groups. This biocompatible, nontoxic, fibrin gel-based DDS enhances outcomes following severe peripheral nerve injuries. © 2015 Wiley Periodicals, Inc.


Author Keywords
biomaterials;  chronic axotomy;  chronic denervation;  drug delivery;  glial cell line-derived neurotrophic factor;  nerve injury;  regenerative medicine


Document Type: Article
Source: Scopus




Tambini, M.D.a , Pera, M.b , Kanter, E.b , Yang, H.b , Guardia-Laguarta, C.c , Holtzman, D.d , Sulzer, D.b , Area-Gomez, E.b , Schon, E.A.b e
ApoE4 upregulates the activity of mitochondria-associated ER membranes
(2016) EMBO Reports, 17 (1), pp. 27-36. 

DOI: 10.15252/embr.201540614


a Integrated Program in Cellular, Molecular and Biomedical Studies, Columbia University Medical Center, New York, NY, United States
b Department of Neurology, Columbia University Medical Center, New York, NY, United States
c Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, United States
d Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University, School of Medicine, St. Louis, MO, United States
e Department of Genetics and Development, Columbia University Medical Center, New York, NY, United States


Abstract
In addition to the appearance of senile plaques and neurofibrillary tangles, Alzheimer's disease (AD) is characterized by aberrant lipid metabolism and early mitochondrial dysfunction. We recently showed that there was increased functionality of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM), a subdomain of the ER involved in lipid and cholesterol homeostasis, in presenilin-deficient cells and in fibroblasts from familial and sporadic AD patients. Individuals carrying the ε4 allele of apolipoprotein E (ApoE4) are at increased risk for developing AD compared to those carrying ApoE3. While the reason for this increased risk is unknown, we hypothesized that it might be associated with elevated MAM function. Using an astrocyte-conditioned media (ACM) model, we now show that ER-mitochondrial communication and MAM function - as measured by the synthesis of phospholipids and of cholesteryl esters, respectively - are increased significantly in cells treated with ApoE4-containing ACM as compared to those treated with ApoE3-containing ACM. Notably, this effect was seen with lipoprotein-enriched preparations, but not with lipid-free ApoE protein. These data are consistent with a role of upregulated MAM function in the pathogenesis of AD and may help explain, in part, the contribution of ApoE4 as a risk factor in the disease. Synopsis The reason why ApoE4 is a risk factor in Alzheimer's disease is unknown. This study shows that lipoproteins containing ApoE4, but not those containing ApoE3, upregulate the communication between ER and mitochondria at mitochondria-associated ER membranes (MAM), and may help explain, in part, the role of ApoE4 as a risk factor in the disease. ER-mitochondrial communication and MAM function are increased in cells treated with ApoE4-containing ACM ApoE4 exerts its effects on MAM when incorporated into lipoprotein particles, not as the free protein These findings suggest that ApoE4's role in AD is associated with perturbed cholesterol homeostasis. The reason why ApoE4 is a risk factor in Alzheimer's disease is unknown. This study shows that lipoproteins containing ApoE4, but not those containing ApoE3, upregulate the communication between ER and mitochondria at mitochondria-associated ER membranes (MAM), and may help explain, in part, the role of ApoE4 as a risk factor in the disease. © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license.


Author Keywords
ApoE;  cholesterol;  cholesteryl esters;  endoplasmic reticulum;  lipoproteins;  MAM;  mitochondria;  phospholipids


Document Type: Article
Source: Scopus




Astafiev, S.V., Zinn, K.L., Shulman, G.L., Corbetta, M.
Exploring the physiological correlates of chronic mild traumatic brain injury symptoms
(2016) NeuroImage: Clinical, 11, pp. 10-19. 

DOI: 10.1016/j.nicl.2016.01.004


Department of Neurology, Washington University in St. Louis, Campus Box 8225, 660 S. Euclid Ave, St. Louis, MO, United States


Abstract
We report on the results of a multimodal imaging study involving behavioral assessments, evoked and resting-state BOLD fMRI, and DTI in chronic mTBI subjects. We found that larger task-evoked BOLD activity in the MT+/LO region in extra-striate visual cortex correlated with mTBI and PTSD symptoms, especially light sensitivity. Moreover, higher FA values near the left optic radiation (OR) were associated with both light sensitivity and higher BOLD activity in the MT+/LO region. The MT+/LO region was localized as a region of abnormal functional connectivity with central white matter regions previously found to have abnormal physiological signals during visual eye movement tracking (Astafiev et al., 2015). We conclude that mTBI symptoms and light sensitivity may be related to excessive responsiveness of visual cortex to sensory stimuli. This abnormal sensitivity may be related to chronic remodeling of white matter visual pathways acutely injured. © 2016 The Authors.


Author Keywords
Behavioral assessments;  Diffusion tensor imaging;  MRI;  Traumatic brain injury


Document Type: Article
Source: Scopus




Scherrer, J.F.a b c , Salas, J.a b , Copeland, L.A.d e f , Stock, E.M.d e , Ahmedani, B.K.g , Sullivan, M.D.h , Burroughs, T.c , David Schneider, F.a , Bucholz, K.K.i , Lustman, P.J.i j
Prescription opioid duration, dose, and increased risk of depression in 3 large patient populations
(2016) Annals of Family Medicine, 14 (1), pp. 54-62. Cited 1 time.

DOI: 10.1370/afm.1885


a Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO, United States
b Harry S. Truman Veterans Administration Medical Center, Columbia, MO, United States
c Saint Louis University Center for Outcomes Research, St. Louis, MO, United States
d Center for Applied Health Research, Baylor Scott and White Health, Central Texas Veterans Health Care System, Temple, TX, United States
e Texas A and M Health Science Center, Bryan, TX, United States
f University of Texas Health Science Center, San Antonio, TX, United States
g Henry Ford Health System, Center for Health Policy and Health Services Research, Detroit, MI, United States
h Department of Psychiatry and Behavioral Health, University of Washington School of Medicine, Seattle, WA, United States
i Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
j The Bell Street Clinic, VA St. Louis Health Care System – John Cochran Division, St. Louis, MO, United States


Abstract
PURPOSE Recent results suggests the risk of a new onset of depression increases with longer duration of opioid analgesic use. It is unclear whether new-onset depression related to opioid analgesic use is a function of the dose prescribed or the duration of use or both. METHODS Using a retrospective cohort design, we collected patient data from 2000 to 2012 from the Veterans Health Administration (VHA), and from 2003 to 2012 from both Baylor Scott & White Health (BSWH) and the Henry Ford Health System (HFHS). Patients (70,997 VHA patients, 13,777 BSWH patients, and 22,981 HFHS patients) were new opioid users, aged 18 to 80 years, without a diagnosis of depression at baseline. Opioid analgesic use duration was defined as 1 to 30, 31 to 90, and more than 90 days, and morphine equivalent dose (MED) was defined as 1 to 50 mg/d, 51 to 100 mg/d, and greater than 100 mg/d of analgesic. Pain and other potential confounders were controlled for by inverse probability of treatment–weighted propensity scores. RESULTS New-onset depression after opioid analgesic use occurred in 12% of the VHA sample, 9% of the BSWH sample, and 11% of the HFHS sample. Compared with 1- to 30-day users, new-onset depression increased in those with longer opioid analgesic use. Risk of new-onset depression with 31 to 90 days of opioid analgesic use ranged from hazard ratio [HR] = 1.18 (95% CI, 1.10-1.25) in VHA to HR = 1.33 (95% CI, 1.16-1.52) in HFHS; in opioid analgesic use of more than 90 days, it ranged from HR = 1.35 (95% CI, 1.26-1.44) in VHA to HR = 2.05 (95% CI, 1.75-2.40) in HFHS. Dose was not significantly associated with a new onset of depression. CONCLUSIONS Opioid-related new onset of depression is associated with longer duration of use but not dose. Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression. Opioid analgesic use, not just pain, should be considered a potential source when patients report depressed mood. © 2016, Annals of Family Medicine, Inc. All rights reserved.


Author Keywords
Analgesics;  Cohort;  Depression;  Epidemiology;  Opioid


Document Type: Article
Source: Scopus




Huff, M.J.a , Weinsheimer, C.C.b , Bodner, G.E.b
Reducing the Misinformation Effect Through Initial Testing: Take Two Tests and Recall Me in the Morning?
(2016) Applied Cognitive Psychology, 30 (1), pp. 61-69. 

DOI: 10.1002/acp.3167


a Department of Psychology, Washington University in St. Louis, St. Louis, United States
b Department of Psychology, University of Calgary, Calgary, AB, Canada


Abstract
Initial retrieval of an event can reduce people's susceptibility to misinformation. We explored whether protective effects of initial testing could be obtained on final free recall and source-monitoring tests. After studying six household scenes (e.g.,a bathroom), participants attempted to recall items from the scenes zero, one, or two times. Immediately or after a 48-hour delay, non-presented items (e.g.,soap and toothbrush) were exposed zero, one, or four times through a social contagion manipulation in which participants reviewed sets of recall tests ostensibly provided by other participants. A protective effect of testing emerged on a final free recall test following the delay and on a final source-memory test regardless of delay. Taking two initial tests did not increase these protective effects. Determining whether initial testing will have protective (versus harmful) effects on memory has important practical implications for interviewing eyewitnesses. © 2016 John Wiley & Sons, Ltd.


Document Type: Article
Source: Scopus




Bugg, J.M.a , Smallwood, A.b
The next trial will be conflicting! Effects of explicit congruency pre-cues on cognitive control
(2016) Psychological Research, 80 (1), pp. 16-33. Cited 2 times.

DOI: 10.1007/s00426-014-0638-5


a Department of Psychology, Washington University in St. Louis, Campus Box 1125, One Brookings Dr., St. Louis, MO, United States
b Department of Psychology, DePauw University, Greencastle, United States


Abstract
The dual mechanisms of control account proposed a role for proactive and reactive mechanisms in minimizing or resolving interference in conflict tasks. Proactive mechanisms are activated in advance of stimulus onset and lead to preparatory biasing of attention in a goal-directed fashion. Reactive mechanisms are triggered post-stimulus onset. Using an explicit, trial-by-trial pre-cueing procedure in a 4-choice color-word Stroop task, we investigated effects of congruency pre-cues on cognitive control. Under conditions of stimulus uncertainty (i.e., each word was associated with multiple, equally probable responses), pre-cue benefits were observed on incongruent trials when cues were 100 % valid but not when they were 75 % valid. These benefits were selectively found at the longest cue-to-stimulus interval (2,000 ms), consistent with a preparation-dependent proactive control mechanism. By contrast, when a reactive strategy of switching attention to the irrelevant dimension to predict the single correlated response was viable, pre-cue benefits were observed on incongruent trials for all cue-to-stimulus intervals including the shortest that afforded only 500 ms to prepare. The findings (a) suggest a restricted role for the preparation-dependent biasing of attention via proactive control in response to explicit, trial-by-trial pre-cues while (b) highlighting strategies that lead to pre-cue benefits but which appear to reflect primarily reactive use of the information afforded by the pre-cues. We conclude that pre-cues, though available in advance of stimulus onset, may stimulate proactive or reactive minimization of interference. © 2014, Springer-Verlag Berlin Heidelberg.


Document Type: Article
Source: Scopus




Roland, L.T.a , Kallogjeri, D.a , Sinks, B.C.a , Rauch, S.D.b , Shepard, N.T.c , White, J.A.d , Goebel, J.A.a
Utility of an abbreviated dizziness questionnaire to differentiate between causes of vertigo and guide appropriate referral: A multicenter prospective blinded study
(2015) Otology and Neurotology, 36 (10), pp. 1687-1694. 

DOI: 10.1097/MAO.0000000000000884


a Department of Otolaryngology - Head and Neck Surgery, Washington University in St Louis, School of Medicine, St Louis, MO, United States
b Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, United States
c Division of Audiology, Mayo Clinic, Rochester, MN, United States
d Section of Vestibular and Balance Disorders, Head and Neck Institute, Cleveland Clinic, Cleveland, OH, United States


Abstract
Objective: Test performance of a focused dizziness questionnaire's ability to discriminate between peripheral and nonperipheral causes of vertigo. Study Design: Prospective multicenter. Setting: Four academic centers with experienced balance specialists. Patients: New dizzy patients. Interventions: A 32-question survey was given to participants. Balance specialists were blinded and a diagnosis was established for all participating patients within 6 months. Main Outcomes: Multinomial logistic regression was used to evaluate questionnaire performance in predicting final diagnosis and differentiating between peripheral and nonperipheral vertigo. Univariate and multivariable stepwise logistic regression were used to identify questions as significant predictors of the ultimate diagnosis. C-index was used to evaluate performance and discriminative power of the multivariable models. Results: In total, 437 patients participated in the study. Eight participants without confirmed diagnoses were excluded and 429 were included in the analysis. Multinomial regression revealed that the model had good overall predictive accuracy of 78.5% for the final diagnosis and 75.5% for differentiating between peripheral and nonperipheral vertigo. Univariate logistic regression identified significant predictors of three main categories of vertigo: peripheral, central, and other. Predictors were entered into forward stepwise multivariable logistic regression. The discriminative power of the final models for peripheral, central, and other causes was considered good as measured by c-indices of 0.75, 0.7, and 0.78, respectively. Conclusion: This multicenter study demonstrates a focused dizziness questionnaire can accurately predict diagnosis for patients with chronic/relapsing dizziness referred to outpatient clinics. Additionally, this survey has significant capability to differentiate peripheral from nonperipheral causes of vertigo and may, in the future, serve as a screening tool for specialty referral. Clinical utility of this questionnaire to guide specialty referral is discussed. © 2015 Otology & Neurotology, Inc.


Author Keywords
History;  Questionnaire;  Vertigo


Document Type: Article
Source: Scopus




Enright, J.M.a , Toomey, M.B.a , Sato, S.-Y.b , Temple, S.E.c , Allen, J.R.d , Fujiwara, R.e , Kramlinger, V.M.e , Nagy, L.D.e , Johnson, K.M.e , Xiao, Y.e , How, M.J.c , Johnson, S.L.d , Roberts, N.W.c , Kefalov, V.J.b , Peter Guengerich, F.e , Corbo, J.C.a
Cyp27c1 red-shifts the spectral sensitivity of photoreceptors by converting Vitamin A1 into A2
(2015) Current Biology, 25 (23), pp. 3048-3057. Cited 1 time.

DOI: 10.1016/j.cub.2015.10.018


a Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
c School of Biological Sciences, University of Bristol, Bristol, United Kingdom
d Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, United States


Abstract
Some vertebrate species have evolved means of extending their visual sensitivity beyond the range of human vision. One mechanism of enhancing sensitivity to long-wavelength light is to replace the 11-cis retinal chromophore in photopigments with 11-cis 3,4-didehydroretinal. Despite over a century of research on this topic, the enzymatic basis of this perceptual switch remains unknown. Here, we show that a cytochrome P450 family member, Cyp27c1, mediates this switch by converting vitamin A1 (the precursor of 11-cis retinal) into vitamin A2 (the precursor of 11-cis 3,4-didehydroretinal). Knockout of cyp27c1 in zebrafish abrogates production of vitamin A2, eliminating the animal's ability to red-shift its photoreceptor spectral sensitivity and reducing its ability to see and respond to near-infrared light. Thus, the expression of a single enzyme mediates dynamic spectral tuning of the entire visual system by controlling the balance of vitamin A1 and A2 in the eye. © 2015 Elsevier Ltd All rights reserved.


Document Type: Article
Source: Scopus




Mitra, A.a , Snyder, A.Z.a b , Tagliazucchi, E.c d , Laufs, H.d e , Raichle, M.E.a b
Propagated infra-slow intrinsic brain activity reorganizes across wake and slow wave sleep
(2015) eLife, 4 (NOVEMBER2015), art. no. e10781, . 

DOI: 10.7554/eLife.10781.001


a Department of Radiology, Washington University in St. Louis, St. Louis, United States
b Department of Neurology, Washington University in St. Louis, St. Louis, United States
c Institute for Medical Psychology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
d Department of Neurology, Brain Imaging Center, Goethe-Universität Frankfurt am Main, Frankfurt, Germany
e Department of Neurology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany


Abstract
Propagation of slow intrinsic brain activity has been widely observed in electrophysiogical studies of slow wave sleep (SWS). However, in human resting state fMRI (rs- fMRI), intrinsic activity has been understood predominantly in terms of zero-lag temporal synchrony (functional connectivity) within systems known as resting state networks (RSNs). Prior rs-fMRI studies have found that RSNs are generally preserved across wake and sleep. Here, we use a recently developed analysis technique to study propagation of infra-slow intrinsic blood oxygen level dependent (BOLD) signals in normal adults during wake and SWS. This analysis reveals marked changes in propagation patterns in SWS vs. wake. Broadly, ordered propagation is preserved within traditionally defined RSNs but lost between RSNs. Additionally, propagation between cerebral cortex and subcortical structures reverses directions, and intra-cortical propagation becomes reorganized, especially in visual and sensorimotor cortices. These findings show that propagated rs-fMRI activity informs theoretical accounts of the neural functions of sleep. © Mitra et al.


Document Type: Article
Source: Scopus




Hancock, D.B.a , Levy, J.L.b , Gaddis, N.C.b , Glasheen, C.a , Saccone, N.L.c , Page, G.P.d , Bierut, L.J.e , Kral, A.H.f , Johnson, E.O.g
Replication of ZNF804A gene variant associations with risk of heroin addiction
(2015) Genes, Brain and Behavior, 14 (8), pp. 635-640. 

DOI: 10.1111/gbb.12254


a Behavioral Health and Criminal Justice Division, United States
b Research Computing Division, RTI International, Research Triangle Park, NC, United States
c Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
d Center for Genomics in Public Health and Medicine, RTI International, Atlanta, GA, United States
e Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
f Behavioral Health and Criminal Justice Division, RTI International, San Francisco, CA, United States
g Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC, United States


Abstract
Heroin addiction is heritable, but few specific genetic variants have been reproducibly associated with this disease. The zinc finger protein 804A (ZNF804A) gene is a biologically plausible susceptibility gene for heroin addiction, given its function as a transcription factor in human brain. Novel associations of two common ZNF804A single nucleotide polymorphisms (SNPs), rs7597593 and rs1344706, with heroin addiction have been reported in Han Chinese. Both SNPs have also been implicated for regulating ZNF804A expression in human brain, including the addiction-relevant dorsolateral prefrontal cortex. In this independent replication study, we tested the rs7597593 and rs1344706 SNP genotypes and their corresponding haplotypes for association with heroin addiction using cases drawn from the Urban Health Study and population controls: total N = 10 757 [7095 European Americans (EAs) and 3662 African Americans (AAs)]. We independently replicated both ZNF804A SNP associations in EAs: the rs7597593-T (P = 0.016) and rs1344706-A (P = 0.029) alleles both being associated with increased risk of heroin addiction, consistent with the prior report. Neither SNP was associated in AAs alone, but meta-analysis across both ancestry groups resulted in significant associations for rs1344706-A [P = 0.016, odds ratio (95% confidence interval) = 1.13 (1.02-1.25)] and its haplotype with rs7597593-T [P = 0.0067, odds ratio (95% confidence interval) = 1.16 (1.04-1.29)]. By showing consistent associations across independent studies and diverse ancestry groups, our study provides evidence that these two ZNF804A SNPs and their risk haplotype are among the few replicable genetic associations with heroin addiction. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.


Author Keywords
Ancestry;  Genetic association study;  Haplotype;  Heroin;  Opioid;  Replication;  Rs1344706;  Rs7597593;  Urban Health Study;  ZNF804A


Document Type: Article
Source: Scopus




Alamilla, J.a , Granados-Fuentes, D.b , Aguilar-Roblero, R.c
The anterior paraventricular thalamus modulates neuronal excitability in the suprachiasmatic nuclei of the rat
(2015) European Journal of Neuroscience, 42 (10), pp. 2833-2842. 

DOI: 10.1111/ejn.13088


a CONACYT Research Fellow - Centro de Investigaciones Biomédicas de la Universidad de Colima, Colima, Mexico
b Department of Biology, Washington University, St Louis, MO, United States
c División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-253, México, DF, Mexico


Abstract
The suprachiasmatic nucleus (SCN) in mammals is the master clock which regulates circadian rhythms. Neural activity of SCN neurons is synchronized to external light through the retinohypothalamic tract (RHT). The paraventricular thalamic nucleus (PVT) is a neural structure that receives synaptic inputs from, and projects back to, the SCN. Lesioning the anterior PVT (aPVT) modifies the behavioral phase response curve induced by short pulses of bright light. In order to study the influence of the aPVT on SCN neural activity, we addressed whether the stimulation of the aPVT can modulate the electrical response of the SCN to either retinal or RHT stimulation. Using in vitro and in vivo recordings, we found a large population of SCN neurons responsive to the stimulation of either aPVT or RHT pathways. Furthermore, we found that simultaneous stimulation of the aPVT and the RHT increased neuronal responsiveness and spontaneous firing rate (SFR) in neurons with a low basal SFR (which also have more negative membrane potentials), such as quiescent and arrhythmic neurons, but no change was observed in neurons with rhythmic firing patterns and more depolarized membrane potentials. These results suggest that inputs from the aPVT could shift the membrane potential of an SCN neuron to values closer to its firing threshold and thus contribute to integration of the response of the circadian clock to light. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.


Author Keywords
Circadian;  Hypothalamus;  Intralaminar nuclei;  Light entrainment;  Patch-clamp


Document Type: Article
Source: Scopus




Luchauer, B., Shurtleff, T.
Meaningful Components of Exercise and Active Recreation for Spinal Cord Injuries
(2015) OTJR Occupation, Participation and Health, 35 (4), pp. 232-238. 

DOI: 10.1177/1539449215601069


Washington University, School of Medicine in St. Louis, St. Louis, MO, United States


Abstract
This qualitative study used focus groups to identify meaningful components of exercise and active recreation (E/AR) related to consistent participation for those with spinal cord injury (SCI). Transcripts from each focus group were analyzed with classical content analysis, grounded theory coding, and meaning condensation using the International Classification of Function, Disability and Health (ICF). Variables within each of the ICF domains (body structures and functions, activities/participation, and environment) were indicated as meaningful components leading to increased participation, independence, and reasons why people consistently participated in E/AR. Occupational therapists can utilize these components to implement therapeutic intervisions, which provide clients with a sense of purpose and being, thus improving outcomes in meaningful occupations. © The Author(s) 2015.


Author Keywords
Disability and Health;  International Classification of Function;  physical activity;  qualitative


Document Type: Article
Source: Scopus




Hines, L.A.a , Morley, K.I.a , Strang, J.a , Agrawal, A.b , Nelson, E.C.b , Statham, D.c , Martin, N.G.d , Lynskey, M.T.a
Onset of opportunity to use cannabis and progression from opportunity to dependence: Are influences consistent across transitions?
(2016) Drug and Alcohol Dependence, . Article in Press. 

DOI: 10.1016/j.drugalcdep.2015.12.032


a Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England, UK
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
c School of Social Sciences, University of the Sunshine Coast, Queensland, Australia
d QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia


Abstract
Background: There is a developing body of research looking at cannabis use opportunity, but little research examining timing of opportunity to use cannabis. Aims: Identify factors associated with (1) earlier opportunity to use cannabis and (2) faster progression from opportunity to cannabis dependence. Method: Cross-sectional study of 3824 Australian twins and siblings, measuring age of onset of cannabis use opportunity and DSM-IV cannabis dependence. Survival analysis identified factors associated with faster progression to opportunity or dependence. Results: Factors associated with both speed of progression to opportunity and dependence were conduct disorder (opportunity HR 5.57, 95%CI 1.52-20.47; dependence HR 2.49, 95%CI 1.91-3.25), parental drug problems (opportunity HR 7.29, 95%CI 1.74-30.62; dependence HR 3.30, 95%CI 1.63-6.69), weekly tobacco use (opportunity HR 8.57, 95%CI 3.93-18.68; dependence HR 2.76, 95% CI 2.10-3.64), and female gender (opportunity HR 0.69, 95%CI 0.64-0.75; dependence HR 0.44, 95%CI 0.34-0.55). Frequent childhood religious attendance (HR 0.74, 95%CI 0.68-0.80), parental conflict (HR 1.09, 95%CI 1.00-1.18), parental alcohol problems (HR 1.19, 95%CI 1.08-1.30) and childhood sexual abuse (HR 1.17, 95%CI 1.01-1.34) were uniquely associated with transition to opportunity. Depressive episode (HR 1.44, 95%CI 1.12-1.85), tobacco dependence (HR 1.36, 95%CI 1.04-1.78), alcohol dependence (HR 2.64, 95%CI 1.53-4.58), other drug use (HR 2.10, 95%CI 1.64-2.69) and other drug dependence (HR 2.75, 95%CI 1.70-4.43) were uniquely associated with progression to dependence. Conclusion: The profile of factors associated with opportunity to use cannabis and dependence only partially overlaps, suggesting targeting of interventions may benefit from being tailored to the stages of drug use. © 2016 Elsevier Ireland Ltd.


Author Keywords
Cannabis;  Dependence;  Etiology;  Opportunity;  Risk factors;  Substance use;  Survival analysis;  Transitions


Document Type: Article in Press
Source: Scopus




Sun, M.a , Hu, X.b , Zhang, W.a , Guo, R.a , Hu, A.a , Mwansisya, T.E.c , Zhou, L.a , Liu, C.a , Chen, X.a , Huang, X.a , Shi, J.d , Chiu, H.F.K.e , Liu, Z.a
Psychotic-like experiences and associated socio-demographic factors among adolescents in China
(2015) Schizophrenia Research, 166 (1-3), pp. 49-54. 

DOI: 10.1016/j.schres.2015.05.031


a Institute of Mental Health, The Second Xiangya Hospital of Central South University, Changsha, China
b School of Medicine and Institute for Public Health, Washington University, St. Louis, United States
c College of Health Sciences, University of Dodoma, P.O. Box 395, Dodoma, Tanzania
d School of Public Health, Central South University, Changsha, China
e Department of Psychiatry, Chinese University of Hong Kong, Hong Kong


Abstract
Objective: Adolescents with persistent psychotic-like experiences (PLEs) may be at high risk for later development of psychoses. Exploring early age risk factors for PLEs may provide useful information for prevention of mental disorders and improvement of mental health. Method: A total of 5427 adolescents (aged between 10 and 16) participated in a cross-sectional survey, with social and demographic information collected. The Positive Subscale of Community Assessment of Psychic Experiences (CAPE) was used to measure PLEs, and the CAPE Depressive and Negative Subscales were used to examine depressive and negative experiences. The Trauma History Questionnaire (child version) was used to assess experiences of previous traumatic events. Results: In our study, 95.7% of the adolescents reported more than one episode of PLEs, while 17.2% reported "nearly always" having PLEs. High positive correlations were shown both between frequency scores among experiences of three dimensions (PLEs, depressive and negative experiences), and between frequency and distress scores. Factors associated with a higher risk for more frequent and distressing PLEs include: urban setting, family history of psychiatric illnesses, and higher impact from previous traumatic events at present. Conclusions: Episodes of PLEs are common in Chinese adolescents, however only a small proportion have persistent PLEs, with worsening distress as the frequency increased. PLEs shared similar environmental and genetic risk factors not only with the clinical phenotypes, which is consistent with the continuity model of PLEs, but also with depressive and negative experiences, which may imply etiologic relation between different dimensions of psychosis at the subclinical level. © 2015 Elsevier B.V.


Author Keywords
CAPE;  Left-behind children;  Psychosis;  Trauma history


Document Type: Article
Source: Scopus




Bilbao, J.M., Schmidt, R.E.
Biopsy diagnosis of peripheral neuropathy, second edition
(2015) Biopsy Diagnosis of Peripheral Neuropathy, Second Edition, pp. 1-486. 

DOI: 10.1007/978-3-319-07311-8


Division of Neuropathology, Department of Pathology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Peripheral nerve analysis is a challenging task for pathologists, given the advent of new diagnoses and techniques of analysis and the impact of molecular genetics. This book presents a simple, logical method for constructing a differential diagnosis based on pathology and clinical presentation. It also provides advice on the selection of ancillary molecular, immunohistochemical and genetic techniques to establish a definitive diagnosis. Clear, authoritative guidance is offered on diagnosis of the full range of neuropathies with the aid of a wealth of high-quality color photomicrographs and electron micrographs. The pathologist will benefit greatly from the identification of a variety of artifacts and normal structures occasionally encountered in nerve biopsies that need to be distinguished from specific pathologic alterations. This user-friendly, practical text will be an invaluable aid in achieving the most specific diagnosis possible. © Springer International Publishing Switzerland 2015.

 


Document Type: Book
Source: Scopus