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Office of Neuroscience Research > Resources and Facilities > WUSTL Neuroscience Publications for the week > Weekly Neuroscience Publications - Archives > Neuroscience Publications Archive - July 2017

Neuroscience Publications Archive - July 2017

Scopus Weekly Report

July 31, 2017

July 24, 2017

July 10, 2017

July 3, 2017

 

July 31, 2017

1) 

Cuneo, M.G., Schrepf, A., Slavich, G.M., Thaker, P.H., Goodheart, M., Bender, D., Cole, S.W., Sood, A.K., Lutgendorf, S.K.
Diurnal cortisol rhythms, fatigue and psychosocial factors in five-year survivors of ovarian cancer
(2017) Psychoneuroendocrinology, 84, pp. 139-142. 

DOI: 10.1016/j.psyneuen.2017.06.019


a Department of Psychological & Brain Sciences, University of Iowa, W322 Seashore Hall, Iowa City, IA, United States
b Chronic Pain and Fatigue Research Center and Department of Anesthesiology, University of Michigan, 24 Frank Lloyd Wright Dr., Ann Arbor, MI, United States
c Cousins Center for Psychoneuroimmunology and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, UCLA Medical Plaza 300, Room 3156, Los Angeles, CA, United States
d Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO, United States
e Holden Comprehensive Cancer Center, University of Iowa; Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Iowa, 200 Hawkins Drive, Iowa City, IA, United States
f Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Iowa, 200 Hawkins Drive, Iowa City, IA, United States
g Department of Medicine Division of Hematology/Oncology and Molecular Biology Institute, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, United States
h Departments of Gynecologic Oncology, Cancer Biology and Center for RNA Interference and Noncoding RNA, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States
i Holden Comprehensive Cancer Center, University of Iowa, Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Iowa, United States and Department of Urology, University of Iowa, University of Iowa, W322 Seashore Hall, Iowa City, IA, United States


Abstract
Fatigue is a challenge in ovarian cancer survivorship and greatly impacts quality of life. In other cancer populations, fatigue has been associated with abnormal diurnal cortisol patterns. However, little is known about biological and behavioral factors in 5+-year ovarian cancer survivors and potential mechanisms underlying persistent fatigue have not been investigated in this population. Moreover, relationships between neuroendocrine and psychosocial factors in 5+-year ovarian cancer survivors have not been studied. We addressed these issues by examining relationships between diurnal cortisol rhythms, fatigue, life stress, and social support in 30 survivors of ovarian cancer who were assessed at least 5 years (mean = 6.20 years) following their primary diagnosis. Flatter diurnal cortisol slopes were associated with higher levels of fatigue, suggesting a role for HPA-axis dysregulation in sustained fatigue experienced by survivors. Moreover, greater cumulative lifetime stressor exposure (p = 0.023) and stressor severity (p = 0.004) were associated with flatter diurnal cortisol slopes, while higher social attachment (p = 0.001) was associated with steeper diurnal cortisol slopes. These findings suggest that ovarian cancer survivors with greater lifetime stress exposure or lower social attachment may be at increased risk for circadian rhythm disruption, which in turn is associated with fatigue. Future research should examine relationships of clinical stage and inflammatory cytokines to cortisol rhythms and fatigue in long-term ovarian cancer survivors, as well as investigating the clinical significance of abnormal diurnal cortisol profiles in this population. © 2017 Elsevier Ltd


Author Keywords
Cortisol;  Fatigue;  Life stress;  Long-term survival;  Ovarian cancer;  Social support


Document Type: Article
Source: Scopus

 

2) 

Collier, T.J., Srivastava, K.R., Justman, C., Grammatopoulous, T., Hutter-Paier, B., Prokesch, M., Havas, D., Rochet, J.-C., Liu, F., Jock, K., de Oliveira, P., Stirtz, G.L., Dettmer, U., Sortwell, C.E., Feany, M.B., Lansbury, P., Lapidus, L., Paumier, K.L.
Nortriptyline inhibits aggregation and neurotoxicity of alpha-synuclein by enhancing reconfiguration of the monomeric form
(2017) Neurobiology of Disease, 106, pp. 191-204. 

DOI: 10.1016/j.nbd.2017.07.007


a Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, United States
c Mercy Health Hauenstein Neuroscience Center, Grand Rapids, MI, United States
d Department of Physics and Astronomy, Michigan State University, East Lansing, MI, United States
e Lysosomal Therapeutics, Inc., Cambridge, MA, United States
f BioEnergetics, Boston, MA, United States
g QPS Research, Graz, Austria
h Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, United States
j Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
k Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States
l Department of Neurology, Washington University, Saint Louis, MO, United States


Abstract
The pathology of Parkinson's disease and other synucleinopathies is characterized by the formation of intracellular inclusions comprised primarily of misfolded, fibrillar α-synuclein (α-syn). One strategy to slow disease progression is to prevent the misfolding and aggregation of its native monomeric form. Here we present findings that support the contention that the tricyclic antidepressant compound nortriptyline (NOR) has disease-modifying potential for synucleinopathies. Findings from in vitro aggregation and kinetics assays support the view that NOR inhibits aggregation of α-syn by directly binding to the soluble, monomeric form, and by enhancing reconfiguration of the monomer, inhibits formation of toxic conformations of the protein. We go on to demonstrate that NOR inhibits the accumulation, aggregation and neurotoxicity of α-syn in multiple cell and animal models. These findings suggest that NOR, a compound with established safety and efficacy for treatment of depression, may slow progression of α-syn pathology by directly binding to soluble, native, α-syn, thereby inhibiting pathological aggregation and preserving its normal functions. © 2017 Elsevier Inc.


Author Keywords
Alpha-synuclein;  Antidepressants;  Biophysics;  Nortriptyline;  Parkinson's disease;  Pre-formed fibrils;  Transgenic Drosophila;  Transgenic mouse


Document Type: Article
Source: Scopus

 

3) 

Reilly, P., Winston, C.N., Baron, K.R., Trejo, M., Rockenstein, E.M., Akers, J.C., Kfoury, N., Diamond, M., Masliah, E., Rissman, R.A., Yuan, S.H.
Novel human neuronal tau model exhibiting neurofibrillary tangles and transcellular propagation
(2017) Neurobiology of Disease, 106, pp. 222-234. 

DOI: 10.1016/j.nbd.2017.06.005


a Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, United States
b Department of Pathology, University of California San Diego, School of Medicine, La Jolla, CA, United States
c Department of Neurosurgery, University of California San Diego, School of Medicine, La Jolla, CA, United States
d Department of Neurology, Washington University, Saint Louis, MO, United States
e Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
f Department of Pediatrics, Washington University, Saint Louis, MO, United States
g Department of Neurology and Neurotherapeutics, University of Texas, Southwestern, Dallas, TX, United States
h National Institute on Aging, Bethesda, MD, United States


Abstract
Tauopathies are a class of neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy, which are associated with the pathological aggregation of tau protein into neurofibrillary tangles (NFT). Studies have characterized tau as a “prion-like” protein given its ability to form distinct, stable amyloid conformations capable of transcellular and multigenerational propagation in clonal fashion. It has been proposed that progression of tauopathy could be due to the prion-like propagation of tau, suggesting the possibility that end-stage pathologies, like NFT formation, may require an instigating event such as tau seeding. To investigate this, we applied a novel human induced pluripotent stem cell (hiPSC) system we have developed to serve as a human neuronal model. We introduced the tau repeat domain (tau-RD) with P301L and V337M (tau-RD-LM) mutations into hiPSC-derived neurons and observed expression of tau-RD at levels similar to total tau in postmortem AD brains. Tau aggregation occurred without the addition of recombinant tau fibrils. The conditioned media from tau-RD cultures contained tau-RD seeds, which were capable of inducing aggregate formation in homotypic mode in non-transduced recipient neuronal cultures. The resultant NFTs were thioflavin-positive, silver stain-positive, and assumed fibrillary appearance on transmission electron microscopy (TEM) with immunogold, which revealed paired helical filament 1 (PHF1)-positive NFTs, representing possible recruitment of endogenous tau in the aggregates. Functionally, expression of tau-RD caused neurotoxicity that manifested as axon retraction, synaptic density reduction, and enlargement of lysosomes. The results of our hiPSC study were reinforced by the observation that Tau-RD-LM is excreted in exosomes, which mediated the transfer of human tau to wild-type mouse neurons in vivo. Our hiPSC human neuronal system provides a model for further studies of tau aggregation and pathology as well as a means to study transcellular propagation and related neurodegenerative mechanisms. © 2017 Elsevier Inc.


Author Keywords
Exosomes;  Induced pluripotent stem cells;  Neurofibrillary tangles;  Propagation;  Tau


Document Type: Article
Source: Scopus

 

4) 

Ryckman, J., Hilton, C., Rogers, C., Pineda, R.
Sensory processing disorder in preterm infants during early childhood and relationships to early neurobehavior
(2017) Early Human Development, 113, pp. 18-22. 

DOI: 10.1016/j.earlhumdev.2017.07.012


a Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
b Department of Occupational Therapy, School of Health Professions, University of Texas Medical Branch, Galveston, TX, United States
c Department of Pediatrics, Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Background Preterm infants are exposed to a variety of sensory stimuli that they are not developmentally prepared to handle, which puts them at risk for developing a sensory processing disorder. However, the patterns and predictors of sensory processing disorder and their relationship to early behavior at term equivalent age are poorly understood. Objectives The aims of the study are to: 1) describe the incidence of sensory processing disorder in preterm infants at four to six years of age, 2) define medical and sociodemographic factors that relate to sensory processing disorder, and 3) explore relationships between early neurobehavior at term equivalent age and sensory processing disorder at age four to six years. Methods This study was a prospective longitudinal design. Thirty-two preterm infants born ≤ 30 weeks gestation were enrolled. Infants had standardized neurobehavioral testing at term equivalent age with the NICU Network Neurobehavioral Scale. At four to six years of age, participants were assessed with the Sensory Processing Assessment for Young Children (SPA). Results Sixteen children (50%) had at least one abnormal score on the SPA, indicating a sensory processing disorder. There were no identified relationships between medical and sociodemographic factors and sensory processing disorder. More sub-optimal reflexes (p = 0.04) and more signs of stress (p = 0.02) at term equivalent age were related to having a sensory processing disorder in early childhood. Conclusion Preterm infants are at an increased risk for developing a sensory processing disorder. Medical and sociodemographic factors related to sensory processing disorder could not be isolated in this study, however relationships between sensory processing disorder and early neurobehavior were identified. © 2017 Elsevier B.V.


Author Keywords
Neurobehavior;  NICU;  Prematurity;  Sensory processing disorder


Document Type: Article
Source: Scopus

 

5) 

Newland, P., Kimutis, A., Salter, A., Flick, L., Thomas, F.P., Rantz, M., Skubic, M.
Continuous In-Home Symptom and Mobility Measures for Individuals with Multiple Sclerosis: A Case Presentation
(2017) Journal of Neuroscience Nursing, 49 (4), pp. 241-246. 

DOI: 10.1097/JNN.0000000000000299


a Goldfarb School of Nursing, Barnes Jewish College, St Louis, MO, United States
b Staff Nurse, St Louis Children Hospital, St Louis, MO, United States
c Division of Biostatistics, Washington University School of Medicine, St Louis, MO, United States
d Emerita of Epidemiology and Nursing, St Louis University, St Louis, MO., United States
e Multiple Sclerosis Center, Hackensack University Medical Center, Seton Hall University, South Orange, NJ, United States
f Sinclair School of Nursing, University of Missouri, Columbia, MO, United States
g Electrical and Computer Engineering Department, University of Missouri, Columbia, MO, United States


Abstract
Gait impairment represents one of the most common and disabling symptoms of multiple sclerosis (MS). To identify which temporal or spatial parameters of gait could be used as outcome measures in interventional studies of individuals with MS with different levels of disability, we evaluated characteristics of these parameters in a case study of 3 participants with MS, using 1 case as an exemplar and the other participants as validation. A case study of an exemplar participant was conducted with a 67-year-old woman with secondary progressive MS served as exemplar, with 2 other participants (52 and 55 years old) as validation. The primary outcome measures we used were stride time, stride length, gait velocity, and daily symptoms. Stride length and velocity of gait decreased with increasing pain and fatigue. The step time was significantly longer later in the day, whereas the step length remained the same. Stride length and velocity are associated with the level of fatigue and pain, as well as the time of day. These characteristics and parameters of gait need to be considered in future studies of gait in MS, with particular attention to temporality of occurrence in persons with MS. © 2017 American Association of Neuroscience Nurses.


Author Keywords
case study;  gait;  multiple sclerosis;  step length;  stride time;  stride velocity;  symptoms


Document Type: Article
Source: Scopus

 

6) 

Campian, J., Gutmann, D.H.
CNS tumors in neurofibromatosis
(2017) Journal of Clinical Oncology, 35 (21), pp. 2378-2385. Cited 1 time.

DOI: 10.1200/JCO.2016.71.7199


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


Abstract
Neurofibromatosis (NF) encompasses a group of distinct genetic disorders in which affected children and adults are prone to the development of benign and malignant tumors of the nervous system. The purpose of this review is to discuss the spectrum of CNS tumors arising in individuals with NF type 1 (NF1) and NF type 2 (NF2), their pathogenic etiologies, and the rational treatment options for people with these neoplasms. This article is a review of preclinical and clinical data focused on the treatment of the most common CNS tumors encountered in children and adults with NF1 and NF2. Although children with NF1 are at risk for developing low-grade gliomas of the optic pathway and brainstem, individuals with NF2 typically manifest low-grade tumors affecting the cranial nerves (vestibular schwannomas), meninges (meningiomas), and spinal cord (ependymomas). With the identification of the NF1 and NF2 genes, molecularly targeted therapies are beginning to emerge, as a result of a deeper understanding of the mechanisms underlying NF1 and NF2 protein function. As we enter into an era of precision oncology, a more comprehensive awareness of the factors that increase the risk of developing CNS cancers in affected individuals, coupled with a greater appreciation of the cellular and molecular determinants that maintain tumor growth, will undoubtedly yield more effective therapies for these cancer predisposition syndromes. © 2017 by American Society of Clinical Oncology.


Document Type: Review
Source: Scopus



7) 

Shyng, C., Nelvagal, H.R., Dearborn, J.T., Tyynelä, J., Schmidt, R.E., Sands, M.S., Cooper, J.D.
Synergistic effects of treating the spinal cord and brain in CLN1 disease
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (29), pp. E5920-E5929. 

DOI: 10.1073/pnas.1701832114


a Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
c Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, University of California, Los Angeles, Torrance, CA, United States
d Institute of Biomedicine/Biochemistry, University of Helsinki, Helsinki, Finland
e Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
g Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, United States


Abstract
Infantile neuronal ceroid lipofuscinosis (INCL, or CLN1 disease) is an inherited neurodegenerative storage disorder caused by a deficiency of the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1). It was widely believed that the pathology associated with INCL was limited to the brain, but we have now found unexpectedly profound pathology in the human INCL spinal cord. Similar pathological changes also occur at every level of the spinal cord of PPT1-deficient (Ppt1−/−) mice before the onset of neuropathology in the brain. Various forebrain-directed gene therapy approaches have only had limited success in Ppt1−/− mice. Targeting the spinal cord via intrathecal administration of an adeno-associated virus (AAV) gene transfer vector significantly prevented pathology and produced significant improvements in life span and motor function in Ppt1−/− mice. Surprisingly, forebrain-directed gene therapy resulted in essentially no PPT1 activity in the spinal cord, and vice versa. This leads to a reciprocal pattern of histological correction in the respective tissues when comparing intracranial with intrathecal injections. However, the characteristic pathological features of INCL were almost completely absent in both the brain and spinal cord when intracranial and intrathecal injections of the same AAV vector were combined. Targeting both the brain and spinal cord also produced dramatic and synergistic improvements in motor function with an unprecedented increase in life span. These data show that spinal cord pathology significantly contributes to the clinical progression of INCL and can be effectively targeted therapeutically. This has important implications for the delivery of therapies in INCL, and potentially in other similar disorders. © 2017, National Academy of Sciences. All rights reserved.


Author Keywords
Adeno-associated virus;  Brain;  Combination therapy;  Infantile Batten disease;  Spinal cord


Document Type: Article
Source: Scopus

 

8) 

Merrill, R.K., Zebala, L.P., Peters, C., Qureshi, S.A., McAnany, S.J.
The Impact of Depression on Patient Reported Outcome Measures After Lumbar Spine Decompression
(2017) Spine, . Article in Press. 

DOI: 10.1097/BRS.0000000000002329


*Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai- New York, NY †Department of Orthopedic Surgery, Washington University School of Medicine – St. Louis, MO ‡Department of Orthopedic Surgery, Hospital For Special Surgery – New York, NY.


Abstract
STUDY DESIGN.: Retrospective cohort study. OBJECTIVE.: To investigate the effect depression has on the improvement of patient reported outcome measures (PROMs) following lumbar decompression. SUMMARY OF BACKGROUND DATA.: Decompression without fusion is a viable treatment option for lumbar spine stenosis. Depression reportedly has a negative impact on PROMs after certain types of spine surgery, though verification of this with new, more precise outcome measures is needed. METHODS.: We included consecutive adult patients who underwent lumbar decompression for lumbar spine stenosis between 2016–2017 who had PROM information system (PROMIS) physical function, pain, depression, and Oswestry Disability Index (ODI) questionnaires completed pre-operatively and at 6 month follow-up. Patients with a PROMIS depression score >50 or <50 were allocated to the depressed and not depressed groups, respectively. The cohorts were compared using unpaired t-tests and repeated measures two-way ANOVA with statistical significance taken at p?<?0.05. RESULTS.: The analysis included 55 patients without depression and 56 patients with depression. Depressed patients had worse pre-operative PROMIS physical function (30.08 vs. 36.66, p?=?0.005) PROMIS pain (69.36 vs. 64.69, p?<?0.0001), and ODI scores (51.92 vs. 36.35, p?<?0.0001). Similarly, the depressed group had worse post-operative PROMIS physical function (36.29 vs. 40.34, p?=?0.005), PROMIS pain (60.16 vs. 54.87, p?<?0.0001), and ODI scores (37.01 vs. 23.44, p?=?0.0003). We observed a statistically significant interaction between depression status and pre to post-operative improvement in outcome for PROMIS physical function (F[1,109]?=?102.5, p?<?0.0001) and depression scores (F[1,109]?=?15.38, p?=?0.0002). No interaction was found for pain and ODI scores. CONCLUSIONS.: Our results suggest that depressed patients experience a greater magnitude of improvement in PROMIS physical function and depression scores than non depressed patients. Despite this, depressed patients have worse post-operative outcomes for PROMIS physical function, depression, pain, and ODI. These findings are important for risk stratifying and treating depressed patients prior to lumbar spine decompression.Level of Evidence: 3 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Document Type: Article in Press
Source: Scopus

 

9) 

McDade, E., Bateman, R.J.
Stop Alzheimer's before it starts
(2017) Nature, 547 (7662), pp. 153-155. 

DOI: 10.1038/547153a


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


Document Type: Note
Source: Scopus

 

10) 

Apte, R.S.
Tyrosine kinase inhibitors in age-related macular degeneration
(2017) JAMA Ophthalmology, 135 (7), pp. 767-768. 

DOI: 10.1001/jamaophthalmol.2017.1600


Departments of Ophthalmology and Visual Sciences, Developmental Biology and Medicine, Washington University School of Medicine, 660 S Euclid Ave, PO Box 8096, St Louis, MO, United States


Document Type: Note
Source: Scopus

 

11) 

Witoelar, A., Jansen, I.E., Wang, Y., Desikan, R.S., Gibbs, J.R., Blauwendraat, C., Thompson, W.K., Hernandez, D.G., Djurovic, S., Schork, A.J., Bettella, F., Ellinghaus, D., Franke, A., Lie, B.A., McEvoy, L.K., Karlsen, T.H., Lesage, S., Morris, H.R., Brice, A., Wood, N.W., Heutink, P., Hardy, J., Singleton, A.B., Dale, A.M., Gasser, T., Andreassen, O.A., Sharma, M., Nalls, M.A., Plagnol, V., Sheerin, U.-M., Saad, M., Simon-Sanchez, J., Schulte, C., Sveinbjornsdottir, S., Arepalli, S., Barker, R., Ben-Shlomo, Y., Berendse, H.W., Berg, D., Bhatia, K., De Bie, R.M.A., Biffi, A., Bloem, B., Bochdanovits, Z., Bonin, M., Bras, J.M., Brockmann, K., Brooks, J., Burn, D.J., Majounie, E., Charlesworth, G., Lungu, C., Chen, H., Chinnery, P.F., Chong, S., Clarke, C.E., Cookson, M.R., Cooper, J.M., Corvol, J.C., Counsell, C., Damier, P., Dartigues, J.-F., Deloukas, P., Deuschl, G., Dexter, D.T., Van Dijk, K.D., Dillman, A., Durif, F., Durr, A., Edkins, S., Evans, J.R., Foltynie, T., Dong, J., Gardner, M., Goate, A., Gray, E., Guerreiro, R., Harris, C., Van Hilten, J.J., Hofman, A., Hollenbeck, A., Holton, J., Hu, M., Huang, X., Wurster, I., Matzler, W., Hudson, G., Hunt, S.E., Huttenlocher, J., Illig, T., Jonsson, P.V., Lambert, J.-C., Langford, C., Lees, A., Lichtner, P., Limousin, P., Lopez, G., Lorenz, D., McNeill, A., Moorby, C., Moore, M., Morrison, K.E., Escott-Price, V., Mudanohwo, E., O'Sullivan, S.S., Pearson, J., Perlmutter, J.S., Petursson, H., Pollak, P., Post, B., Potter, S., Ravina, B., Revesz, T., Riess, O., Rivadeneira, F., Rizzu, P., Ryten, M., Sawcer, S., Schapira, A., Scheffer, H., Shaw, K., Shoulson, I., Shulman, J., Sidransky, E., Smith, C., Spencer, C.C.A., Stefansson, H., Stockton, J.D., Strange, A., Talbot, K., Tanner, C.M., Tashakkori-Ghanbaria, A., Tison, F., Trabzuni, D., Traynor, B.J., Uitterlinden, A.G., Velseboer, D., Vidailhet, M., Walker, R., Van De Warrenburg, B., Wickremaratchi, M., Williams, N., Williams-Gray, C.H., Winder-Rhodes, S., Stefansson, K., Martinez, M., Ferrucci, L., Johnson, R., Longo, D.L., Nalls, M.A., O'Brien, R., Troncoso, J., Van Der Brug, M., Zielke, H.R., Zonderman, A., Hardy, J.A., Weale, M.
Genome-wide pleiotropy between Parkinson disease and autoimmune diseases
(2017) JAMA Neurology, 74 (7), pp. 780-792. 

DOI: 10.1001/jamaneurol.2017.0469


a Norwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
b Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
c Department of Clinical Genetics, Vrije Universiteit (VU) University Medical Center, Amsterdam, Netherlands
d German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
e Multimodal Imaging Laboratory, University of California at San Diego, San Diego, United States
f Department of Radiology and Biomedical Imaging, University of California, San Francisco, United States
g Laboratory of Neurogenetics, National Institute On Aging, National Institutes of Health, Bethesda, MD, United States
h Department of Psychiatry, University of California at San Diego, San Diego, United States
i Department of Psychiatry, University of Copenhagen, Copenhagen, Denmark
j Department of Medical Genetics, University of Oslo, Oslo, Norway
k Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
l Sciences Graduate Program, University of California at San Diego, San Diego, United States
m Department of Neurosciences, University of California at San Diego, San Diego, United States
n Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany
o K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo, Norway
p Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway
q Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
r Division of Gastroenterology, Institute of Medicine, University of Bergen, Bergen, Norway
s Norwegian Primary Sclerosing Cholangitis (PSC) Research Center, Department of Transplantation Medicine, Oslo, Norway
t Sorbonne Universites, Universite Pierre-et-Marie Curie (UPMC) Paris 06, UM1127, Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France
u Institut National de la Sante et de la Recherche Medicale (INSERM), Unite 1127, Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France
v Centre National de la Recherche Scientifique (CNRS) UMR 7225, Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France
w Universite Pierre et Marie Curie-Paris, Centre de Recherche, Institut du Cerveau et de la Moelle Epiniere, Paris, France
x Assistance Publique-Hopitaux de Paris, Hopital de la Salpetriere, Departement de Genetique et Cytogenetique, Paris, France
y Department of Clinical Neuroscience, National Hospital for Neurology and Neurosurgery (NHNN), University College London, London, United Kingdom
z Department of Molecular Neurosciences, Institute of Neurology, University College London, London, United Kingdom
aa Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany
ab Rita Lila Weston Institute, University College London, London, United Kingdom
ac Department of Radiology, University of California at San Diego, San Diego, United States
ad Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Silcherstrasse 5, Tubingen, Germany
ae UCL Genetics Institute, London, United Kingdom
af INSERM U563, CPTP, Toulouse, France
ag INSERM UMR 1043, Paul Sabatier University, Toulouse, France
ah INSERM, UMR-S975, UMR-S679, Paris, France
ai CNRS, Paris, France
aj Department of Neurology, Landspitali University Hospital, Reykjavik, Iceland
ak Department of Neurology, MEHT Broomfield Hospital, Chelmsford, Essex, United Kingdom
al Queen Mary College, University of London, London, United Kingdom
am Department of Neurology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
an School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
ao Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, Netherlands
ap Department of Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom
aq Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
ar Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Boston, United States
as Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States
at Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
au Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, Netherlands
av Department of Medical Genetics, Institute of Human Genetics, University of Tubingen, Tubingen, Germany
aw Newcastle University Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle Upon Tyne, United Kingdom
ax National Institutes of Health Parkinson Clinic, NINDS, National Institutes of Health, Bethesda, MD, United States
ay Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States
az NeurologyM4104, Medical School, Framlington Place, Newcastle Upon Tyne, United Kingdom
ba School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom
bb Department of Neurology, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom
bc Department of Clinical Neurosciences, UCL Institute of Neurology, London, United Kingdom
bd INSERM, UMR-S975, Universite Pierre et Marie Curie-Paris, CNRS, UMR 7225, Paris, France
be INSERM CIC-9503, Hopital Pitie-Salpetriere, Paris, France
bf University of Aberdeen, Division of Applied Health Sciences, Population Health Section, Aberdeen, United Kingdom
bg CHU Nantes, CIC0004, Service de Neurologie, Nantes, France
bh INSERM U897, Universite Victor Segalen, Bordeaux, France
bi Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom
bj Klinik fur Neurologie, Universitatsklinikum Schleswig-Holstein, Campus Kiel, Christian Albrechts University of Kiel, Kiel, Germany
bk Parkinson's Disease Research Group, Faculty of Medicine, Imperial College London, London, United Kingdom
bl Service de Neurologie, Hopital Gabriel Montpied, Clermont-Ferrand, France
bm AP-HP, Pitie-Salpetriere Hospital, Paris, France
bn Cambridge Centre for Brain Repair, Cambridge, United Kingdom
bo Departments of Psychiatry and Neurology, Washington University School of Medicine in St Louis, St Louis, MO, United States
bp Department of Neurology, Leiden University Medical Center, Leiden, Netherlands
bq Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands
br AARP, Washington, DC, United States
bs Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, London, United Kingdom
bt University of Oxford, Department of Clinical Neurology, John Radcliffe Hospital, Oxford, United Kingdom
bu Departments of Neurology, Radiology, Neurosurgery, Pharmacology, Kinesiology, and Bioengineering, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, United States
bv DeCODE Genetics, Reykjavik, Iceland
bw Institute of Epidemiology, Helmholtz Zentrum Munchen, German Research Centre for Environmental Health, Neuherberg, Germany
bx Department of Geriatrics, Landspitali University Hospital, Reykjavik, Iceland
by INSERM U744, Lille, France
bz Institut Pasteur de Lille, Universite de Lille Nord, Lille, France
ca Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Centre for Environmental Health, Neuherberg, Germany
cb Institute of Neurology, Sobell Department, Unit of Functional Neurosurgery, London, United Kingdom
cc Section On Molecular Neurogenetics, Medical Genetics Branch, NHGRI, National Institutes of Health, Bethesda, MD, United States
cd Neurosciences Department, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
ce MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, United Kingdom
cf Neurogenetics Unit, UCL Institute of Neurology, London, United Kingdom
cg Departments of Neurology, Radiology, and Neurobiology, Washington University in St Louis, St Louis, MO, United States
ch Service de Neurologie, CHU de Grenoble, Grenoble, France
ci Translational Neurology, Biogen Idec, Cambridge, MA, United States
cj Departments of Epidemiology and Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands
ck University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, United Kingdom
cl Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
cm Department of Neurology, University of Rochester, Rochester, NY, United States
cn Baylor College of Medicine, Houston, TX, United States
co Department of Pathology, University of Edinburgh, Edinburgh, United Kingdom
cp Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
cq Clinical Research Department, Parkinson's Institute and Clinical Center, Sunnyvale, CA, United States
cr Service de Neurologie, Hopital Haut-Leveque, Pessac, France
cs Department of Neurology, Cardiff University, Cardiff, United Kingdom
ct Department of Psychiatry, Medical Research Council, Wellcome Trust Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, United Kingdom
cu Clinical Research Branch, National Institute On Aging, Baltimore, MD, United States
cv NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, United States
cw Lymphocyte Cell Biology Unit, Laboratory of Immunology, National Institute On Aging, National Institutes of Health, Baltimore, MD, United States
cx Brain Resource Center, Johns Hopkins University, Baltimore, MD, United States
cy ITGR Biomarker Discovery Group, Genentech, South San Francisco, CA, United States
cz Research Resources Branch, National Institute On Aging, National Institutes of Health, Bethesda, MD, United States
da Department of Medical and Molecular Genetics, King's College London, London, United Kingdom


Abstract
IMPORTANCE: Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. OBJECTIVES: To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach. DESIGN, SETTING, AND PARTICIPANTS: Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017. MAIN OUTCOMES AND MEASURES: The primary outcomewas a list of novel loci and their pathways involved in PD and autoimmune diseases. RESULTS: Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK, HLA-DRB5, LRRK2, and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA, LRRK2, MAPT, TRIM10, and SETD1A in PD. Among the novel genes discovered, WNT3, KANSL1, CRHR1, BOLA2, and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes inmethylation or expression levels of adjacent genes. CONCLUSIONS AND RELEVANCE: The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes. The results may have implications for future therapeutic trials involving anti-inflammatory agents. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

12) 

Conway, C.R., George, M.S., Sackeim, H.A.
Defining treatment-resistant depression: Reply
(2017) JAMA Psychiatry, 74 (7), p. 759. 

DOI: 10.1001/jamapsychiatry.2017.0970


a Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO, United States
b Medical University of South Carolina, Charleston, United States
c Ralph H. Johnson VA Medical Center, Charleston, SC, United States
d Columbia University, New York, NY, United States


Document Type: Letter
Source: Scopus

 

13) 

Mac Donald, C.L., Barber, J., Jordan, M., Johnson, A.M., Dikmen, S., Fann, J.R., Temkin, N.
Early clinical predictors of 5-year outcome after concussive blast traumatic brain injury
(2017) JAMA Neurology, 74 (7), pp. 821-829. 

DOI: 10.1001/jamaneurol.2017.0143


a Department of Neurological Surgery, University of Washington, 352 9th Ave, Box 359924, Seattle, WA, United States
b Center for Clinical Studies, Washington University, St Louis, MO, United States
c Department of Rehabilitation Medicine, University of Washington, Seattle, United States
d Department of Psychiatry, University of Washington, Seattle, United States
e Department of Biostatistics, University of Washington, Seattle, United States


Abstract
IMPORTANCE: The long-term clinical effects of wartime traumatic brain injuries (TBIs), most of which are mild, remain incompletely described. Current medical disability cost estimates from world conflicts continually surpass projections. Additional information regarding long-term functional trajectory is needed to reduce this extensive public health burden. OBJECTIVES: To examine 5-year clinical outcomes leveraging existing clinical data collected at 1 year after injury in the same patients and to identify early risk factors for long-term disability. DESIGN, SETTING, AND PARTICIPANTS: This prospective, longitudinal study enrolled active-duty US military after concussive blast injury (n = 50) in the acute to subacute stage and combat-deployed control individuals (n = 44) in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. One- and 5-year clinical evaluations were completed in the United States. All concussive blast injuriesmet the Department of Defense definition of mild, uncomplicated TBI. In-person clinical evaluations included standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden that were essentially identical to the evaluations completed at 1-year follow-up. Data were analyzed from October 1 through November 30, 2016. MAIN OUTCOMES AND MEASURES: Changes in the in-person standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden from the 1- to 5-year follow-up. Predictive modeling was used to identify early risk factors for long-term disability. RESULTS; Among the 94 participants (87 men [93%] and 7 women [7%]; mean [SD] age, 34 [8] years), global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the 5-year evaluation. Logistic regression on the dichotomized Extended Glasgow Outcome Scale (GOS-E) at 5 years as a measure of overall disability identified brain injury diagnosis, preinjury intelligence, motor strength, verbal fluency, and neurobehavioral symptom severity at 1 year as risk factors for a poor outcome at 5 years, with an area under the curve of 0.92 indicating excellent prediction strength. Thirty-six of 50 patients with concussive blast TBI (72%) had a decline in the GOS-E from the 1- to 5-year evaluations, in contrast with only 5 of 44 combat-deployed controls (11%).Worsening of symptoms in concussive blast TBI was also observed on measures of posttraumatic stress disorder and depression. Service members with concussive blast TBI experienced evolution, not resolution, of symptoms from the 1- to 5-year outcomes. CONCLUSIONS AND RELEVANCE: Considerable declinewas observed in military service members with concussive blast TBI when comparing 1- and 5-year clinical outcomes. These results advocate for new treatment strategies to combat the long-term and extremely costly effect of these wartime injuries. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

14) 

Boyd, L.A., Hayward, K.S., Ward, N.S., Stinear, C.M., Rosso, C., Fisher, R.J., Carter, A.R., Leff, A.P., Copland, D.A., Carey, L.M., Cohen, L.G., Basso, D.M., Maguire, J.M., Cramer, S.C.
Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable
(2017) International Journal of Stroke, 12 (5), pp. 480-493. 

DOI: 10.1177/1747493017714176


a Department of Physical Therapy, the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
b Department of Physical Therapy, University of British Columbia, Vancouver, Canada
c Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia
d Sobell Department of Motor Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom
e Department of Medicine and Centre for Brain Research, University of Auckland, Auckland, New Zealand
f Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
g AP-HP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France
h Division of Rehabilitation & Ageing, University of Nottingham, Nottingham, United Kingdom
i Department of Neurology, Washington University in Saint Louis, St Louis, MO, United States
j Department of Brain Repair and Rehabilitation, Institute of Neurology & Institute of Cognitive Neuroscience, University College London, Queens Square, London, United Kingdom
k School of Health & Rehabilitation Sciences, University of Queensland, Brisbane, Australia
l University of Queensland Centre for Clinical Research, Brisbane, Australia
m School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora, Australia
n Neurorehabilitation and Recovery, Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia
o Human Cortical Physiology and Neurorehabilitation Section, NINDS, NIH, Bethesda, MD, United States
p School of Health and Rehabilitation Sciences, The Ohio State University, Columbus, OH, United States
q Faculty of Health, University of Technology, Ultimo, Sydney, Australia
r University of California, Irvine, CA, United States
s Depts. Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, Irvine, CA, United States


Abstract
The most difficult clinical questions in stroke rehabilitation are “What is this patient’s potential for recovery?” and “What is the best rehabilitation strategy for this person, given her/his clinical profile?” Without answers to these questions, clinicians struggle to make decisions regarding the content and focus of therapy, and researchers design studies that inadvertently mix participants who have a high likelihood of responding with those who do not. Developing and implementing biomarkers that distinguish patient subgroups will help address these issues and unravel the factors important to the recovery process. The goal of the present paper is to provide a consensus statement regarding the current state of the evidence for stroke recovery biomarkers. Biomarkers of motor, somatosensory, cognitive and language domains across the recovery timeline post-stroke are considered; with focus on brain structure and function, and exclusion of blood markers and genetics. We provide evidence for biomarkers that are considered ready to be included in clinical trials, as well as others that are promising but not ready and so represent a developmental priority. We conclude with an example that illustrates the utility of biomarkers in recovery and rehabilitation research, demonstrating how the inclusion of a biomarker may enhance future clinical trials. In this way, we propose a way forward for when and where we can include biomarkers to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke. © 2017, © 2017 World Stroke Organization.


Author Keywords
Biomarker;  clinical trial;  cognition;  function;  human;  language;  motor;  neuroimaging;  somatosensory;  stratification


Document Type: Article
Source: Scopus

 

15) 

Cui, V., Tedeschi, C.M., Kronzer, V.L., McKinnon, S.L., Avidan, M.S.
Protocol for an observational study of delirium in the post-anaesthesia care unit (PACU) as a potential predictor of subsequent postoperative delirium
(2017) BMJ Open, 7 (7), art. no. e016402, . 

DOI: 10.1136/bmjopen-2017-016402


Department of Anesthesia, Washington University School of Medicine, Saint Louis, MO, United States


Abstract
Introduction Postoperative delirium can be a serious consequence of major surgery, associated with longer hospital stays, readmission, cognitive and functional deterioration and mortality. Delirium is an acute, reversible disorder characterised by fluctuating course, inattention, disorganised thinking and altered level of consciousness. Delirium occurring in the hours immediately following anaesthesia and delirium occurring in the postoperative period of 1-5 days have been described as distinct clinical entities. This protocol describes an observational study with the aim of determining if delirium in the first hour following tracheal tube removal is a predictor of delirium in the 5 subsequent postoperative days. Improved understanding regarding the development of postoperative delirium would improve patient care and allow more effective implementation of delirium prevention measures. Methods and analysis Patients enrolled to the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomised controlled trial will be eligible for this substudy. A validated delirium assessment method, the 3-min Diagnostic Confusion Assessment Method and the Richmond Agitation and Sedation Scale will be used to assess 100 patients for delirium at 30 min and 60 min following tracheal tube removal. Patients will also be assessed for delirium over postoperative days 1-5 using three validated methods, the Confusion Assessment Method (CAM), CAM for the Intensive Care Unit and structured chart review. Logistic regression analysis will then be performed to test whether immediately postoperative delirium independently predicts subsequent postoperative delirium. Ethics and dissemination This observational substudy of ENGAGES has been approved by the ethics board of Washington University School of Medicine. Enrolment began in June 2016 and will continue until June 2017. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration number NCT02241655. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved.


Author Keywords
adult intensive & critical care;  delirium & cognitive disorders


Document Type: Article
Source: Scopus

 

16) 

Smith, E.E., Lee, J.-M.
Lacunes: Black holes in our understanding of cerebral amyloid angiopathy
(2017) Neurology, 88 (23), pp. 2158-2159. 

DOI: 10.1212/WNL.0000000000004017


a Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of CalgaryAB, Canada
b Departments of Neurology, Radiology, and Biomedical Engineering, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Document Type: Editorial
Source: Scopus

 

17) 

Solga, A.C., Toonen, J.A., Pan, Y., Cimino, P.J., Ma, Y., Castillon, G.A., Gianino, S.M., Ellisman, M.H., Lee, D.Y., Gutmann, D.H.
The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation
(2017) Oncotarget, 8 (29), pp. 47206-47215. 

DOI: 10.18632/oncotarget.17589


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
c National Center for Microscopy and Imaging Research, University of California, San Diego, CA, United States


Abstract
Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2+ cells and that Olig2+ oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2+ OPCs could be tumorinitiating cells for Nf1 optic glioma. Similar to the GFAP-Cre transgenic strain previously employed to generate Nf1 optic gliomas, Olig2+ cells also give rise to astrocytes in the murine optic nerve in vivo. However, in contrast to the GFAP-Cre strain where somatic Nf1 inactivation in embryonic neural progenitor/stem cells (Nf1flox/mut; GFAP-Cre mice) results in optic gliomas by 3 months of age in vivo, mice with Nf1 gene inactivation in Olig2+ OPCs (Nf1flox/mut; Olig2-Cre mice) do not form optic gliomas until 6 months of age. These distinct patterns of glioma latency do not reflect differences in the timing or brain location of somatic Nf1 loss. Instead, they most likely reflect the cell of origin, as somatic Nf1 loss in CD133+ neural progenitor/stem cells during late embryogenesis results in optic gliomas at 3 months of age. Collectively, these data demonstrate that the cell of origin dictates the time to tumorigenesis in murine optic glioma. © Solga et al.


Author Keywords
Astrocytoma;  NF1;  OPC;  Pediatric brain tumor;  Tumorigenesis


Document Type: Article
Source: Scopus

 

18) 

McPherson, C., Inder, T.
Perinatal and neonatal use of sedation and analgesia
(2017) Seminars in Fetal and Neonatal Medicine, . Article in Press. 

DOI: 10.1016/j.siny.2017.07.007


a Department of Pharmacy, St Louis Children's Hospital, Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA
b Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, USA


Abstract
Optimal obstetric and neonatal care requires the provision of adequate analgesia for painful procedures. However, anesthetic and analgesic agents have the potential to adversely impact the developing fetal/neonatal brain. In this setting, clinicians must assess the risks and benefits of pharmacologic anesthesia and analgesia for specific indications in this population. General anesthesia is required for non-obstetric surgery and cesarean section in the absence of neuraxial anesthesia for the health of the mother and fetus. Although experimental data raise concerns, human data are reassuring and future research may focus on neuroprotective adjuncts in the setting of repeated or prolonged anesthetic exposures. Opioid analgesia is standard of care for preterm infants undergoing major procedures including invasive surgery and endotracheal intubation. The use of opioids for agitation resulting from mechanical ventilation is controversial, but prevalent. Randomized and retrospective studies detect short-term toxicity with inconclusive long-term impact, suggesting the need to explore alternative therapies. © 2017 Elsevier Ltd.


Author Keywords
Analgesia;  Anesthesia;  Neurodevelopment;  Newborn;  Pain


Document Type: Article in Press
Source: Scopus

 

19) 

Kedia, N., Almisry, M., Bieschke, J.
Glucose directs amyloid-beta into membrane-active oligomers
(2017) Physical Chemistry Chemical Physics, 19 (27), pp. 18036-18046. 

DOI: 10.1039/c7cp02849k


Department of Biomedical Engineering, Washington University, St. Louis, MO, United States


Abstract
Oligomeric amyloid-β 1-42 (Aβ-42) peptides are considered to be the most toxic species connected to the occurrence of Alzheimer's disease. However, not all aggregation conditions promote oligomer formation in vitro, raising the question whether oligomer formation in vivo also requires a specific suitable cellular environment. We recently found that interaction with neuronal membranes initiates aggregation of Aβ-42 and neuronal uptake. Our data suggest that small molecules in the extracellular space can facilitate the formation of membrane-active Aβ-42 oligomers. We analyzed the early stage of Aβ-42 aggregation in the presence of glucose and sucrose and found that these sugars strongly favor Aβ-42 oligomer formation. We characterized oligomers by dynamic light scattering, atomic force microscopy, immuno-transmission electron microscopy and fluorescence cross correlation spectroscopy. We found that Aβ-42 spontaneously and rapidly forms low molecular weight oligomers in the presence of sugars. Slightly acidic pH (6.7-7) greatly favors oligomer formation when compared to the extracellular physiological pH (7.4). Circular dichroism demonstrated that these Aβ-42 oligomers did not adopt a β-sheet structure. Unstructured oligomeric Aβ-42 interacted with membrane bilayers of giant unilamellar vesicles (GUV) and neuronal model cells, facilitated cellular uptake of Aβ-42, and inhibition of mitochondrial activity. Our data therefore suggest that elevated concentrations of glucose within the range observed in diabetic individuals (10 mM) facilitate the formation of membrane-active Aβ-42 oligomers. © the Owner Societies 2017.


Document Type: Article
Source: Scopus

 

20) 

Naunheim, R., Covassin, T., Jacquin, A., Hanley, D., Michelson, E.
Using a brain electrical activity biomarker could aid in the objective identification of mild Traumatic Brain Injury patients
(2017) American Journal of Emergency Medicine, . Article in Press. 

DOI: 10.1016/j.ajem.2017.07.007


a Washington University Barnes Jewish Medical Center, St. Louis, MO, United States
b Sport Concussion Laboratory, Michigan State University, East Lansing, MI, United States
c BrainScope Company, Inc., Bethesda, MD, United States
d Brain Injury Outcomes - The Johns Hopkins Medical Institutions, Baltimore, MD, United States
e Department of Emergency Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States


Author Keywords
BFI;  Biomarkers;  Brain function;  Brain function index;  Concussion;  EEG;  MTBI


Document Type: Article in Press
Source: Scopus

 

21) 

Ovod, V., Ramsey, K.N., Mawuenyega, K.G., Bollinger, J.G., Hicks, T., Schneider, T., Sullivan, M., Paumier, K., Holtzman, D.M., Morris, J.C., Benzinger, T., Fagan, A.M., Patterson, B.W., Bateman, R.J.
Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis
(2017) Alzheimer's and Dementia, . Article in Press. 

DOI: 10.1016/j.jalz.2017.06.2266


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
b Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
c Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
d Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
e Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA


Abstract
Introduction: Cerebrospinal fluid analysis and other measurements of amyloidosis, such as amyloid-binding positron emission tomography studies, are limited by cost and availability. There is a need for a more practical amyloid β (Aβ) biomarker for central nervous system amyloid deposition. Methods: We adapted our previously reported stable isotope labeling kinetics protocol to analyze the turnover kinetics and concentrations of Aβ38, Aβ40, and Aβ42 in human plasma. Results: Aβ isoforms have a half-life of approximately 3 hours in plasma. Aβ38 demonstrated faster turnover kinetics compared with Aβ40 and Aβ42. Faster fractional turnover of Aβ42 relative to Aβ40 and lower Aβ42 and Aβ42/Aβ40 concentrations in amyloid-positive participants were observed. Discussion: Blood plasma Aβ42 shows similar amyloid-associated alterations as we have previously reported in cerebrospinal fluid, suggesting a blood-brain transportation mechanism of Aβ. The stability and sensitivity of plasma Aβ measurements suggest this may be a useful screening test for central nervous system amyloidosis. © 2017 the Alzheimer's Association.


Author Keywords
Amyloid β;  Aβ42;  Human;  Kinetics;  Plasma;  Turnover


Document Type: Article in Press
Source: Scopus

 

22) 

Penalba, V., Asvat, Y., Deshields, T.L., Vanderlan, J.R., Chol, N.
Rates and predictors of psychotherapy utilization after psychosocial evaluation for stem cell transplant
(2017) Psycho-Oncology, . Article in Press. 

DOI: 10.1002/pon.4473


Siteman Cancer Center, Barnes-Jewish Hospital Washington University School of Medicine Saint Louis, Missouri USA


Abstract
Objective: Although standard of care prior to hematopoietic stem cell transplantation (HSCT) includes a psychosocial evaluation, little is known about the rate and predictors of psychotherapy utilization among patients presenting for pre-HSCT evaluations. This study aimed to examine the proportion of patients undergoing pre-HSCT evaluations who subsequently utilize psychotherapy services and to explore predictive factors, including distress, anxiety, depression, and quality of life (QoL). Methods: Participants were a cross-sectional sample of 351 HSCT candidates at an NCI-designated comprehensive cancer center. Questionnaires assessing distress, anxiety, depression, and QoL were administered using validated instruments. Results: A subset of patients, representing 14% of the sample, utilized psychotherapy services. Relative to patients who did not utilize psychological services, patients who followed-up with psychotherapy reported significantly more depressive and anxious symptoms (P < .001) and endorsed worse QoL on the Functional Assessment of Cancer Therapy-General. (P = .04). Of note, a subset of patients who utilized psychotherapy services reported low levels of distress (67%), depression (13%), or anxiety (13%); on the other hand, a subset of patients reported moderate-to-high levels of distress (25%), depression (71%), or anxiety (60%) but did not utilize services. Conclusions: Results indicate that only a small subset of patients presenting for pre-HSCT psychosocial evaluation subsequently utilized psychotherapy services. Most patients who reported psychosocial concerns and who could potentially benefit from intervention did not use psychotherapy services. Further research is necessary to help clarify barriers to psychotherapy service utilization among HSCT patients and to help improve uptake among high-need patients. © 2017 John Wiley & Sons, Ltd.


Author Keywords
Anxiety;  Cancer;  Depression;  Distress;  Hematopoietic stem cell transplantation;  Oncology;  Psychotherapy utilization


Document Type: Article in Press
Source: Scopus

 

23) 

Harrington, K.D., Lim, Y.Y., Ames, D., Hassenstab, J., Laws, S.M., Martins, R.N., Rainey-Smith, S., Robertson, J., Rowe, C.C., Salvado, O., Doré, V., Villemagne, V.L., Snyder, P.J., Masters, C.L., Maruff, P.
Amyloid β–associated cognitive decline in the absence of clinical disease progression and systemic illness
(2017) Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 8, pp. 156-164. 

DOI: 10.1016/j.dadm.2017.05.006


a The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
b Cooperative Research Centre for Mental Health, Parkville, Victoria, Australia
c CogState Ltd., Melbourne, Victoria, Australia
d Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia
e National Ageing Research Institute, Parkville, Victoria, Australia
f Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
g Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
h Department of Psychological & Brain Sciences, Washington University, St. Louis, MO, United States
i Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia
j School of Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin UniversityWestern Australia, Australia
k Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia
l Department of Molecular Imaging, Austin Health, Melbourne, Victoria, Australia
m Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia
n CSIRO Health and Biosecurity, The Australian eHealth Research Centre, Brisbane, Queensland, Australia
o Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, RI, United States
p Department of Neurology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States


Abstract
Introduction High levels of amyloid β (Aβ) are associated with cognitive decline in cognitively normal (CN) older adults. This study investigated the nature of cognitive decline in healthy individuals who did not progress to mild cognitive impairment or dementia. Method Cognition was measured over 72 months and compared between low (Aβ−) and high (Aβ+) CN older adults (n = 335) who did not progress to mild cognitive impairment or dementia and who remained free of severe or uncontrolled systemic illness. Results Compared to the Aβ− group, the Aβ+ group showed no cognitive impairment at baseline but showed substantial decline in verbal learning, episodic memory, and attention over 72 months. Discussion Moderate cognitive decline, particularly for learning and memory, was associated with Aβ+ in CN older adults in the absence of clinical disease progression and uncontrolled or serious comorbid illness. © 2017 The Authors


Author Keywords
Alzheimer disease;  Amyloid;  Cognitive aging;  Memory;  Normal aging


Document Type: Article
Source: Scopus

 

24) 

Anastasaki, C., Dahiya, S., Gutmann, D.H.
KIR2DL5 mutation and loss underlies sporadic dermal neurofibroma pathogenesis and growth
(2017) Oncotarget, 8 (29), pp. 47574-47585. 

DOI: 10.18632/oncotarget.17736


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


Abstract
Dermal neurofibromas (DNFs) are benign peripheral nerve sheath tumors thought to originate from Schwann cell progenitors. These tumors represent one of the hallmarks of the neurofibromatosis type 1 (NF1) tumor predisposition syndrome, where they can number in the thousands. While NF1-DNFs arise due to mutations in the NF1 gene, the vast majority of DNFs occur sporadically (sp-DNFs), where the genetic etiology is currently unknown. Herein, we employed whole-exome sequencing of sp-DNFs to identify a recurrent mutation in the KIR2DL5 gene, which codes for a protein suppressor of natural killer (NK) cell activity. While the function of KIR2DL5 outside of the immune system is unknown, we identified a KIR2DL5N173D mutation in three of nine sp-DNFs, resulting in loss of KIR2DL5 protein expression. In contrast, two of these subjects had unrelated tumors, which retained KIR2DL5 protein expression. Moreover, loss of KIR2DL5 expression was demonstrated in 15 of 45 independentlyidentified sp-DNFs. Consistent with its potential role as a negative growth regulator important for neurofibroma maintenance, ectopic KIR2DL5N173D expression in normal human Schwann cells resulted in reduced KIR2DL5 expression and increased cell proliferation. Similarly, KIR2DL5 short hairpin RNA knockdown (KD) decreased KIR2DL5 protein levels and increased cell proliferation, as well as correlated with PDGFRβ and downstream RAS/AKT/mTOR hyperactivation. Importantly, inhibition of PDGFRβ or AKT/mTOR activity in KIR2DL5-KD human Schwann cells reduced proliferation to control levels. Collectively, these findings establish KIR2DL5 as a new Schwann cell growth regulator relevant to sp-DNF pathogenesis, which links sporadic and NF1-associated DNFs through RAS pathway hyperactivation. © Anastasaki et al.


Author Keywords
KIR2DL5;  RAS/AKT/mTOR signaling;  Schwann cells;  Sporadic neurofibroma;  Tumor suppressor gene


Document Type: Article
Source: Scopus

 

July 24, 2017 

1) 

Bastiani, M., Cottaar, M., Dikranian, K., Ghosh, A., Zhang, H., Alexander, D.C., Behrens, T.E., Jbabdi, S., Sotiropoulos, S.N.
Improved tractography using asymmetric fibre orientation distributions
(2017) NeuroImage, 158, pp. 205-218. 

DOI: 10.1016/j.neuroimage.2017.06.050


a Wellcome Centre for Integrative Neuroscience (WIN) - Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), University of Oxford, United Kingdom
b Department of Neuroscience, Washington University, St. Louis, MO, United States
c Department of Computer Science & Centre for Medical Image Computing, University College London, United Kingdom
d Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, United Kingdom


Abstract
Diffusion MRI allows us to make inferences on the structural organisation of the brain by mapping water diffusion to white matter microstructure. However, such a mapping is generally ill-defined; for instance, diffusion measurements are antipodally symmetric (diffusion along x and –x are equal), whereas the distribution of fibre orientations within a voxel is generally not symmetric. Therefore, different sub-voxel patterns such as crossing, fanning, or sharp bending, cannot be distinguished by fitting a voxel-wise model to the signal. However, asymmetric fibre patterns can potentially be distinguished once spatial information from neighbouring voxels is taken into account. We propose a neighbourhood-constrained spherical deconvolution approach that is capable of inferring asymmetric fibre orientation distributions (A-fods). Importantly, we further design and implement a tractography algorithm that utilises the estimated A-fods, since the commonly used streamline tractography paradigm cannot directly take advantage of the new information. We assess performance using ultra-high resolution histology data where we can compare true orientation distributions against sub-voxel fibre patterns estimated from down-sampled data. Finally, we explore the benefits of A-fods-based tractography using in vivo data by evaluating agreement of tractography predictions with connectivity estimates made using different in-vivo modalities. The proposed approach can reliably estimate complex fibre patterns such as sharp bending and fanning, which voxel-wise approaches cannot estimate. Moreover, histology-based and in-vivo results show that the new framework allows more accurate tractography and reconstruction of maps quantifying (symmetric and asymmetric) fibre complexity. © 2017 The Authors


Author Keywords
Asymmetry;  Connectome;  Diffusion MRI;  Structural connectivity;  Tractography


Document Type: Article
Source: Scopus

 

2) 

Wallace, A.N., Kayan, Y., Austin, M.J., Delgado Almandoz, J.E., Kamran, M., Cross, D.T., III, Moran, C.J., Osbun, J.W., Kansagra, A.P.
Pipeline embolization of posterior communicating artery aneurysms associated with a fetal origin posterior cerebral artery
(2017) Clinical Neurology and Neurosurgery, 160, pp. 83-87. 

DOI: 10.1016/j.clineuro.2017.06.014


a Division of Neurointerventional Radiology, Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, MN, United States
b Department of Radiology, University of Iowa, Iowa City, IA, United States
c Mallinckrodt Institute of Radiology, Washington University, St Louis, MO, United States
d Mallinckrodt Institute of Radiology, Department of Neurosurgery, Washington University, St Louis, MO, United States
e Department of Neurosurgery, Mallinckrodt Institute of Radiology, Department of Neurology, Washington University, St Louis, MO, United States
f Mallinckrodt Institute of Radiology, Departments of Neurosurgery and Neurology, Washington University, St Louis, MO, United States


Abstract
Background and purpose Flow diversion may have advantages in the treatment of posterior communicating artery (PComA) aneurysms associated with a fetal origin posterior cerebral artery (PCA), which can be challenging to treat with conventional techniques. However, a PComA incorporated into the aneurysm may prevent or delay aneurysm occlusion. Also, coverage of a fetal origin PCA risks infarction of a large vascular territory. The purpose of this study was to examine the safety and effectiveness of using the Pipeline Embolization Device (PED) to treat PComA aneurysms associated with a fetal origin PCA. Patients and methods Retrospective review of PComA aneurysms associated with a fetal origin PCA treated with the PED at two neurovascular centers was performed. Periprocedural complications and clinical and angiographic outcomes were reviewed. Results Seven female patients underwent a total of seven PED procedures to treat seven PcomA aneurysms associated with a fetal origin PCA. The symptomatic complication rate was 14% (1/7) per patient and 13% (1/8) per procedure. Angiographic follow up was obtained for 6 of 7 aneurysms. Follow-up DSA at 5–7 months after treatment demonstrated complete occlusion of 17% (1/6) of aneurysms. One aneurysm was retreated with a second PED and occlusion was demonstrated 36 months after the second treatment, yielding an overall complete occlusion rate of 33% (2/6). Conclusions PED treatment was largely ineffective at treating PComA aneurysms associated with a fetal origin PCA, and should only be considered when conventional treatment options, including microsurgical clipping, are not feasible. © 2017 Elsevier B.V.


Author Keywords
Aneurysm;  Angiography;  Flow diverter;  Hemorrhage;  Pipeline;  Stroke


Document Type: Article
Source: Scopus

 

3) 

Fowler, S.L., Klein, W.M.P., Ball, L., McGuire, J., Colditz, G.A., Waters, E.A.
Using an Internet-Based Breast Cancer Risk Assessment Tool to Improve Social-Cognitive Precursors of Physical Activity
(2017) Medical Decision Making, 37 (6), pp. 657-669. 

DOI: 10.1177/0272989X17699835


a National Cancer Institute, Bethesda, MD, United States
b Washington University in St. Louis, School of Medicine, Campus B.8100, 660 S. Euclid Ave, St. Louis, MO, United States


Abstract
Background. Internet-based cancer risk assessment tools might serve as a strategy for translating epidemiological risk prediction research into public health practice. Understanding how such tools affect key social-cognitive precursors of behavior change is crucial for leveraging their potential into effective interventions. Purpose. To test the effects of a publicly available, Internet-based, breast cancer risk assessment tool on social-cognitive precursors of physical activity. Methods. Women (N = 132) aged 40-78 with no personal cancer history indicated their perceived risk of breast cancer and were randomly assigned to receive personalized (www.yourdiseaserisk.wustl.edu) or nonpersonalized breast cancer risk information. Immediately thereafter, breast cancer risk perceptions and physical activity-related behavioral intentions, self-efficacy, and response efficacy were assessed. Results. Personalized information elicited higher intentions, self-efficacy, and response efficacy than nonpersonalized information, P values < 0.05. Self-efficacy and response efficacy mediated the effect of personalizing information on intentions. Women who received personalized information corrected their inaccurate risk perceptions to some extent, P values < 0.05, but few fully accepted the information. Conclusion. Internet-based risk assessment tools can produce beneficial effects on important social-cognitive precursors of behavior change, but lingering skepticism, possibly due to defensive processing, needs to be addressed before the effects can be maximized. © The Author(s) 2017.


Author Keywords
cancer;  health cognitions;  health communication;  risk perception;  risk prediction


Document Type: Article
Source: Scopus

 

4) 

Oh, S.-H., Choi, Y.-B., Kim, J.-H., Weihl, C.C., Ju, J.-S.
Comparisons of ELISA and Western blot assays for detection of autophagy flux
(2017) Data in Brief, 13, pp. 696-699. 

DOI: 10.1016/j.dib.2017.06.045


a Department of Exercise Science, Research Institute of Sports Science, the University of Suwon, 17 Wauan-gil, Bongdam-eup, Hwaseong-si, Gyeonggi-do, South Korea
b Department of Biotechnology and Bioscience, School of Bioindustry, the University of Suwon, 17 Wauan-gil, Bongdam-eup, Hwaseong-si, Gyeonggi-do, South Korea
c Department of Neurology, Washington University School of Medicine, PO Box 8111, 660 South Euclid Avenue, St Louis, MO, United States


Abstract
We analyzed autophagy/mitophagy flux in vitro (C2C12 myotubes) and in vivo (mouse skeletal muscle) following the treatments of autophagy inducers (starvation, rapamycin) and a mitophagy inducer (carbonyl cyanide m-chlorophenylhydrazone, CCCP) using two immunodetection methods, ELISA and Western blotting, and compared their working range, accuracy, and reliability. The ELISAs showed a broader working range than that of the LC3 Western blots (Table 1). Table 2 showed that data value distribution was tighter and the average standard error from the ELISA was much smaller than those of the Western blot, directly relating to the accuracy of the assay. Test-retest reliability analysis showed good reliability for three individual ELISAs (interclass correlation, ≥ 0.7), but poor reliability for three individual Western blots (interclass correlation, ≤ 0.4) (Table 3). © 2017 The Authors


Author Keywords
Autophagy;  ELISA;  Mitophagy;  Skeletal muscle;  Western blot


Document Type: Article
Source: Scopus

 

5) 

Mac Donald, C.L., Johnson, A.M., Wierzechowski, L., Kassner, E., Stewart, T., Nelson, E.C., Werner, N.J., Adam, O.R., Rivet, D.J., Flaherty, S.F., Oh, J.S., Zonies, D., Fang, R., Brody, D.L.
Outcome Trends after US Military Concussive Traumatic Brain Injury
(2017) Journal of Neurotrauma, 34 (14), pp. 2206-2219. 

DOI: 10.1089/neu.2016.4434


a Washington University, School of Medicine, Department of Neurology, 660 S Euclid Avenue, St. Louis, MO, United States
b Department of Neurological Surgery, University of Washington, 325 9th Avenue, Seattle, WA, United States
c Landstuhl Regional Medical Center, Landstuhl, Germany
d Naval Medical Center Portsmouth, Portsmouth, VA, United States
e Department of Neurology, Berkshire Medical Center, Pittsfield, MA, United States
f Department of Neurosurgery, Virginia Commonwealth University, Richmond, VA, United States
g El Paso, TX, United States
h Trauma, Critical Care, and Acute Care Surgery, Walter Reed National Military Medical Center, Bethesda, MD, United States
i Trauma and Critical Care, Oregon Health and Sciences University, Portland, OR, United States
j US Air Force Center for Sustainment of Trauma and Readiness Skills, R. Adams Cowley Shock Trauma Center, University of Maryland, Baltimore, MD, United States


Abstract
Care for US military personnel with combat-related concussive traumatic brain injury (TBI) has substantially changed in recent years, yet trends in clinical outcomes remain largely unknown. Our prospective longitudinal studies of US military personnel with concussive TBI from 2008-2013 at Landstuhl Regional Medical Center in Germany and twp sites in Afghanistan provided an opportunity to assess for changes in outcomes over time and analyze correlates of overall disability. We enrolled 321 active-duty US military personnel who sustained concussive TBI in theater and 254 military controls. We prospectively assessed clinical outcomes 6-12 months later in 199 with concussive TBI and 148 controls. Global disability, neurobehavioral impairment, depression severity, and post-traumatic stress disorder (PTSD) severity were worse in concussive TBI groups in comparison with controls in all cohorts. Global disability primarily reflected a combination of work-related and nonwork-related disability. There was a modest but statistically significant trend toward less PTSD in later cohorts. Specifically, there was a decrease of 5.9 points of 136 possible on the Clinician Administered PTSD Scale (-4.3%) per year (95% confidence interval, 2.8-9.0 points, p = 0.0037 linear regression, p = 0.03 including covariates in generalized linear model). No other significant trends in outcomes were found. Global disability was more common in those with TBI, those evacuated from theater, and those with more severe depression and PTSD. Disability was not significantly related to neuropsychological performance, age, education, self-reported sleep deprivation, injury mechanism, or date of enrollment. Thus, across multiple cohorts of US military personnel with combat-related concussion, 6-12 month outcomes have improved only modestly and are often poor. Future focus on early depression and PTSD after concussive TBI appears warranted. Adverse outcomes are incompletely explained, however, and additional studies with prospective collection of data on acute injury severity and polytrauma, as well as reduced attrition before follow-up will be required to fully address the root causes of persistent disability after wartime injury. © Copyright 2017, Mary Ann Liebert, Inc.


Author Keywords
blast TBI;  clinical outcomes;  concussive TBI;  PTSD


Document Type: Article
Source: Scopus

 

6) 

Cutler, A.J., Mattingly, G.W.
Beyond the pill: new medication delivery options for ADHD
(2017) CNS Spectrums, pp. 1-12. Article in Press. 

DOI: 10.1017/S1092852916000936


a Chief Medical Officer, Florida Clinical Research Center, Bradenton, Florida
b Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri
c Midwest Research Group, Weldon Spring, Missouri


Abstract
Successful treatment of pediatric disorders has necessitated the development of alternative medication formulations, as children may prefer alternative dosage forms to tablets or capsules. This is especially true for attention-deficit/hyperactivity disorder (ADHD), which is one of the most common chronic pediatric conditions and often involves children with a variety of overlapping physical, psychological, or neurodevelopmental disorders. A special challenge for developing alternative dosage forms for ADHD treatment is the incorporation of a once-daily long-acting formulation. Traditional ADHD medication formulations have been limited, and issues surrounding prescribed dosing regimens—including poor medication adherence, difficulty swallowing, and the lack of dosing titration options—persist in ADHD treatment. In other disease areas, the development of alternative formulations has provided options for patients who have issues with consuming solid dosage forms, particularly children and individuals with developmental disorders. In the light of these new developments, several alternative formulations for ADHD medications are under development or have recently become available. This article reviews the various strategies for developing alternative dosage forms in other disease areas and discusses the application of these strategies in ADHD treatment. Alternative dosage forms may increase medication adherence, compliance, and patient preference and, therefore, improve the overall treatment for ADHD. © Cambridge University Press 2016


Author Keywords
Attention-deficit/hyperactivity disorder;  formulation;  stimulant


Document Type: Article in Press
Source: Scopus

 

7) 

Morse, G.A., York, M.M., Dell, N., Blanco, J., Birchmier, C.
Improving outcomes for homeless people with alcohol disorders: a multi-program community-based approach
(2017) Journal of Mental Health, pp. 1-8. Article in Press. 

DOI: 10.1080/09638237.2017.1340617


a Places for People: Community Alternatives for Hope, Health, and Recovery, St. Louis, MO, USA
b Department of Psychology, Southern Illinois University Carbondale, Carbondale, IL, USA
c Department of Psychology, Washington University, St. Louis, MO, USA


Abstract
Background: Relatively few community-based programs have been found to be helpful for homeless people with alcohol disorders, even though this group represents a high-risk, vulnerable population prone to poor outcomes. Aims: This study sought to implement and evaluate intensive community-based programs for homeless people with alcohol disorders. Method: The project worked closely with a homeless outreach team for referrals, and then provided two different, intensive substance abuse treatment approaches matched to the needs of two subgroups: homeless individuals with alcohol disorders without severe mental illness received community reinforcement approach (CRA) and case management services, while those with alcohol and severe mental illness were assigned to assertive community treatment and integrated dual disorders (ACT/IDDT) services. The study enrolled 322 homeless people with alcohol disorders and outcomes were assessed at six months and program discharge. Results: Participants improved significantly over the first six months in a number of outcome areas, including substance abuse, mental health, housing, employment and health; progress generally remained stable between six months and discharge. Conclusions: Community-based programs that coordinate with mobile outreach teams and then provide CRA and ACT/IDDT appear to be promising approaches for helping individuals with alcohol disorders out of homelessness and into recovery. © 2017 Informa UK Limited, trading as Taylor & Francis Group.


Author Keywords
ACT;  community-based treatments for homeless people;  CRA;  dually diagnosed;  homeless;  homeless people with alcohol disorders;  IDDT


Document Type: Article in Press
Source: Scopus

 

8) 

Cavazos-Rehg, P.A., Krauss, M.J., Sowles, S.J., Murphy, G.M., Bierut, L.J.
Exposure to and Content of Marijuana Product Reviews
(2017) Prevention Science, pp. 1-11. Article in Press. 

DOI: 10.1007/s11121-017-0818-9


Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, Box 8134, St. Louis, MO, United States


Abstract
Many individuals now seek out product reviews in order to make an informed decision prior to making a purchase. In this study, we investigate consumers’ exposure to and content within product reviews about marijuana because of their potential to shape marijuana purchasing decisions. The terms “weed review,” “marijuana review,” and “cannabis review” were searched on YouTube on June 10–11, 2015; the team viewed and coded the content of 83 product review videos about marijuana. In addition, we surveyed young adult (18–34 years old) current (past month) marijuana users (n = 742) from across the USA online to assess exposure to product reviews about marijuana and associations with socio-demographic characteristics and marijuana use behaviors. In our content analysis of videos, we observed that the reviewers tended to consume marijuana during the video and often shared personal, favorable experiences towards the marijuana they ingested (e.g., became as high as possible or experienced positive effects on physical and mental health). Most videos normalized marijuana use and could be easily accessed by underage youth. About one third (34%) of the survey participants viewed/sought a product review about marijuana in the past 30 days. In a multivariable logistic regression model, living in a state where recreational use is legal or using multiple forms of marijuana was associated with increased odds of viewing/seeking marijuana reviews. Prevention messages should counter product reviews about marijuana that tend to normalize and promote marijuana use given that they are more readily viewed by individuals who are increasingly susceptible to marijuana’s potential harms. © 2017 Society for Prevention Research


Author Keywords
Internet advertising;  Social networking;  Substance abuse and addiction


Document Type: Article in Press
Source: Scopus

 

9) 

Dong, S., Li, R.
Traffic identification method based on multiple probabilistic neural network model
(2017) Neural Computing and Applications, pp. 1-15. Article in Press. 

DOI: 10.1007/s00521-017-3081-x


a School of Computer Science and Technology, Huazhong University of Science and Technology, Wuhan, China
b School of Computer Science and Technology, Zhoukou Normal University, Zhoukou, China
c Department of Computer Science and Engineering, Washington University in St.Louis, Saint Louis, MO, United States


Abstract
Traffic identification is currently an important challenge for network management and security. In this paper, we propose a novel application identification method named as MPNN to improve the efficiency and flexibility of application identification. MPNN is based on a structure of multiple neural networks, and it uses an individual neural network module to handle a single application; therefore, it can effectively utilize the characteristics of every application; meanwhile, the minimum Bayes method is used in every neural network module. The MPNN method has the following advantages: it can handle more complex network behavior and extend the identified object from complete TCP flows to all TCP+UDP flows. It can improve the identification accuracy of every application, especially for those applications which containing much less traffic than others. The process of changing identified applications become much easier. Due to adopting parallel processing, it has much lower time and space complexity. The theoretical analysis and experimental results show that MPNN could achieve 95% identification accuracy. © 2017 The Natural Computing Applications Forum


Author Keywords
Application behavior characteristic;  Application identification;  High-speed network;  MPNN;  Network measurement;  Neural network


Document Type: Article in Press
Source: Scopus

 

10) 

Basso, D.M., Lang, C.E.
Consideration of Dose and Timing When Applying Interventions after Stroke and Spinal Cord Injury
(2017) Journal of Neurologic Physical Therapy, 41, pp. S24-S31. 

DOI: 10.1097/NPT.0000000000000165


a School of Health and Rehabilitation Sciences, Ohio State University, Columbus, United States
b Washington University School of Medicine, Campus Box 8502, St Louis, MO, United States


Abstract
Background and Purpose: Nearly 4 decades of investigation into the plasticity of the nervous system suggest that both timing and dose could matter. This article provides a synopsis of our lectures at the IV STEP meeting, which presented a perspective of current data on the issues of timing and dose for adult stroke and spinal cord injury motor rehabilitation. Summary of Key Points: For stroke, the prevailing evidence suggests that greater amounts of therapy do not result in better outcomes for upper extremity interventions, regardless of timing. Whether or not greater amounts of therapy result in better outcomes for lower extremity and mobility interventions needs to be explicitly tested. For spinal cord injury, there is a complex interaction of timing postinjury, task-specificity, and the microenvironment of the spinal cord. Inflammation appears to be a key determinant of whether or not an intervention will be beneficial or maladaptive, and specific retraining of eccentric control during gait may be necessary. Recommendations for Clinical Practice: To move beyond the limitations of our current interventions and to effectively reach nonresponders, greater precision in task-specific interventions that are well-Timed to the cellular environment may hold the key. Neurorehabilitation that ameliorates persistent deficits, attains greater recovery, and reclaims nonresponders will decrease institutionalization, improve quality of life, and prevent multiple secondary complications common after stroke and spinal cord injury.


Author Keywords
dose;  outcomes;  spinal cord injury;  stroke;  task-specific training;  timing


Document Type: Article
Source: Scopus

 

11) 

Gu, Y., Jukkola, P., Wang, Q., Esparza, T., Zhao, Y., Brody, D., Gu, C.
Polarity of varicosity initiation in central neuron mechanosensation
(2017) Journal of Cell Biology, 216 (7), pp. 2179-2199. 

DOI: 10.1083/jcb.201606065


a Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, United States
b Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, United States
c Biomedical Engineering Department, The Ohio State University, Columbus, OH, United States
d Department of Neurology, Washington University, St. Louis, MO, United States


Abstract
Little is known about mechanical regulation of morphological and functional polarity of central neurons. In this study, we report that mechanical stress specifically induces varicosities in the axons but not the dendrites of central neurons by activating TRPV4, a Ca2+/Na+-permeable mechanosensitive channel. This process is unexpectedly rapid and reversible, consistent with the formation of axonal varicosities in vivo induced by mechanical impact in a mouse model of mild traumatic brain injury. In contrast, prolonged stimulation of glutamate receptors induces varicosities in dendrites but not in axons. We further show that axonal varicosities are induced by persistent Ca2+ increase, disassembled microtubules (MTs), and subsequently reversible disruption of axonal transport, and are regulated by stable tubulin-only polypeptide, an MT-associated protein. Finally, axonal varicosity initiation can trigger action potentials to antidromically propagate to the soma in retrograde signaling. Therefore, our study demonstrates a new feature of neuronal polarity: axons and dendrites preferentially respond to physical and chemical stresses, respectively. © 2017 Gu et al.


Document Type: Article
Source: Scopus

 

12) 

Wellons, J.C., Shannon, C.N., Holubkov, R., Riva-Cambrin, J., Kulkarni, A.V., Limbrick, D.D., Whitehead, W., Browd, S., Rozzelle, C., Simon, T.D., Tamber, M.S., Oakes, W.J., Drake, J., Luerssen, T.G., Kestle, J.
Shunting outcomes in posthemorrhagic hydrocephalus: Results of a Hydrocephalus Clinical Research Network prospective cohort study
(2017) Journal of Neurosurgery: Pediatrics, 20 (1), pp. 19-29. 

DOI: 10.3171/2017.1.PEDS16496


a Department of Neurosurgery, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN, United States
b Data Coordinating Center, University of Utah, Salt Lake City, UT, United States
c Division of Neurosurgery, University of CalgaryAB, Canada
d Department of Neurosurgery, University of TorontoON, Canada
e Department of Neurosurgery, Washington University St. Louis, Missouri, United States
f Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
g Department of Neurosurgery, University of Washington Medical Center, Seattle, WA, United States
h Department of Neurosurgery, University of Alabama-Birmingham, Alabama, United States
i Department of Pediatrics, University of Washington Medical Center, Seattle, WA, United States
j Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
k Department of Neurosurgery, University of Utah, Salt Lake City, UT, United States


Abstract
OBJECTIVE Previous Hydrocephalus Clinical Research Network (HCRN) retrospective studies have shown a 15% difference in rates of conversion to permanent shunts with the use of ventriculosubgaleal shunts (VSGSs) versus ventricular reservoirs (VRs) as temporization procedures in the treatment of hydrocephalus due to high-grade intraventricular hemorrhage (IVH) of prematurity. Further research in the same study line revealed a strong influence of center-specific decision-making on shunt outcomes. The primary goal of this prospective study was to standardize decision-making across centers to determine true procedural superiority, if any, of VSGS versus VR as a temporization procedure in highgrade IVH of prematurity. METHODS The HCRN conducted a prospective cohort study across 6 centers with an approximate 1.5-to 3-year accrual period (depending on center) followed by 6 months of follow-up. Infants with premature birth, who weighed less than 1500 g, had Grade 3 or 4 IVH of prematurity, and had more than 72 hours of life expectancy were included in the study. Based on a priori consensus, decisions were standardized regarding the timing of initial surgical treatment, upfront shunt versus temporization procedure (VR or VSGS), and when to convert a VR or VSGS to a permanent shunt. Physical examination assessment and surgical technique were also standardized. The primary outcome was the proportion of infants who underwent conversion to a permanent shunt. The major secondary outcomes of interest included infection and other complication rates. RESULTS One hundred forty-five premature infants were enrolled and met criteria for analysis. Using the standardized decision rubrics, 28 infants never reached the threshold for treatment, 11 initially received permanent shunts, 4 were initially treated with endoscopic third ventriculostomy (ETV), and 102 underwent a temporization procedure (36 with VSGSs and 66 with VRs). The 2 temporization cohorts were similar in terms of sex, race, IVH grade, head (orbitofrontal) circumference, and ventricular size at temporization. There were statistically significant differences noted between groups in gestational age, birth weight, and bilaterality of clot burden that were controlled for in post hoc analysis. By Kaplan-Meier analysis, the 180-day rates of conversion to permanent shunts were 63.5% for VSGS and 74.0% for VR (p = 0.36, log-rank test). The infection rate for VSGS was 14% (5/36) and for VR was 17% (11/66; p = 0.71). The overall compliance rate with the standardized decision rubrics was noted to be 90% for all surgeons. CONCLUSIONS A standardized protocol was instituted across all centers of the HCRN. Compliance was high. Choice of temporization techniques in premature infants with IVH does not appear to influence rates of conversion to permanent ventricular CSF diversion. Once management decisions and surgical techniques are standardized across HCRN sites, thus minimizing center effect, the observed difference in conversion rates between VSGSs and VRs is mitigated.


Author Keywords
Hydrocephalus;  Hydrocephalus Clinical Research Network;  Intraventricular hemorrhage;  Prematurity;  Ventricular reservoir;  Ventricular shunt;  Ventriculosubgaleal shunt


Document Type: Article
Source: Scopus

 

13) 

Ganpule, S., Daphalapurkar, N.P., Ramesh, K.T., Knutsen, A.K., Pham, D.L., Bayly, P.V., Prince, J.L.
A Three-Dimensional Computational Human Head Model That Captures Live Human Brain Dynamics
(2017) Journal of Neurotrauma, 34 (13), pp. 2154-2166. 

DOI: 10.1089/neu.2016.4744


a Hopkins Extreme Materials Institute, Johns Hopkins University, Baltimore, MD, United States
b Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States
c Department of Mechanical Engineering, Washington University in St. Louis, St. Louis, MO, United States
d Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, United States


Abstract
Diffuse axonal injury (DAI) is a debilitating consequence of traumatic brain injury (TBI) attributed to abnormal stretching of axons caused by blunt head trauma or acceleration of the head. We developed an anatomically accurate, subject-specific, three-dimensional (3D) computational model of the human brain, and used it to study the dynamic deformations in the substructures of the brain when the head is subjected to rotational accelerations. The computational head models use anatomy and morphology of the white matter fibers obtained using MRI. Subject-specific full-field shearing motions in live human brains obtained through a recently developed tagged MRI imaging technique are then used to validate the models by comparing the measured and predicted heterogeneous dynamic mechanical response of the brain. These results are used to elucidate the dynamics of local shearing deformations in the brain substructures caused by rotational acceleration of the head. Our work demonstrates that the rotational dynamics of the brain has a timescale of 100 ms as determined by the shearing wave speeds, and thus the injuries associated with rotational accelerations likely occur over these time scales. After subject-specific validation using the live human subject data, a representative subject-specific head model is used to simulate a real life scenario that resulted in a concussive injury. Results suggest that regions of the brain, in the form of a toroid, encompassing the white matter, the cortical gray matter, and outer parts of the limbic system have a higher susceptibility to injury under axial rotations of the head. Copyright © 2017, Mary Ann Liebert, Inc.


Author Keywords
computational head model;  DAI;  human brain deformation


Document Type: Article
Source: Scopus

 

14) 

Kelly, M.P., Lenke, L.G., Godzik, J., Pellise, F., Shaffrey, C.I., Smith, J.S., Lewis, S.J., Ames, C.P., Carreon, L.Y., Fehlings, M.G., Schwab, F., Shimer, A.L.
Retrospective analysis underestimates neurological deficits in complex spinal deformity surgery: A Scoli-RISK-1 Study
(2017) Journal of Neurosurgery: Spine, 27 (1), pp. 68-73. 

DOI: 10.3171/2016.12.SPINE161068


a Department of Orthopedic Surgery, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO, United States
b Department of Orthopedic Surgery, Columbia College of Physicians and Surg., New York, NY, United States
c Department of Neurological Surgery, Barrow Neurological Institute, Phoenix, AZ, United States
d Orthopedic Surgery and Traumatology, Universitat Autonoma de Barcelona, Barcelona, Spain
e Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, VA, United States
f Division of Orthopaedics, University of TorontoON, Canada
g Department of Neurological Surgery, University of California, San Francisco, CA, United States
h Norton Leatherman Spine Center, Louisville, KT, United States
i Department of Neurological Surgery, University of Toronto, Ontario, Canada
j Department of Orthopedic Surgery, Hospital for Special Surgery, New York, NY, United States
k Department of Orthopedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, United States


Abstract
OBJECTIVE The authors conducted a study to compare neurological deficit rates associated with complex adult spinal deformity (ASD) surgery when recorded in retrospective and prospective studies. Retrospective studies may underreport neurological deficits due to selection, detection, and recall biases. Prospective studies are expensive and more difficult to perform, but they likely provide more accurate estimates of new neurological deficit rates. METHODS New neurological deficits were recorded in a prospective study of complex ASD surgeries (pSR1) with a defined outcomes measure (decrement in American Spinal Injury Association lower-extremity motor score) for neurological deficits. Using identical inclusion criteria and a subset of participating surgeons, a retrospective study was created (rSR1) and neurological deficit rates were collected. Continuous variables were compared with the Student t-test, with correction for multiple comparisons. Neurological deficit rates were compared using the Mantel-Haenszel method for standardized risks. Statistical significance for the primary outcome measure was p < 0.05. RESULTS Overall, 272 patients were enrolled in pSR1 and 207 patients were enrolled in rSR1. Inclusion criteria, defining complex spinal deformities, and exclusion criteria were identical. Sagittal Cobb measurements were higher in pSR1, although sagittal alignment was similar. Preoperative neurological deficit rates were similar in the groups. Three-column osteotomies were more common in pSR1, particularly vertebral column resection. New neurological deficits were more common in pSR1 (pSR1 17.3% [95% CI 12.6-22.2] and rSR1 9.0% [95% CI 5.0-13.0]; p = 0.01). The majority of deficits in both studies were at the nerve root level, and the distribution of level of injury was similar. CONCLUSIONS New neurological deficit rates were nearly twice as high in the prospective study than the retrospective study with identical inclusion criteria. These findings validate concerns regarding retrospective cohort studies and confirm the need for and value of carefully designed prospective, observational cohort studies in ASD.


Author Keywords
Adult deformity;  Complication;  Neurological deficit


Document Type: Article
Source: Scopus

 

15) 

Becske, T., Potts, M.B., Shapiro, M., Kallmes, D.F., Brinjikji, W., Saatci, I., McDougall, C.G., Szikora, I., Lanzino, G., Moran, C.J., Woo, H.H., Lopes, D.K., Berez, A.L., Cher, D.J., Siddiqui, A.H., Levy, E.I., Albuquerque, F.C., Fiorella, D.J., Berentei, Z., Marosföi, M., Cekirge, S.H., Nelson, P.K.
Pipeline for uncoilable or failed aneurysms: 3-year follow-up results
(2017) Journal of Neurosurgery, 127 (1), pp. 81-88. 

DOI: 10.3171/2015.6.JNS15311


a Department of Radiology, Neurointerventional Service, NYU School of Medicine, NYU Langone Medical Center, 660 First Ave., New York, NY, United States
b Department of Neurology, Neurointerventional Service, NYU School of Medicine, NYU Langone Medical Center, New York, NY, United States
c Department of Neurological Surgery, Neurointerventional Service, NYU School of Medicine, NYU Langone Medical Center, New York, NY, United States
d Department of Neurosurgery, Mayo Clinic, Rochester, MN, United States
e Department of Radiology, Bayindir Hospital, Ankara, Turkey
f Department of Neurological Surgery, Barrow Neurological Institute, Phoenix, AZ, United States
g National Institute of Neurosciences, Budapest, Hungary
h Division of Interventional Neuroradiology, Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
i Department of Neurosurgery, Stony Brook Hospital, Stony Brook, NY, United States
j Department of Neurological Surgery, Rush University Medical Center, Chicago, IL, United States
k Alembic, LLC, Mountain View, United States
l Wild Iris Consulting, Palo Alto, CA, United States
m Departments of Neurological Surgery and Radiology, University of Buffalo, Buffalo, NY, United States


Abstract
OBJECTIVE The long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. METHODS The PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data. RESULTS At 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor late-onset hemorrhagic or ischemic cerebrovascular events or neurological deaths were observed in the 6-month through 3-year posttreatment period. Among 103 surviving patients, 85 underwent functional outcome assessment in which modified Rankin Scale scores of 0-1 were demonstrated in 80 subjects. CONCLUSIONS Pipeline embolization is safe and effective in the treatment of complex large and giant aneurysms of the intracranial internal carotid artery. Unlike more traditional endovascular treatments, flow diversion results in progressive vascular remodeling that leads to complete aneurysm obliteration over longer-term follow-up without delayed aneurysm recanalization and/or growth. © AANS, 2017.


Author Keywords
Cerebral aneurysm;  Flow diversion;  Giant;  Pipeline Embolization Device;  Vascular disorders


Document Type: Article
Source: Scopus

 

16) 

Mishra, S., Mamourian, A.
Seasonal subarachnoid hemorrhage: Temperature or daylight?
(2017) Journal of Neurosurgery, 127 (1), p. 231. 

DOI: 10.3171/2016.12.JNS162966


a Washington University Medical School in St. Louis, St. Louis, MO, United States
b Hospital of the University of Pennsylvania, Philadelphia, PA, United States


Document Type: Letter
Source: Scopus

 

17) 

Elfenbein, H.A., MacCann, C.
A closer look at ability emotional intelligence (EI): What are its component parts, and how do they relate to each other?
(2017) Social and Personality Psychology Compass, 11 (7), art. no. e12324, . 

DOI: 10.1111/spc3.12324


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


Abstract
In this review, we focus on two key questions about the nature of emotional intelligence (EI). First, we consider what the different parts of EI might be, suggesting a taxonomy that builds on the well-known hierarchical four-branch model to include six narrow abilities (emotion perception, emotion expression, emotion attention regulation, emotion understanding, emotion regulation of self, and emotion regulation of others). Second, we review evidence for the interrelations between these six narrow abilities. The interrelationships of the EI narrow abilities are a key criterion for viewing EI as a kind of intelligence, rather than a typical way of behaving. Our review concludes that the six narrow abilities comprising EI are all positively interrelated—the component parts of EI converge to form a whole. In addition, the level of interrelationships shows that emotion expression and emotion perception are clearly separate, with weaker evidence for the separation between emotion regulation of self versus emotion regulation of others. Using the older research tradition of emotion recognition (which predates EI), we present a detailed overview of the relationship between emotion perception and other narrow abilities of EI. We conclude that the narrow facets of EI converge with each other, providing one form of evidence to support the validity of EI as a type of intelligence. © 2017 John Wiley & Sons Ltd


Document Type: Article
Source: Scopus

 

18) 

Barch, D.M.
The neural correlates of transdiagnostic dimensions of psychopathology
(2017) American Journal of Psychiatry, 174 (7), pp. 613-615. 

DOI: 10.1176/appi.ajp.2017.17030289


Department of Psychological and Brain Sciences, Washington University in Saint Louis, St. Louis, United States


Document Type: Review
Source: Scopus

 

19) 

Aaronson, S.T., Sears, P., Ruvuna, F., Bunker, M., Conway, C.R., Dougherty, D.D., Reimherr, F.W., Schwartz, T.L., Zajecka, J.M.
A 5-year observational study of patients with treatment-resistant depression treated with vagus nerve stimulation or treatment as usual: Comparison of response, remission, and suicidality
(2017) American Journal of Psychiatry, 174 (7), pp. 640-648. Cited 1 time.

DOI: 10.1176/appi.ajp.2017.16010034


Sheppard Pratt Health System, Baltimore; Cyberonics, Inc., Houston; the Department of Psychiatry, Washington University in St. Louis; the Psychiatric Neuroscience Program, Massachusetts General Hospital, Boston; Psychiatric Behavior Solutions, Salt Lake City; the Department of Psychiatry, State University of New York Upstate Medical University, Syracuse; and the Department of Psychiatry, Rush University Medical Center, Chicago.


Abstract
Objective: The Treatment-Resistant Depression Registry investigated whether adjunctive vagus nerve stimulation (VNS) with treatment as usual in depression has superior long-term outcomes compared with treatment as usual only. Method: This 5-year, prospective, open-label, nonrandomized, observational registry study was conducted at 61 U.S. sites and included 795 patients who were experiencing a major depressive episode (unipolar or bipolar depression) of at least 2 years' duration or had three or more depressive episodes (including the current episode), and who had failed four or more depression treatments (including ECT). Patients with a history of psychosis or rapid-cycling bipolar disorder were excluded. The primary efficacy measure was response rate, defined as a decrease of ≥50% in baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score at any postbaseline visit during the 5-year study. Secondary efficacy measures included remission. Results: Patients had chronic moderate to severe depression at baseline (the mean MADRS score was 29.3 [SD=6.9] for the treatment-as-usual group and 33.1 [SD=7.0] for the adjunctive VNS group). The registry results indicate that the adjunctive VNS group had better clinical outcomes than the treatment-as-usual group, including a significantly higher 5-year cumulative response rate (67.6% compared with 40.9%) and a significantly higher remission rate (cumulative first-time remitters, 43.3% compared with 25.7%). A subanalysis demonstrated that among patients with a history of response to ECT, those in the adjunctive VNS group had a significantly higher 5-year cumulative response rate than those in the treatment-as-usual group (71.3% compared with 56.9%). A similar significant response differential was observed among ECT nonresponders (59.6% compared with 34.1%). Conclusions: This registry represents the longest and largest naturalistic study of efficacy outcomes in treatment-resistant depression, and it provides additional evidence that adjunctive VNS has enhanced antidepressant effects compared with treatment as usual in this severely ill patient population.


Document Type: Article
Source: Scopus

 

20) 

Vila, P.M., Lewis, S., Cunningham, G., Brereton, J., Espinel, A.G., Roberson, D.W., Shah, R.K.
A Novel Patient Safety Event Reporting Tool in Otolaryngology
(2017) Otolaryngology - Head and Neck Surgery (United States), 157 (1), pp. 117-122. Cited 1 time.

DOI: 10.1177/0194599817700363


a Department of Otolaryngology–Head and Neck Surgery, Washington University, School of Medicine in St Louis, St Louis, MO, United States
b Department of Otolaryngology, SUNY Downstate Medical Center, Brooklyn, NY, United States
c American Academy of Otolaryngology—Head and Neck Surgery Foundation, Alexandria, VA, United States
d Division of Pediatric Otolaryngology, Children’s National Health System, George Washington University, Washington, DC, United States
e Department of Otology and Laryngology, Harvard Medical School, Boston, MA, United States


Abstract
Objective: To report the results of a preliminary analysis of a quality improvement initiative aimed to identify potential latent systems defects. Methods: A pilot study of an anonymous, voluntary, event reporting system made available to all members of the American Academy of Otolaryngology—Head and Neck Surgery was performed. The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index was used to classify error types. Descriptive statistics were used to summarize submissions to the database. Results: In the 53 cases reported to the database over 22 months, the majority involved errors that had resulted in harm (n = 34, 64%), followed by errors that occurred and did not result in harm (n = 7, 13%). Errors occurred predominantly in the hospital (n = 23, 44%) and operating room (n = 19, 35%). Most entries were classified as either technical (n = 21, 39%) or related to postoperative care (n = 15, 30%). Discussion: This preliminary descriptive analysis of a novel otolaryngology patient safety event reporting tool shows that this platform brings unique value to the identification of errors and adverse events in our specialty. Most reported events were classified as errors resulting in harm. The most common type of reported event was a technical error, most often resulting in a nerve injury. Implications for Practice: This reporting tool will likely allow for identification and prioritization of improvement opportunities. This example may serve as a guide for other societies to create similar platforms as we strive for a standardized process for event reporting. © 2017, © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2017.


Author Keywords
incident reporting;  PS/QI;  voluntary patient safety event reporting


Document Type: Article
Source: Scopus

 

21) 

Barch, D.M., Gold, J.M., Kring, A.M.
Paradigms for Assessing Hedonic Processing and Motivation in Humans: Relevance to Understanding Negative Symptoms in Psychopathology
(2017) Schizophrenia Bulletin, 43 (4), pp. 701-705. Cited 1 time.

DOI: 10.1093/schbul/sbx063


a Departments of Psychological and Brain Science and Psychiatry, Washington University, One Brookings Drive, St. Louis, MO, United States
b Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States
c Department of Psychology, University of California at Berkeley, Berkeley, CA, United States


Abstract
Clinicians and researchers have long known that one of the debilitating aspects of psychotic disorders is the presence of "negative symptoms," which involve impairments in hedonic and motivational function, and/or alterations in expressive affect. We have a number of excellent clinical tools available for assessing the presence and severity of negative symptoms. However, to better understand the mechanisms that may give rise to negative symptoms, we need tools and methods that can help distinguish among different potential contributing causes, as a means to develop more targeted intervention pathways. Using such paradigms is particularly important if we wish to understand whether the causes are the same or different across disorders that may share surface features of negative symptoms. This approach is in line with the goals of the Research Diagnostic Criteria Initiative, which advocates understanding the nature of core dimensions of brain-behavior relationships transdiagnostically. Here we highlight some of the emerging measures and paradigms that may help us to parse the nature and causes of negative symptoms, illustrating both the research approaches from which they emerge and the types of constructs that they can help elucidate. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.


Author Keywords
amotivation;  anhedonia;  assessment;  negative symptoms;  psychopathology;  schizophrenia


Document Type: Review
Source: Scopus

 

22) 

Roberts, B.W., Hill, P.L., Davis, J.P.
How to Change Conscientiousness: The Sociogenomic Trait Intervention Model
(2017) Personality Disorders: Theory, Research, and Treatment, 8 (3), pp. 199-205. 

DOI: 10.1037/per0000242


a Department of Psychology, University of Illinois, 603 East Daniel Street, Champaign, IL, United States
b Department of Psychology, University of Tübingen, Germany
c Department of Psychology, Washington University, St. Louis, United States
d Department of Social Work, University of Illinois-Urbana-Champaign, United States


Abstract
Conscientiousness, the propensity to be organized, responsible, self-controlled, industrious, and rulefollowing, is related to numerous important outcomes including many forms of psychopathology. Given the increasing awareness of the importance of conscientiousness, it is becoming common to want to understand how to foster it. In this paper we first describe and update a recent model that was put forward as a theoretically informed intervention to change conscientiousness. We then consider recent life span theories focused on conscientiousness that might inform how best to use existing interventions as well as identify potential moderators of the effectiveness of intervention. Finally, we integrate these perspectives into a framework for how to foster conscientiousness that we label the Sociogenomic Trait Intervention Model (STIM). © 2017 American Psychological Association.


Author Keywords
behavioral activation;  conscientiousness;  intervention;  personality traits;  sociogenomic


Document Type: Article
Source: Scopus

 

23) 

Sabharwal, A., Kotov, R., Szekely, A., Leung, H.-C., Barch, D.M., Mohanty, A.
Neural markers of emotional face perception across psychotic disorders and general population
(2017) Journal of Abnormal Psychology, 126 (5), pp. 663-678. 

DOI: 10.1037/abn0000279


a Department of Psychology, Stony Brook University, United States
b Department of Psychiatry, Stony Brook University, United States
c Departments of Psychology, Psychiatry, and Radiology, Washington University in St. Louis, United States


Abstract
There is considerable variation in negative and positive symptoms of psychosis, global functioning, and emotional face perception (EFP), not only in schizophrenia but also in other psychotic disorders and healthy individuals. However, EFP impairment and its association with worse symptoms and global functioning have been examined largely in the domain of schizophrenia. The present study adopted a dimensional approach to examine the association of behavioral and neural measures of EFP with symptoms of psychosis and global functioning across individuals with schizophrenia spectrum (SZ; N = 28) and other psychotic (OP; N = 29) disorders, and never-psychotic participants (NP; N = 21). Behavioral and functional MRI data were recorded as participants matched emotional expressions of faces and geometrical shapes. Lower accuracy and increased activity in early visual regions, hippocampus, and amygdala during emotion versus shape matching were associated with higher negative, but not positive, symptoms and lower global functioning, across all participants. This association remained even after controlling for group-related (SZ, OP, and NP) variance, dysphoria, and antipsychotic medication status, except in amygdala. Furthermore, negative symptoms mediated the relationship between behavioral and brain EFP measures and global functioning. This study provides some of the first evidence supporting the specific relationship of EFP measures with negative symptoms and global functioning across psychotic and never-psychotic samples, and transdiagnostically across different psychotic disorders. Present findings help bridge the gap between basic EFP-related neuroscience research and clinical research in psychosis, and highlight EFP as a potential symptom-specific marker that tracks global functioning. © 2017 American Psychological Association.


Author Keywords
fMRI;  Global functioning;  Negative symptoms;  Schizophrenia;  Transdiagnostic


Document Type: Article
Source: Scopus

 

24) 

Acri, M.C., Bornheimer, L.A., Jessell, L., Heckman Chomancuzuk, A., Adler, J.G., Gopalan, G., McKay, M.M.
The intersection of extreme poverty and familial mental health in the United States
(2017) Social Work in Mental Health, pp. 1-13. Article in Press. 

DOI: 10.1080/15332985.2017.1319893


a McSilver Institute for Poverty, Policy, & Research, New York University, New York, New York, USA
b New York University Medical Center, New York, New York, USA
c Brown School of Social Work, Washington University in St. Louis, St. Louis, Missouri, USA
d Silver School of Social Work, New York University, New York, New York, USA
e College of Arts and Sciences, New York University, New York, New York, USA
f School of Social Work, University of Maryland, Baltimore, Maryland, USA


Abstract
Approximately 22% of children in the United States live in poverty, with high rates of caregiver depression and child disruptive behavior disorders (DBD). The current study aims to explore the relationships between living in extreme poverty and both child and parent mental health. Data are comprised of findings from the first effectiveness study of the 4Rs and 2Ss intervention, in addition to preliminary data from an implementation study currently underway (n = 484). Families with an annual income of less than $9,999 reported significantly greater child DBD scores and prevalence of clinically significant levels of caregiver depressive symptoms compared to income levels over $10,000. Findings support the recommendation for parental mental health to be attended to within the context of child mental health services. © 2017 Taylor & Francis


Author Keywords
4Rs and 2Ss for strengthening families;  caregiver depression;  disruptive behavior disorders;  extreme poverty


Document Type: Article in Press
Source: Scopus

 

25) 

Stanton, K., Cruitt, P., Kent, A., Stasik-O’Brien, S.M., Ellickson-Larew, S., Watson, D.
Measures of Psychopathology Characterized by Dominance: Articulating their Structure and Relations with Personality and Other Psychopathology
(2017) Journal of Psychopathology and Behavioral Assessment, pp. 1-15. Article in Press. 

DOI: 10.1007/s10862-017-9615-9


a Department of Psychology, University of Notre Dame, 118 Haggar Hall, Notre Dame, IN, United States
b Washington University in St. Louis, St. Louis, MO, United States
c St. Louis University, St. Louis, MO, United States
d Knox College, Galesburg, IL, United States


Abstract
Mania, narcissism, antisocial personality disorder/psychopathy, and substance use (including alcohol use) disorders have been linked through the dominance behavioral system, a biologically based system guiding dominant behavior and responses to perceptions of power (Johnson et al. 2012). We examined the structure and correlates of measures of psychopathology linked to dominance in two studies utilizing student (N = 309) and mixed community/outpatient samples (N = 255), the latter of which incorporated multi-method assessment. Results indicated that grandiose narcissism and some mania-relevant measures are defined by overlapping positive emotionality content (e.g., seeking acclaim, feeling fearless) that shows strong relations with traits related to dominance (e.g., assertiveness, immodesty). Antisocial trait measures also were linked to dominance to some degree, although less strongly than indicators of mania and narcissism. Lastly, even though substance use indicators overlap with other measures of psychopathology showing more substantial relations to dominance, these measures were weakly related to dominance-related traits. These results establish an important and novel connection between grandiose narcissism and mania-relevant measures via their assessment of dominance. Furthermore, results indicate that substance use measures do not assess dominant attitudes and behaviors. However, the extent to which antisocial traits are defined by dominance is less clear, especially given that these studies did not incorporate assessment of social boldness, a construct central to some conceptualizations of psychopathy (Patrick et al. 2009). © 2017 Springer Science+Business Media, LLC


Author Keywords
Externalizing;  Factor analysis;  Five-factor model;  Positive emotionality


Document Type: Article in Press
Source: Scopus

 

26) 

Marceau, K., Cinnamon Bidwell, L., Karoly, H.C., Evans, A.S., Todorov, A.A., Palmer, R.H., Heath, A.C., Knopik, V.S.
Within-Family Effects of Smoking during Pregnancy on ADHD: the Importance of Phenotype
(2017) Journal of Abnormal Child Psychology, pp. 1-15. Article in Press. 

DOI: 10.1007/s10802-017-0320-7


a Department of Human Development and Family Studies, Purdue University, 225 Hanley Hall, 1202 W State Street, West Lafayette, IN, United States
b Division of Behavior Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, United States
c Institute of Cognitive Science, University of Colorado, Boulder, CO, United States
d Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, United States
e Memorial Hospital, Pawtucket, RI, United States
f Warren Alpert School of Medicine, Brown University, Providence, RI, United States
g Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
h Department of Psychology, Emory University, 36 Eagle Row, Atlanta, GA, United States
i Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
j Department of Psychiatry and Human Behavior, Brown University, Providence, RI, United States


Abstract
We sought to test within- and between- family associations of smoking during pregnancy (SDP) and attention deficit-hyperactivity disorder (ADHD) symptoms using a structured interview based on the conventional Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) symptoms and the Strengths and Weaknesses of ADHD-Symptoms and Normal-Behavior (SWAN) scale, which is a population based measure that grew out of the notion that an ADHD diagnosis exists on the extreme end of a continuum of normative behaviors and includes both above- and below- average performance on attention and activity. We used a sibling-comparison approach in a sample of 173 families including siblings aged 7–16 years (52% male) drawn from the state of Missouri, USA, wherein mothers smoked during one pregnancy but not the other. There was a within-family effect of smoking during pregnancy on SWAN hyperactivity/impulsivity and SWAN total ADHD behaviors. The associations between SDP and DSM-IV-based ADHD symptom dimensions as well as SWAN inattention were explained by familial confounds. These findings suggest that SDP exerts a potentially causal effect on increased ADHD hyperactive/impulsive behaviors and that this SDP effect is best captured when hyperactivity/impulsivity is assessed more normatively across the population, rather than specifically assessing problematic behaviors via DSM symptoms. Thus, any potentially causal effect of SDP on ADHD symptom dimensions may be restricted to hyperactive/impulsive behaviors rather than inattention, and normative, non-DSM-IV based behavioral measures may provide a more sensitive test of mechanisms of SDP-ADHD symptom associations, particularly in non-clinical samples. © 2017 Springer Science+Business Media New York


Author Keywords
Attention deficit hyperactivity disorder;  DSM-iv;  Family research;  Prenatal exposure;  Smoking


Document Type: Article in Press
Source: Scopus

 

27) 

Johnson, N.X., Marquine, M.J., Flores, I., Umlauf, A., Baum, C.M., Wong, A.W.K., Young, A.C., Manly, J.J., Heinemann, A.W., Magasi, S., Heaton, R.K.
Racial Differences in Neurocognitive Outcomes Post-Stroke: The Impact of Healthcare Variables
(2017) Journal of the International Neuropsychological Society, pp. 1-13. Article in Press. 

DOI: 10.1017/S1355617717000480


a San Diego State University, Department of Psychology, San Diego, California
b University of California, San Diego, Department of Psychiatry, San Diego, California
c Washington University in St. Louis, Program in Occupational Therapy, St. Louis, Missouri
d Columbia University, Department of Neurology, New York, New York
e Northwestern University, Feinberg School of Medicine, Department of Physical Medicine & Rehabilitation and Rehabilitation Institute of Chicago, Chicago, Illinois
f University of Illinois at Chicago, Department of Occupational Therapy, Chicago, Illinois


Abstract
Objectives: The present study examined differences in neurocognitive outcomes among non-Hispanic Black and White stroke survivors using the NIH Toolbox-Cognition Battery (NIHTB-CB), and investigated the roles of healthcare variables in explaining racial differences in neurocognitive outcomes post-stroke. Methods: One-hundred seventy adults (91 Black; 79 White), who participated in a multisite study were included (age: M=56.4; SD=12.6; education: M=13.7; SD=2.5; 50% male; years post-stroke: 1–18; stroke type: 72% ischemic, 28% hemorrhagic). Neurocognitive function was assessed with the NIHTB-CB, using demographically corrected norms. Participants completed measures of socio-demographic characteristics, health literacy, and healthcare use and access. Stroke severity was assessed with the Modified Rankin Scale. Results: An independent samples t test indicated Blacks showed more neurocognitive impairment (NIHTB-CB Fluid Composite T-score: M=37.63; SD=11.67) than Whites (Fluid T-score: M=42.59, SD=11.54; p=.006). This difference remained significant after adjusting for reading level (NIHTB-CB Oral Reading), and when stratified by stroke severity. Blacks also scored lower on health literacy, reported differences in insurance type, and reported decreased confidence in the doctors treating them. Multivariable models adjusting for reading level and injury severity showed that health literacy and insurance type were statistically significant predictors of the Fluid cognitive composite (p<.001 and p=.02, respectively) and significantly mediated racial differences on neurocognitive impairment. Conclusions: We replicated prior work showing that Blacks are at increased risk for poorer neurocognitive outcomes post-stroke than Whites. Health literacy and insurance type might be important modifiable factors influencing these differences. (JINS, 2017, 23, 1–13) Copyright © The International Neuropsychological Society 2017


Author Keywords
African Americans;  Cerebrovascular accident;  Cognition;  Health literacy;  Healthcare disparities;  Insurance coverage


Document Type: Article in Press
Source: Scopus

 

28) 

Leyns, C.E.G., Holtzman, D.M.
Glial contributions to neurodegeneration in tauopathies
(2017) Molecular Neurodegeneration, 12 (1), art. no. 50, . 

DOI: 10.1186/s13024-017-0192-x


Department of Neurology, Washington University, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, 660 S. Euclid Ave, St. Louis, MO, United States


Abstract
Tauopathies are a broad set of neurodegenerative dementias characterized by aggregation of the tau protein into filamentous inclusions that can be found in neurons and glial cells. Activated microglia, astrocytes and elevated levels of proinflammatory molecules are also pathological hallmarks that are found in brain regions affected by tau pathology. There has been abundant research in recent years to understand the role of gliosis and neuroinflammation in neurodegenerative diseases, particularly in Alzheimer's disease (AD) which is the most common form of dementia. AD is a tauopathy characterized by both extracellular amyloid-β plaques in addition to intracellular neurofibrillary tangles and neuropil threads containing aggregated tau protein. Accumulating evidence suggests that neuroinflammation offers a possible mechanistic link between these pathologies. Additionally, there appears to be a role for neuroinflammation in aggravating tau pathology and neurodegeneration in tauopathies featuring tau deposits as the predominant pathological signature. In this review, we survey the literature regarding inflammatory mechanisms that may impact neurodegeneration in AD and related tauopathies. We consider a physical role for microglia in the spread of tau pathology as well as the non-cell autonomous effects of secreted proinflammatory cytokines, specifically interleukin 1 beta, interleukin 6, tumor necrosis factor alpha and complement proteins. These molecules appear to have direct effects on tau pathophysiology and overall neuronal health. They also indirectly impact neuronal homeostasis by altering glial function. We conclude by proposing a complex role for gliosis and neuroinflammation in accelerating the progression of AD and other tauopathies. © 2017 The Author(s).


Author Keywords
Alzheimer's disease;  Astrocyte;  Gliosis;  Microglia;  Neurodegeneration;  Neuroinflammation;  Tau;  Tauopathy


Document Type: Review
Source: Scopus

 

29) 

Blain-Moraes, S., Tarnal, V., Vanini, G., Bel-Behar, T., Janke, E., Picton, P., Golmirzaie, G., Palanca, B.J.A., Avidan, M.S., Kelz, M.B., Mashour, G.A.
Network efficiency and posterior alpha patterns are markers of recovery from general anesthesia: A high-density electroencephalography study in healthy volunteers
(2017) Frontiers in Human Neuroscience, 11, art. no. 328, . 

DOI: 10.3389/fnhum.2017.00328


a School of Physical and Occupational Therapy, Faculty of Medicine, McGill University, Montreal, QC, Canada
b Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI, United States
c Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, United States
d Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
e Department of Anesthesiology, University of Pennsylvania, Philadelphia, PA, United States
f University of Michigan Medical School, Ann Arbor, MI, United States


Abstract
Recent studies have investigated local oscillations, long-range connectivity, and global network patterns to identify neural changes associated with anesthetic-induced unconsciousness. These studies typically employ anesthetic protocols that either just cross the threshold of unconsciousness, or induce deep unconsciousness for a brief period of time—neither of which models general anesthesia for major surgery. To study neural patterns of unconsciousness and recovery in a clinically-relevant context, we used a realistic anesthetic regimen to induce and maintain unconsciousness in eight healthy participants for 3 h. High-density electroencephalogram (EEG) was acquired throughout and for another 3 h after emergence. Seven epochs of 5-min eyes-closed resting states were extracted from the data at baseline as well as 30, 60, 90, 120, 150, and 180-min post-emergence. Additionally, 5-min epochs were extracted during induction, unconsciousness, and immediately prior to recovery of consciousness, for a total of 10 analysis epochs. The EEG data in each epoch were analyzed using source-localized spectral analysis, phase-lag index, and graph theoretical techniques. Posterior alpha power was significantly depressed during unconsciousness, and gradually approached baseline levels over the 3 h recovery period. Phase-lag index did not distinguish between states of consciousness or stages of recovery. Network efficiency was significantly depressed and network clustering coefficient was significantly increased during unconsciousness; these graph theoretical measures returned to baseline during the 3 h recovery period. Posterior alpha power may be a potential biomarker for normal recovery of functional brain networks after general anesthesia. © 2017 Blain-Moraes, Tarnal, Vanini, Bel-Behar, Janke, Picton, Golmirzaie, Palanca, Avidan, Kelz and Mashour.


Author Keywords
Alpha rhythm;  Cognition;  Consciousness;  Electroencephalography;  General anesthesia;  Graph theory


Document Type: Article
Source: Scopus

 

30) 

Ghidinelli, M., Poitelon, Y., Shin, Y.K., Ameroso, D., Williamson, C., Ferri, C., Pellegatta, M., Espino, K., Mogha, A., Monk, K., Podini, P., Taveggia, C., Nave, K.-A., Wrabetz, L., Park, H.T., Feltri, M.L.
Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination
(2017) PLoS Biology, 15 (6), art. no. e2001408, . 

DOI: 10.1371/journal.pbio.2001408


a Hunter James Kelly Research Institute, Department of Biochemistry and Neurology, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States
b Division of Genetics and Cell Biology, San Raffaele Scientific Institute, DIBIT, Milano, Italy
c UniSR, Vita Salute San Raffaele University, Milan, Italy
d Department of Physiology, Peripheral Neuropathy Research Center, Dong-A University Medical School, Busan, South Korea
e Department of Developmental Biology, Washington University, School of Medicine, St. Louis, MO, United States
f Division of Neuroscience and INSPE, San Raffaele Scientific Institute, DIBIT, Milano, Italy
g Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany


Abstract
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination. Lm211 can inhibit Nrg1III by limiting protein kinase A (PKA) activation, which is required to initiate myelination. We provide evidence that excessive PKA activation amplifies promyelinating signals downstream of neuregulin, including direct activation of the neuregulin receptor ErbB2 and its effector Grb2-Associated Binder-1 (Gab1), thereby elevating the expression of the key transcription factors Oct6 and early growth response protein 2 (Egr2). The inhibitory effect of Lm211 is seen only in fibers of small caliber. These data may explain why hereditary neuropathies associated with decreased laminin function are characterized by focally thick and redundant myelin. © 2017 Ghidinelli et al.


Document Type: Article
Source: Scopus

 

31) 

Birenbaum, N.K., Macewan, M.R., Ray, W.Z.
Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury
(2017) Neural Regeneration Research, 12 (6), pp. 906-909. 

DOI: 10.4103/1673-5374.208565


a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury. © 2017, Medknow Publications. All rights reserved.


Author Keywords
Electromyography;  Muscle force;  Nerve regeneration;  Peripheral nerve interface;  Regenerative electrode;  Spinal cord injury;  Spinal cord lateral hemisection


Document Type: Review
Source: Scopus

 

32) 

Ising, C., Gallardo, G., Leyns, C.E.G., Wong, C.H., Jiang, H., Stewart, F., Koscal, L.J., Roh, J., Robinson, G.O., Serrano, J.R., Holtzman, D.M.
AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse model of tauopathy
(2017) Journal of Experimental Medicine, 214 (5), pp. 1227-1238. 

DOI: 10.1084/jem.20162125


Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, United States


Abstract
Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To investigate whether the Fc domain of HJ8.5 is required for the therapeutic effect, we engineered single-chain variable fragments (scFvs) derived from HJ8.5 with variable linker lengths, all specific to human tau. Based on different binding properties, we selected two anti-tau scFvs and tested their efficacy in vivo by adeno-associated virus-mediated gene transfer to the brain of P301S-tg mice. The scFvs significantly reduced levels of hyperphosphorylated, aggregated tau in brain tissue of P301S-tg mice, associated with a decrease in detergent-soluble tau species. Interestingly, these mice showed substantial levels of scFvs in the cerebrospinal fluid without significant effects on total extracellular tau levels. Therefore, our study provides a novel strategy for anti-tau immunotherapeutics that potentially limits a detrimental proinflammatory response. © 2017 Ising et al.


Document Type: Article
Source: Scopus

 

33) 

Gervain, J., Culver, J.P.
Functional Near Infrared Spectroscopy, Part 1
(2017) Neurophotonics, 4 (2), art. no. 021101, . 

DOI: 10.1117/1.NPh.4.2.021101


a UMR 8242 CNRS-Paris Descartes, Laboratoire Psychologie de la Perception, 45 rue des Saints-Pères, Paris, France
b Washington University, School of Medicine, Department of Radiology, Campus Box 8225, 4525 Scott Avenue, St. Louis, MO, United States


Document Type: Editorial
Source: Scopus

 

34) 

Eggebrecht, A.T., Elison, J.T., Feczko, E., Todorov, A., Wolff, J.J., Kandala, S., Adams, C.M., Snyder, A.Z., Lewis, J.D., Estes, A.M., Zwaigenbaum, L., Botteron, K.N., McKinstry, R.C., Constantino, J.N., Evans, A., Hazlett, H.C., Dager, S., Paterson, S.J., Schultz, R.T., Styner, M.A., Gerig, G., Das, S., Kostopoulos, P., Schlaggar, B.L., Petersen, S.E., Piven, J., Pruett, J.R., Jr, IBIS Network
Joint Attention and Brain Functional Connectivity in Infants and Toddlers
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (3), pp. 1709-1720. 

DOI: 10.1093/cercor/bhw403


a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA
b Institute of Child Development, University of Minnesota, Minneapolis, MN 55455, USA
c Department of Behavioral Neuroscience, Oregon Health & Sciences, Portland, OR 97239, USA
d Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA
e Department of Educational Psychology, University of Minnesota, Minneapolis, MN 55455, USA
f McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada
g Department of Speech and Hearing Sciences, University of Washington, Seattle, WA 98195, USA
h Department of Psychiatry, University of Alberta, 1E1 Walter Mackenzie Health Sciences Centre (WMC), Edmonton, AB T6G 2B7, Canada
i Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
j Department of Radiology, University of Washington, Seattle, WA 98195, USA
k The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA
l Department of Psychology, Temple University, Philadelphia, PA 19122, USA
m Tandon School of Engineering, New York University, Brooklyn, NY 11201, USA
n Department of Neurology, Washington University School of Medicine, St Louis, MO 63110,USA


Abstract
Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. © The Author 2017. Published by Oxford University Press.


Author Keywords
development;  enrichment;  fMRI;  initiating joint attention;  network


Document Type: Article
Source: Scopus

 

35) 

Hobson, B.A., Sisó, S., Rowland, D.J., Harvey, D.J., Bruun, D.A., Garbow, J.R., Lein, P.J.
Magnetic resonance imaging reveals progressive brain injury in rats acutely intoxicated with diisopropylfluorophosphate
(2017) Toxicological Sciences, 157 (2), pp. 342-353. 

DOI: 10.1093/toxsci/kfx049


a Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States
b Department of Research, BioMarin Pharmaceuticals Inc, Novato, CA, United States
c Department of Biomedical Engineering, Center for Molecular and Genomic Imaging College of Engineering, University of California-Davis, Davis, CA, United States
d Department of Public Health Sciences School of Medicine, University of California-Davis, Davis, CA, United States
e Biomedical Magnetic Resonance Laboratory, Mallinckrodt Institute of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Acute intoxication with organophosphates (OPs) can trigger seizures that progress to status epilepticus, and survivors often exhibit chronic neuropathology, cognitive impairment, affective disorders, and/or electroencephalographic abnormalities. Understanding how acute injury transitions to persistent neurological sequelae is critical to developing medical countermeasures for mitigating damage following OP-induced seizures. Here, we used in vivo magnetic resonance imaging (MRI) to monitor the spatiotemporal patterns of neuropathology for 1 month after acute intoxication with diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats administered pyridostigmine bromide (0.1 mg/kg, im) 30min prior to successive administration of DFP (4 mg/kg, sc), atropine sulfate (2 mg/kg, im), and 2-pralidoxime (25 mg/kg, im) exhibited moderate-to-severe seizure behavior. T2-weighted and diffusion-weighted MR imaging prior to DFP exposure and at 3, 7, 14, 21, or 28 days postexposure revealed prominent lesions, tissue atrophy, and ventricular enlargement in discrete brain regions. Lesions varied in intensity and/or extent over time, with the overall magnitude of injury strongly influenced by seizure severity. Importantly, lesions detected by MRI correlated spatially and temporally with histological evidence of brain pathology. Analysis of histogram parameters extracted from frequency distributions of regional apparent diffusion coefficient (ADC) values identified the standard deviation and 90th percentile of the ADC as robust metrics for quantifying persistent and progressive neuropathological changes. The interanimal and interregional variations observed in lesion severity and progression, coupled with potential reinjury following spontaneous recurrent seizures, underscore the advantages of using in vivo imaging to longitudinally monitor neuropathology and, ultimately, therapeutic response, following acute OP intoxication. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.


Author Keywords
Diffusion-weighted MRI;  In vivo imaging;  Organophosphate;  T2-weighted MRI


Document Type: Article
Source: Scopus

 

36) 

Treiman, R., Kessler, B., Boland, K., Clocksin, H., Chen, Z.
Statistical Learning and Spelling: Older Prephonological Spellers Produce More Wordlike Spellings Than Younger Prephonological Spellers
(2017) Child Development, . Article in Press. 

DOI: 10.1111/cdev.12893


Washington University in St. Louis


Abstract
The authors analyzed the spellings of 179 U.S. children (age = 3 years, 2 months-5 years, 6 months) who were prephonological spellers, in that they wrote using letters that did not reflect the phonemes in the target items. Supporting the idea that children use their statistical learning skills to learn about the outer form of writing before they begin to spell phonologically, older prephonological spellers showed more knowledge about English letter patterns than did younger prephonological spellers. The written productions of older prephonological spellers were rated by adults as more similar to English words than were the productions of younger prephonological spellers. The older children s spellings were also more wordlike on several objective measures, including length, variability of letters within words, and digram frequency. © 2017 The Society for Research in Child Development, Inc.


Document Type: Article in Press
Source: Scopus

 

37) 

Lupton, M.K., Benyamin, B., Proitsi, P., Nyholt, D.R., Ferreira, M.A., Montgomery, G.W., Heath, A.C., Madden, P.A., Medland, S.E., Gordon, S.D., Lovestone, S., Tsolaki, M., Kloszewska, I., Soininen, H., Mecocci, P., Vellas, B., Powell, J.F., Bush, A.I., Wright, M.J., Martin, N.G., Whitfield, J.B.
No Genetic Overlap between Circulating Iron Levels and Alzheimer's Disease
(2017) Journal of Alzheimer's Disease, 59 (1), pp. 85-99. 

DOI: 10.3233/JAD-170027


a QIMR Berghofer Medical Research Institute, Brisbane, Australia
b Queensland Brain Institute, University of Queensland, Brisbane, Australia
c Institute of Psychiatry Psychology and Neuroscience, Kings College London, United Kingdom
d Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
e Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
f Washington University, School of Medicine, StLouis, MO, United States
g Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom
h Memory and Dementia Centre, 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece
i Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland
j Department of Neurology, University of Eastern Finland, Kuopio University Hospital, Kuopio, Finland
k Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy
l Gerontopole, CHU, UMR INSERM 1027, University of Toulouse, France
m Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia
n Centre for Advanced Imaging, University of Queensland, Brisbane, Australia


Abstract
Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology. © 2017 IOS Press and the authors. All rights reserved.


Author Keywords
Alzheimer's disease;  apolipoproteins E;  dementia;  ferritin;  genetic profile scores;  genome-wide association study;  iron;  population genetics;  transferrin


Document Type: Article
Source: Scopus

 

38) 

Morshedian, A., Toomey, M.B., Pollock, G.E., Frederiksen, R., Enright, J.M., McCormick, S.D., Cornwall, M.C., Fain, G.L., Corbo, J.C.
Cambrian origin of the CYP27C1-mediated vitamin A1-to-A2 switch, a key mechanism of vertebrate sensory plasticity
(2017) Royal Society Open Science, 4 (7), art. no. 170362, . 

DOI: 10.1098/rsos.170362


a Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, United States
b Department of Ophthalmology and Jules Stein Eye Institute, University of California Los Angeles, St Louis, CA, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States
d Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA, United States
e Conte Anadromous Fish Research Laboratory, US Geological Survey, Leetown Science Center, Turners Falls, MA, United States


Abstract
The spectral composition of ambient light varies across both space and time. Many species of jawed vertebrates adapt to this variation by tuning the sensitivity of their photoreceptors via the expression of CYP27C1, an enzyme that converts vitamin A1 into vitamin A2, thereby shifting the ratio of vitamin A1-based rhodopsin to red-shifted vitamin A2-based porphyropsin in the eye. Here, we show that the sea lamprey (Petromyzon marinus), a jawless vertebrate that diverged from jawed vertebrates during the Cambrian period (approx. 500 Ma), dynamically shifts its photoreceptor spectral sensitivity via vitamin A -to-A chromophore exchange as 1 2 it transitions between photically divergent aquatic habitats. We further show that this shift correlates with high-level expression of the lamprey orthologue of CYP27C1, specifically in the retinal pigment epithelium as in jawed vertebrates. Our results suggest that the CYP27C1-mediated vitamin A1 -to-A2 switch is an evolutionarily ancient mechanism of sensory plasticity that appeared not long after the origin of vertebrates. © 2017 The Authors.


Author Keywords
Petromyzon marinus;  Photoreceptor;  Visual ecology


Document Type: Article
Source: Scopus

 

39) 

Sisó, S., Hobson, B.A., Harvey, D.J., Bruun, D.A., Rowland, D.J., Garbow, J.R., Lein, P.J.
Spatiotemporal progression and remission of lesions in the rat brain following acute intoxication with diisopropylfluorophosphate
(2017) Toxicological Sciences, 157 (2), pp. 330-341. 

DOI: 10.1093/toxsci/kfx048


a Translational Biology in the Department of Research, BioMarin Pharmaceuticals Inc, Novato, CA, United States
b Department of Molecular Biosciences School of Veterinary Medicine, University of California-Davis, Davis, CA, United States
c Department of Public Health Sciences School of Medicine, University of California-Davis, Davis, CA, United States
d Department of Biomedical Engineering and the Center for Molecular, Genomic Imaging College of Engineering, University of California-Davis, Davis, CA, United States
e Biomedical Magnetic Resonance Laboratory, Mallinckrodt Institute of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Similar to organophosphate (OP) nerve agents, diisopropylfluorophosphate (DFP) rapidly and irreversibly inhibits acetylcholinesterase, leading to convulsions that can progress to status epilepticus (SE). However, in contrast to the OP nerve agents, the long-termconsequences of DFP-induced SE are not well known. Thus, we characterized the spatiotemporal profile of neuropathology during the first 2months following acute DFP intoxication. Adult,male Sprague Dawley rats administered pyridostigmine bromide (0.1mg/kg, im) 30min prior to successive administration of DFP (4mg/kg, sc), atropine sulfate (2mg/kg, im), and 2-pralidoxime (25mg/kg, im), exhibited moderate-to-severe seizure behavior, yet survived until euthanized at 0.5 to 60 days post exposure. Analyses of brains and hearts stained with hematoxylin-eosin, or of brains immunostained for neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), or ionized binding adaptermolecule 1 (IBA1), revealed progressive neuronal cell death, neuroinflammation, and tissue remodeling across limbic brain regions and the cerebral cortex, with no detectable pathology in the cerebellumor the heart. The lesion type and progression varied according to brain region and time after exposure. Acrossmultiple brain regions, neuronal necrosis peaked after the first week, and neuroinflammation persisted at least 2 months after intoxication. Notably,mineralization was observed at later times in the thalamus, and to amore limited extent, in the hippocampus. Lesion severity was influenced by the initial seizure severity, and spontaneous recurrent seizures were associated withmore severe brain damage. These findings parallel descriptions of neuropathology in preclinicalmodels of acute intoxication with OP nerve agents, and other seizurogenic chemicals, suggesting conservedmechanisms of pathology downstream of chemical-induced SE. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.


Author Keywords
Histopathology;  Neurodegeneration;  Neuroinflammation;  Organophosphate neurotoxicity


Document Type: Article
Source: Scopus

 

40) 

Yue, X., Jin, H., Liu, H., Luo, Z., Zhang, X., Kaneshige, K., Flores, H.P., Perlmutter, J.S., Parsons, S.M., Tu, Z.
Synthesis, resolution, and: In vitro evaluation of three vesicular acetylcholine transporter ligands and evaluation of the lead fluorine-18 radioligand in a nonhuman primate
(2017) Organic and Biomolecular Chemistry, 15 (24), pp. 5197-5209. 

DOI: 10.1039/c7ob00854f


a Department of Radiology, Washington University, School of Medicine, St Louis, MO, United States
b Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, United States
c Department of Neurology, Washington University, School of Medicine, St Louis, MO, United States


Abstract
The vesicular acetylcholine transporter (VAChT) is a reliable biomarker for assessing cholinergic dysfunction associated with dementia. We recently reported three new potent and selective carbon-11 labeled VAChT radiotracers. Herein, we report the resolution with a Chiralcel OD column of three additional fluorine containing VAChT ligands in which a fluoroethoxy or fluoroethylamino moiety was substituted for the methoxy group. An in vitro competitive binding assay showed that (-)-7 had high potency for VAChT (Ki-VAChT = 0.31 ± 0.03 nM) and excellent selectivity for VAChT versus σ receptors (Ki-σ1 = 1870 ± 250 nM, Ki-σ2 = 5480 ± 140 nM). Three different radiolabeling approaches were explored; the radiosynthesis of (-)-[18F]7 was successfully accomplished via a stepwise two-pot, three-step method with moderate yield (11 ± 2%) and high radiochemical purity (&gt;98%). PET imaging studies in a nonhuman primate indicated that (-)-[18F]7 rapidly entered the brain and accumulated in the VAChT-enriched striatum. The uptake of (-)-[18F]7 in the target striatal area peaked at 10 min and displayed improved clearance kinetics compared to the VAChT tracer [18F]VAT, which has been approved by the Food and Drug Administration (FDA) for first-in-man studies. These studies justify further investigation of (-)-[18F]7 and exploration of the structure-activity relationships of these fluoroethoxy and fluoroethylamino analogs. © 2017 The Royal Society of Chemistry.


Document Type: Article
Source: Scopus

 

41) 

Marom, R., Jain, M., Burrage, L.C., Song, I.-W., Graham, B.H., Brown, C.W., Stevens, S.J., Stegmann, A.P., Gunter, A.T., Kaplan, J.D., Gavrilova, R.H., Shinawi, M., Rosenfeld, J.A., Bae, Y., Tran, A.A., Chen, Y., Lu, J.T., Gibbs, R.A., Eng, C., Yang, Y., Rousseau, J., de Vries, B.B., Campeau, P.M., Lee, B.
Heterozygous variants in ACTL6A, encoding a component of the BAF complex, are associated with intellectual disability
(2017) Human Mutation, . Article in Press. 

DOI: 10.1002/humu.23282


a Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas
b Department of Pediatrics/Genetics Division University of Tennessee Health Science Center Memphis Memphis, Tennessee
c Department of Human Genetics Maastricht University Hospital Maastricht The Netherlands
d Department of Pediatrics Division of Medical Genetics University of Mississippi Medical Center Jackson, Mississippi
e Department of Medical Genetics Mayo Clinic Rochester Minnesota
f Department of Neurology Mayo Clinic Rochester Minnesota
g Department of Pediatrics Division of Genetics and Genomic Medicine Washington University School of Medicine St. Louis Missouri
h Helix San Carlos California
i Human Genome Sequencing Center Baylor College of Medicine Houston Texas
j Department of Pediatrics CHU Ste-Justine and University of Montreal Montreal Canada
k Department of Human Genetics and Donders Centre for Neuroscience Radboud University Medical Center Nijmegen The Netherlands


Abstract
Pathogenic variants in genes encoding components of the BRG1-associated factor (BAF) chromatin remodeling complex have been associated with intellectual disability syndromes. We identified heterozygous, novel variants in ACTL6A, a gene encoding a component of the BAF complex, in three subjects with varying degrees of intellectual disability. Two subjects have missense variants affecting highly conserved amino acid residues within the actin-like domain. Missense mutations in the homologous region in yeast actin were previously reported to be dominant lethal and were associated with impaired binding of the human ACTL6A to β-actin and BRG1. A third subject has a splicing variant that creates an in-frame deletion. Our findings suggest that the variants identified in our subjects may have a deleterious effect on the function of the protein by disturbing the integrity of the BAF complex. Thus, ACTL6A gene mutation analysis should be considered in patients with intellectual disability, learning disabilities, or developmental language disorder. © 2017 Wiley Periodicals, Inc.


Author Keywords
ACTL6A;  BAF complex;  Intellectual disability;  Speech delay


Document Type: Article in Press
Source: Scopus

 

42) 

Chandramouleeswaran, S., Edwin, N.C., Rajaleelan, W.
Dealing with requests for pharmacological cognitive enhancement from healthy students
(2016) Indian journal of medical ethics, 1 (3), p. 196. 


a Staff Psychiatrist, St Stephens College, Delhi University, Delhi 110 054, India,. susmit1984@yahoo.co.in
b Department of Medical Oncology, Washington University School of Medicine, St Louis 63110 Missouri, United States,
c Department of Anaesthesia, St Stephens Hospital, Delhi 110 054, India


Abstract
The use of drugs to enhance cognitive function and academic performance is clearly a global phenomenon, with the reported prevalence of stimulant use among medical students ranging from 15-20%. A multi-institution study from the USA reported a 6.9% lifetime prevalence of non-prescription use of cognitive enhancers among college students. A comprehensive systematic review indicates a 16-29% use of non-prescribed stimulants among all students for reasons that include increasing concentration and alertness. While mental health professionals and guidance counsellors anecdotally recall requests for pharmacological cognitive enhancement from otherwise healthy students, the exact magnitude of this problem in the Indian context is not clear.


Document Type: Letter
Source: Scopus

 

43) 

Tse, C.S., Lam, L.C., Balota, D.A., Leung, G.T., Hau, K.T., Chang, J.F.
Validation of selective attention and memory measures as early markers for Alzheimer's disease
(2016) Hong Kong medical journal = Xianggang yi xue za zhi, 22, pp. S37-S39. 


a Department of Educational Psychology, The Chinese University of Hong Kong
b Department of Psychiatry, The Chinese University of Hong Kong
c Department of Psychology and Neurology, Washington University in St. Louis, USA


Document Type: Article
Source: Scopus

 

July 10, 2017 

1) 

McAmis, N.E., Prospero, D.A., Standeven, J., Ray, W.Z., Zohny, Z., Engsberg, J.R.
Development of a method to compare microsurgery techniques across different levels of surgical experience
(2017) Interdisciplinary Neurosurgery: Advanced Techniques and Case Management, 10, pp. 52-56. 

DOI: 10.1016/j.inat.2017.06.003


a Department of Occupational Therapy, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States
b Department of Neurosurgery, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States


Abstract
Object Surgical training is often seen as very timely and cost consuming as it requires multiple interactions with other experienced physicians. Through the use of video motion capture (VMC), novice surgeon's skills will be compared objectively to those of more experienced surgeons. Methods VMC was used to capture the movements of four neurosurgery residents performing five simple tasks: (1) threading the needle through the provided plastic vessel; (2) pulling the needle through the provided plastic vessel; and (3,4,5) tying the suture three times. Results It was concluded that experienced subjects recorded more accurate and precise motions within a shorter amount of time when compared to novice subjects. There was a decrease in time, elapsed path, and thumb tip distance with increasing experience. Conclusions The use of VMC proves to be a successful way to compare the differences between different levels of surgical expertise and we hope that this research will impact training paradigms for future surgical trainees. © 2017


Author Keywords
Human motion;  Medical education;  Motion capture;  Neurology;  Neurosurgery;  Surgical training


Document Type: Article
Source: Scopus

 

2) 

Vélez, A., Kohashi, T., Lu, A., Carlson, B.A.
The cellular and circuit basis for evolutionary change in sensory perception in mormyrid fishes
(2017) Scientific Reports, 7 (1), art. no. 3783, . 

DOI: 10.1038/s41598-017-03951-y


a Department of Biology, Washington University in St. Louis, St. Louis, MO, United States
b Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan


Abstract
Species differences in perception have been linked to divergence in gross neuroanatomical features of sensory pathways. The anatomical and physiological basis of evolutionary change in sensory processing at cellular and circuit levels, however, is poorly understood. Here, we show how specific changes to a sensory microcircuit are associated with the evolution of a novel perceptual ability. In mormyrid fishes, the ability to detect variation in electric communication signals is correlated with an enlargement of the midbrain exterolateral nucleus (EL), and a differentiation into separate anterior (ELa) and posterior (ELp) regions. We show that the same cell types and connectivity are found in both EL and ELa/ELp. The evolution of ELa/ELp, and the concomitant ability to detect signal variation, is associated with a lengthening of incoming hindbrain axons to form delay lines, allowing for fine temporal analysis of signals. The enlargement of this brain region is also likely due to an overall increase in cell numbers, which would allow for processing of a wider range of timing information. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

3) 

Zahn, R., Green, S., Beaumont, H., Burns, A., Moll, J., Caine, D., Gerhard, A., Hoffman, P., Shaw, B., Grafman, J., Lambon Ralph, M.A.
Frontotemporal lobar degeneration and social behaviour: Dissociation between the knowledge of its consequences and its conceptual meaning
(2017) Cortex, 93, pp. 107-118. 

DOI: 10.1016/j.cortex.2017.05.009


a Institute of Psychiatry, Psychology & Neuroscience, Department of Psychological Medicine, King's College London, London, United Kingdom
b Neuroscience and Aphasia Research Unit, Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester, United Kingdom
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester, United Kingdom
e Cognitive and Behavioral Neuroscience Unit, D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil
f National Hospital for Neurology & Neurosurgery, Queen Square, London, United Kingdom
g Department of Nuclear Medicine and Geriatric Medicine, University Hospital Essen, Germany
h Rehabilitation Institute of Chicago, Chicago, IL, United States
i Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, United States


Abstract
Inappropriate social behaviour is an early symptom of frontotemporal lobar degeneration (FTLD) in both behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Knowledge of social behaviour is essential for appropriate social conduct. The superior anterior temporal lobe (ATL) has been identified as one key neural component for the conceptual knowledge of social behaviour, but it is unknown whether this is dissociable from knowledge of the consequences of social behaviour. Here, we used a newly-developed test of knowledge about long-term and short-term consequences of social behaviour to investigate its impairment in patients with FTLD relative to a previously-developed test of social conceptual knowledge. We included 19 healthy elderly control participants and 19 consecutive patients with features of bvFTD or SD and defined dissociations as performance differences between tasks for each patient (Bonferroni-corrected p < .05). Knowledge of long-term consequences was selectively impaired relative to short-term consequences in five patients and the reverse dissociation occurred in one patient. Six patients showed a selective impairment of social concepts relative to long-term consequences with the reverse dissociation occurring in one patient. These results corroborate the hypothesis that knowledge of long-term consequences of social behaviour is dissociable from knowledge of short-term consequences, as well as of social conceptual knowledge. Confirming our hypothesis, we found that patients with more marked grey matter (GM) volume loss in frontopolar relative to right superior ATL regions of interest exhibited poorer knowledge of the long-term consequences of social behaviour relative to the knowledge of its conceptual meaning and vice versa (n = 15). These findings support the hypothesis that frontopolar and ATL regions represent distinct aspects of social knowledge. This suggests that rather than being unable to suppress urges to behave inappropriately, FTLD patients often lose the knowledge of what appropriate social behaviour is and can therefore not be expected to behave accordingly. © 2017


Author Keywords
Brodmann Area 10;  Disinhibition;  Frontal lobe;  Impulsivity;  Social behaviour


Document Type: Article
Source: Scopus

 

4) 

Rodebaugh, T.L., Tonge, N.A., Weisman, J.S., Lim, M.H., Fernandez, K.C., Bogdan, R.
The behavioral economics of social anxiety disorder reveal a robust effect for interpersonal traits
(2017) Behaviour Research and Therapy, 95, pp. 139-147. 

DOI: 10.1016/j.brat.2017.06.003


Department of Psychological and Brain Sciences, Washington University in St. Louis, United States


Abstract
Recent evidence suggests that reduced generosity among individuals with social anxiety disorder (SAD) in behavioral economic tasks may result from constraint in changing behavior according to interpersonal contingencies. That is, people with SAD may be slower to be more generous when the situation warrants. Conversely, more global effects on generosity may be related to interpersonal vindictiveness, a dimension only somewhat related to SAD. A total of 133 participants, 73 with the generalized form of SAD, completed self-report instruments and a behavioral economic task with simulated interpersonal (friend, romantic partner, stranger) interactions. In a separate visit, friends (n = 88) also came to the lab and rated participants on vindictiveness. Interpersonal vindictiveness was associated with reduced initial and overall giving to simulated friends. SAD predicted a lack of increased giving to a simulated friend, and attenuated an increase in giving to simulated known versus unknown players compared to participants without SAD. Friend-reported vindictiveness predicted in the same direction as diagnosis. However, the findings for SAD were less robust than those for vindictiveness. SAD is perhaps weakly related to behavioral constraint in economic tasks that simulate interpersonal interactions, whereas vindictiveness is strongly related to lower overall generosity as well as (via friend report) behavioral constraint. Further study is needed to better characterize the construct of vindictiveness. Our findings dovetail with the suggestion that SAD is related to impairment in the proposed affiliation and attachment system, but further suggest that direct study of that system may be more fruitful than focusing on disorders. © 2017 Elsevier Ltd


Author Keywords
Behavioral economics;  Interpersonal processes;  RDoC;  Social anxiety disorder


Document Type: Article
Source: Scopus

 

5) 

Searles Nielsen, S., Hu, S., Checkoway, H., Negrete, M., Palmández, P., Bordianu, T., Racette, B.A., Simpson, C.D.
Parkinsonism Signs and Symptoms in Agricultural Pesticide Handlers in Washington State
(2017) Journal of Agromedicine, 22 (3), pp. 215-221. 

DOI: 10.1080/1059924X.2017.1317684


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, School of Medicine, University of Washington, Seattle, WA, United States
c Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, United States
d Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, United States
e School of Public Health, University of the Witwatersrand, Parktown, South Africa


Abstract
Objectives: Examine associations between pesticide exposure and signs or symptoms of parkinsonism. Methods: Prior to the 2014 pesticide spray season, the authors examined 38 active pesticide handlers aged 35 to 65 (median: 43.5) who participated in the State of Washington’s cholinesterase monitoring program in the Yakima Valley, where cholinesterase-inhibiting insecticides are applied in fruit orchards. A movement disorder specialist assessed the workers using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor subscore 3 (UPDRS3). Participants also self-reported work and medical histories, including the UPDRS activities of daily living subscore 2 (UPDRS2). The authors explored the relation between these scores and lifetime occupational pesticide exposure while accounting for age. Results: All participants were Hispanic men born in Mexico who had worked in agriculture for 4 to 43 years (median: 21 years, including 11 years applying pesticides, mostly in the United States). Ten participants (26%) reported difficulty with one or more UPDRS2 activities of daily living (maximum = 2), and nine (24%) had a UPDRS3 >0 (maximum = 10). The most common symptom and sign, respectively, were excess saliva (n = 6) and action tremor (n = 5). UPDRS2 and UPDRS3 scores were unrelated to the number of years applying pesticides, but UPDRS3, especially action tremor, was positively associated with living on or by a farm. Conclusions: Symptoms and signs of parkinsonism were absent to mild in this small sample of active workers who apply cholinesterase-inhibiting insecticides in Washington State, USA. Future studies should be larger and examine older, retired workers with greater cumulative exposure to agricultural pesticides at work and home, including other types of agricultural pesticides. © 2017 Taylor & Francis.


Author Keywords
Cholinesterase inhibitors;  occupational health;  parkinsonian disorders;  Parkinson’s disease;  pesticides


Document Type: Article
Source: Scopus

 

6) 

Jonson-Reid, M., Wideman, E.
Trauma and Very Young Children
(2017) Child and Adolescent Psychiatric Clinics of North America, 26 (3), pp. 477-490. 

DOI: 10.1016/j.chc.2017.02.004


George Warren Brown School of Social Work, Washington University, Campus Box 1196, 1 Brookings Drive, St Louis, MO, United States


Abstract
This article examines the intersection of early childhood mental health and trauma. Working definitions, incidence, and prevalence of trauma events for this population are outlined with an emphasis on children younger than age 4 years. Trauma impacts on early childhood development are reviewed, with attention to clinical consequences, protective factors, and resilience. Best practices for assessment, screening tools, and treatment methods are presented based on the current research. Future implications include clinician and researcher partnerships to increase the number of effective screening and intervention tools for addressing trauma in very young children. © 2017 Elsevier Inc.


Author Keywords
Best practices;  Early childhood;  Screening;  Therapeutic interventions;  Trauma


Document Type: Review
Source: Scopus

 

7) 

Cai, W., Zhang, M., Zhang, Y.
Batch mode active learning for regression with expected model change
(2017) IEEE Transactions on Neural Networks and Learning Systems, 28 (7), art. no. 7454745, pp. 1668-1681. 

DOI: 10.1109/TNNLS.2016.2542184


a Cooperative Medianet Innovation Center, Shanghai Jiao Tong University, Shanghai, China
b Washington University in St. Louis, St. Louis, MO, United States


Abstract
While active learning (AL) has been widely studied for classification problems, limited efforts have been done on AL for regression. In this paper, we introduce a new AL framework for regression, expected model change maximization (EMCM), which aims at choosing the unlabeled data instances that result in the maximum change of the current model once labeled. The model change is quantified as the difference between the current model parameters and the updated parameters after the inclusion of the newly selected examples. In light of the stochastic gradient descent learning rule, we approximate the change as the gradient of the loss function with respect to each single candidate instance. Under the EMCM framework, we propose novel AL algorithms for the linear and nonlinear regression models. In addition, by simulating the behavior of the sequential AL policy when applied for $k$ iterations, we further extend the algorithms to batch mode AL to simultaneously choose a set of $k$ most informative instances at each query time. Extensive experimental results on both UCI and StatLib benchmark data sets have demonstrated that the proposed algorithms are highly effective and efficient. © 2012 IEEE.


Author Keywords
Active learning (AL);  batch mode;  expected model change;  linear regression;  nonlinear regression


Document Type: Article
Source: Scopus

 

8) 

Constantino, J.N., Marrus, N.
The Early Origins of Autism
(2017) Child and Adolescent Psychiatric Clinics of North America, 26 (3), pp. 555-570. 

DOI: 10.1016/j.chc.2017.02.008


Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8504, St Louis, MO, United States


Abstract
Autism spectrum disorders (ASDs) are neurodevelopmental disorders whose core features of impaired social communication and atypical repetitive behaviors and/or restrictions in range of interests emerge in toddlerhood and carry significant implications at successive stages of development. The ability to reliably identify most cases of the condition far earlier than the average age of diagnosis presents a novel opportunity for early intervention, but the availability of such an intervention is disparate across US communities, and its impact is imperfectly understood. New research may transform the clinical approach to these conditions in early childhood. © 2017 Elsevier Inc.


Author Keywords
Autism spectrum disorder;  Diagnosis;  Early childhood development;  Genetics


Document Type: Review
Source: Scopus

 

9) 

De Franco, E., Flanagan, S.E., Yagi, T., Abreu, D., Mahadevan, J., Johnson, M.B., Jones, G., Acosta, F., Mulaudzi, M., Lek, N., Oh, V., Petz, O., Caswell, R., Ellard, S., Urano, F., Hattersley, A.T.
Dominant ER stress-inducing WFS1 mutations underlie a genetic syndrome of neonatal/infancy-onset diabetes, congenital sensorineural deafness, and congenital cataracts
(2017) Diabetes, 66 (7), pp. 2044-2053. 

DOI: 10.2337/db16-1296


a Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom
b Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
c Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
d Department of Pediatrics, Centro Médico Nacional 20 de Noviembre ISSSTE, Mexico City, Mexico
e Department of Paediatrics and Child Health, University of Pretoria Medical School, Pretoria, South Africa
f KK Women's and Children's Hospital, Singapore, Singapore
g Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
h Praxis für Kinder-und Jugendmedizin, Diabetologische Schwerpunktpraxis, Coesfeld, Germany


Abstract
Neonatal diabetes is frequently part of a complex syndrome with extrapancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There are still patients with neonatal diabetes who have novel genetic syndromes. We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic etiology of a syndrome characterized by neonatal diabetes, sensorineural deafness, and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded.We identified 5 patients, including the initial case, with three heterozygous missense mutations in WFS1 (4/5 confirmed de novo). They had diabetes diagnosed before 12 months (2 before 6 months) (5/5), sensorineural deafness diagnosed soon after birth (5/5), congenital cataracts (4/5), and hypotonia (4/5). In vitro studies showed that these WFS1 mutations are functionally different from the known recessive Wolfram syndrome-causing mutations, as they tend to aggregate and induce robust endoplasmic reticulum stress. Our results establish specific dominant WFS1 mutations as a cause of a novel syndrome including neonatal/infancy-onset diabetes, congenital cataracts, and sensorineural deafness. This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome. © 2017 by the American Diabetes Association.


Document Type: Article
Source: Scopus

 

10) 

Tandon, M., Pergjika, A.
Attention Deficit Hyperactivity Disorder in Preschool-Age Children
(2017) Child and Adolescent Psychiatric Clinics of North America, 26 (3), pp. 523-538. 

DOI: 10.1016/j.chc.2017.02.007


Division of Child and Adolescent Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8134, St Louis, MO, United States


Abstract
Attention deficit hyperactivity disorder is a neurodevelopmental disorder marked by age-inappropriate deficits in attention or hyperactivity/impulsivity that interfere with functioning or development. It is highly correlated with other disorders, such as oppositional defiant disorder, conduct disorder, and mood symptoms. The etiology is multifactorial, and neuroimaging findings are nonspecific. Although assessment tools exist, there is variability among them, and historically, parent-teacher agreement has not been consistent. Treatment algorithm for attention deficit hyperactivity disorder in preschoolers includes behavioral interventions first followed by psychopharmacologic treatment when behavioral therapies fail. Other nonpharmacologic and nonbehavioral interventions are discussed including the role of exercise and nutrition. © 2017 Elsevier Inc.


Author Keywords
Assessment;  Attention deficit hyperactivity disorder;  Preschool children;  Treatment


Document Type: Review
Source: Scopus

 

11) 

Marrus, N., Hall, L.
Intellectual Disability and Language Disorder
(2017) Child and Adolescent Psychiatric Clinics of North America, 26 (3), pp. 539-554. 

DOI: 10.1016/j.chc.2017.03.001


a Department of Psychiatry, Division of Child and Adolescent Psychiatry, Washington University in St Louis, 660 South Euclid Avenue, Box 8504, St Louis, MO, United States
b Department of Psychology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, United States


Abstract
Intellectual disability (ID) and language disorders are neurodevelopmental conditions arising in early childhood. Child psychiatrists are likely to encounter children with ID and language disorders because both are strongly associated with challenging behaviors and mental disorder. Because early intervention is associated with optimal outcomes, child psychiatrists must be aware of their signs and symptoms, particularly as related to delays in cognitive and adaptive function. Optimal management of both ID and language disorders requires a multidisciplinary, team-based, and family centered approach. Child psychiatrists play an important role on this team, given their expertise with contextualizing and treating challenging behaviors. © 2017 Elsevier Inc.


Author Keywords
Early intervention;  Global developmental delay;  Intellectual disability;  Language disorder;  Multidisciplinary care


Document Type: Review
Source: Scopus

 

12) 

Bailey, H.R., Kurby, C.A., Sargent, J.Q., Zacks, J.M.
Attentional focus affects how events are segmented and updated in narrative reading
(2017) Memory and Cognition, pp. 1-16. Article in Press. 

DOI: 10.3758/s13421-017-0707-2


a Kansas State University, 414 Bluemont Hall, Manhattan, KS, United States
b Washington University, St. Louis, MO, United States
c Grand Valley State University, Allendale, MI, United States
d Francis Marion University, Florence, SC, United States


Abstract
Readers generate situation models representing described events, but the nature of these representations may differ depending on the reading goals. We assessed whether instructions to pay attention to different situational dimensions affect how individuals structure their situation models (Exp. 1) and how they update these models when situations change (Exp. 2). In Experiment 1, participants read and segmented narrative texts into events. Some readers were oriented to pay specific attention to characters or space. Sentences containing character or spatial-location changes were perceived as event boundaries—particularly if the reader was oriented to characters or space, respectively. In Experiment 2, participants read narratives and responded to recognition probes throughout the texts. Readers who were oriented to the spatial dimension were more likely to update their situation models at spatial changes; all readers tracked the character dimension. The results from both experiments indicated that attention to individual situational dimensions influences how readers segment and update their situation models. More broadly, the results provide evidence for a global situation model updating mechanism that serves to set up new models at important narrative changes. © 2017 Psychonomic Society, Inc.


Author Keywords
Event segmentation;  Global updating;  Incremental updating;  Situation model updating;  Text comprehension


Document Type: Article in Press
Source: Scopus

 

13) 

Purtle, J., Lê-Scherban, F., Shattuck, P., Proctor, E.K., Brownson, R.C.
An audience research study to disseminate evidence about comprehensive state mental health parity legislation to US State policymakers: Protocol
(2017) Implementation Science, 12 (1), art. no. 81, . 

DOI: 10.1186/s13012-017-0613-9


a Drexel University, Department of Health Management and Policy, Dornsife School of Public Health, 3215 Market St, Philadelphia, PA, United States
b Drexel University, Department of Epidemiology and Biostatistics, Dornsife School of Public Health, 3215 Market St, Philadelphia, PA, United States
c Drexel University, A.J. Drexel Autism Institute, 3215 Market St, Philadelphia, PA, United States
d Washington University in St. Louis, Center for Mental Health Services Research, Brown School of Social Work, St. Louis, MO, United States
e Washington University in St. Louis, Prevention Research Center in St. Louis, Brown School of Social Work, St. Louis, MO, United States
f Washington University School of Medicine, Washington University in St. Louis, Division of Public Health Sciences and Alvin J. Siteman Cancer Center, St. Louis, MO, United States


Abstract
Background: A large proportion of the US population has limited access to mental health treatments because insurance providers limit the utilization of mental health services in ways that are more restrictive than for physical health services. Comprehensive state mental health parity legislation (C-SMHPL) is an evidence-based policy intervention that enhances mental health insurance coverage and improves access to care. Implementation of C-SMHPL, however, is limited. State policymakers have the exclusive authority to implement C-SMHPL, but sparse guidance exists to inform the design of strategies to disseminate evidence about C-SMHPL, and more broadly, evidence-based treatments and mental illness, to this audience. The aims of this exploratory audience research study are to (1) characterize US State policymakers' knowledge and attitudes about C-SMHPL and identify individual- and state-level attributes associated with support for C-SMHPL; and (2) integrate quantitative and qualitative data to develop a conceptual framework to disseminate evidence about C-SMHPL, evidence-based treatments, and mental illness to US State policymakers. Methods: The study uses a multi-level (policymaker, state), mixed method (QUAN→qual) approach and is guided by Kingdon's Multiple Streams Framework, adapted to incorporate constructs from Aarons' Model of Evidence-Based Implementation in Public Sectors. A multi-modal survey (telephone, post-mail, e-mail) of 600 US State policymakers (500 legislative, 100 administrative) will be conducted and responses will be linked to state-level variables. The survey will span domains such as support for C-SMHPL, knowledge and attitudes about C-SMHPL and evidence-based treatments, mental illness stigma, and research dissemination preferences. State-level variables will measure factors associated with C-SMHPL implementation, such as economic climate and political environment. Multi-level regression will determine the relative strength of individual- and state-level variables on policymaker support for C-SMHPL. Informed by survey results, semi-structured interviews will be conducted with approximately 50 US State policymakers to elaborate upon quantitative findings. Then, using a systematic process, quantitative and qualitative data will be integrated and a US State policymaker-focused C-SMHPL dissemination framework will be developed. Discussion: Study results will provide the foundation for hypothesis-driven, experimental studies testing the effects of different dissemination strategies on state policymakers' support for, and implementation of, evidence-based mental health policy interventions. © 2017 The Author(s).


Author Keywords
Audience research;  Dissemination;  Parity legislation;  Policy dissemination research;  US State policymakers


Document Type: Article
Source: Scopus

 

14) 

Dai, C., Lehar, M., Sun, D.Q., RVT, L.S., Carey, J.P., MacLachlan, T., Brough, D., Staecker, H., della Santina, A.M., Hullar, T.E., della Santina, C.C.
Rhesus Cochlear and Vestibular Functions Are Preserved After Inner Ear Injection of Saline Volume Sufficient for Gene Therapy Delivery
(2017) JARO - Journal of the Association for Research in Otolaryngology, pp. 1-17. Article in Press. 

DOI: 10.1007/s10162-017-0628-6


a Vestibular NeuroEngineering Lab, Department of Otolaryngology–Head & Neck Surgery, Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross Bldg Rm 830, Baltimore, MD, United States
b Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross Bldg Rm 830, Baltimore, MD, United States
c Novartis Institutes for Biomedical Research, 250 Massachusetts Ave, Cambridge, MA, United States
d GenVec, 910 Clopper Rd #220n, Gaithersburg, MD, United States
e Dept of Otolaryngology, Head & Neck Surgery, University of Kansas School of Medicine, 3901 Rainbow Blvd, Kansas City, KS, United States
f Department of Otolaryngology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, United States
g Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, United States
h Department of Audiology and Communication Sciences, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, United States


Abstract
Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome. The primary goal of the present study was to assess that risk in rhesus monkeys, which closely approximates humans with regard to middle and inner ear anatomy. Secondary goals were to identify the best delivery route into the primate ear from among two common surgical approaches (i.e., via an oval window stapedotomy and via the round window) and to determine the relative volumes of rhesus, rodent, and human labyrinths for extrapolation of results to other species. We measured hearing and vestibular functions before and 2, 4, and 8 weeks after unilateral injection of phosphate-buffered saline vehicle (PBSV) into the perilymphatic space of normal rhesus monkeys at volumes sufficient to deliver an atoh1 gene therapy vector. To isolate effects of injection, PBSV without vector was used. Assays included behavioral observation, auditory brainstem responses, distortion product otoacoustic emissions, and scleral coil measurement of vestibulo-ocular reflexes during whole-body rotation in darkness. Three groups (N = 3 each) were studied. Group A received a 10 μL transmastoid/trans-stapes injection via a laser stapedotomy. Group B received a 10 μL transmastoid/trans-round window injection. Group C received a 30 μL transmastoid/trans-round window injection. We also measured inner ear fluid space volume via 3D reconstruction of computed tomography (CT) images of adult C57BL6 mouse, rat, rhesus macaque, and human temporal bones (N = 3 each). Injection was well tolerated by all animals, with eight of nine exhibiting no signs of disequilibrium and one animal exhibiting transient disequilibrium that resolved spontaneously by 24 h after surgery. Physiologic results at the final, 8-week post-injection measurement showed that injection was well tolerated. Compared to its pretreatment values, no treated ear’s ABR threshold had worsened by more than 5 dB at any stimulus frequency; distortion product otoacoustic emissions remained detectable above the noise floor for every treated ear (mean, SD and maximum deviation from baseline: −1.3, 9.0, and −18 dB, respectively); and no animal exhibited a reduction of more than 3 % in vestibulo-ocular reflex gain during high-acceleration, whole-body, passive yaw rotations in darkness toward the treated side. All control ears and all operated ears with definite histologic evidence of injection through the intended site showed similar findings, with intact hair cells in all five inner ear sensory epithelia and intact auditory/vestibular neurons. The relative volumes of mouse, rat, rhesus, and human inner ears as measured by CT were (mean ± SD) 2.5 ± 0.1, 5.5 ± 0.4, 59.4 ± 4.7 and 191.1 ± 4.7 μL. These results indicate that injection of PBSV at volumes sufficient for gene therapy delivery can be accomplished without destruction of inner ear structures required for hearing and vestibular sensation. © 2017 Association for Research in Otolaryngology


Author Keywords
auditory brainstem response;  gene therapy;  inner ear;  otoacoustic emission;  safety;  vestibular ocular reflex;  volume


Document Type: Article in Press
Source: Scopus

 

15) 

Molitoris, J.K., Rao, Y.J., Patel, R.A., Kane, L.T., Badiyan, S.N., Gittleman, H., Barnholtz-Sloan, J.S., Bentzen, S.M., Kruser, T.J., Huang, J., Mehta, M.P.
Multi-institutional external validation of a novel glioblastoma prognostic nomogram incorporating MGMT methylation
(2017) Journal of Neuro-Oncology, pp. 1-8. Article in Press. 

DOI: 10.1007/s11060-017-2529-2


a Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, United States
b Radiation Oncology, Washington University, St. Louis, MO, United States
c Radiation Oncology, Northwestern University, Chicago, IL, United States
d Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States
e Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States
f Miami Cancer Institute, Radiation Oncology Executive Office, 8900 N. Kendall Drive, 1st Floor, Rm 1RC06, Miami, FL, United States


Abstract
A recent nomogram for glioblastoma (GBM) was designed to incorporate methylguanine-DNA methyltransferase (MGMT) methylation status in trial patients receiving temozolomide. Since clinical trial patients are strictly selected, compared to the general population, we performed a multi-institutional, external, independent assessment of the nomogram. Consecutive adult patients with supratentorial GBM diagnosed between June 2007 and December 2014 who initiated TMZ-based concurrent chemoradiotherapy (CRT) and were not enrolled on RTOG 0525 or 0825 were eligible. We collected age, gender, MGMT status, performance status, resection extent, race, and tumor site and Cox regression analysis of overall survival (OS) was conducted with the 1-year nomogram-predicted survival (NPS). The predictive accuracy was quantified by the concordance index (c-index) as well as by separating patients into quintile-groups of the population distribution of NPS and comparing mean NPS and observed OS. Of 514 patients with GBM, 309 had all nomogram factors. Median OS was 18.7 months. NPS and observed OS demonstrated a c-index of 0.695. On univariate analysis, the NPS and all included factors except gender were significant. On multivariable analysis (MVA) the only significant factor for worse survival was lower NPS. When separated into quintile-groups of NPS, the observed survival was slightly better than the predicted survival for all but the worst prognostic group. Our multi-institutional cohort provides independent external validation of a novel GBM nomogram incorporating MGMT methylation status. No individual factor included in the nomogram retained significance on MVA after adjusting for NPS. © 2017 Springer Science+Business Media, LLC


Author Keywords
Glioblastoma;  Nomogram;  O6-Methylguanine-DNA methyltransferase;  Survival


Document Type: Article in Press
Source: Scopus

 

16) 

Dhar, R., Misra, H., Diringer, M.N.
SANGUINATE™ (PEGylated Carboxyhemoglobin Bovine) Improves Cerebral Blood Flow to Vulnerable Brain Regions at Risk of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage
(2017) Neurocritical Care, pp. 1-9. Article in Press. 

DOI: 10.1007/s12028-017-0418-3


a Department of Neurology (Division of Neurocritical Care), Washington University School of Medicine in St. Louis, 660 S. Euclid Avenue, Campus Box 8111, St. Louis, MO, United States
b Prolong Pharmaceuticals, 300 Corporate Court, South Plainfield, NJ, United States


Abstract
Background: Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been linked to focal reductions in cerebral blood flow (CBF) and microvascular impairments in oxygen delivery. Effective therapies that restore flow and oxygen transport to vulnerable brain regions are currently lacking. SANGUINATE is a dual-action carbon monoxide-releasing and hemoglobin-based oxygen transfer agent with efficacy in animal models of focal brain ischemia and tolerability in patients with sickle cell disease. Methods: We performed a safety and proof-of-principle study in 12 SAH patients at risk of DCI across three escalating doses (160, 240, and 320 mg/kg). We used 15O-PET (performed at baseline, after SANGUINATE and at 24 h) to evaluate efficacy for improving CBF and restoring flow–metabolism balance (assessed by oxygen extraction fraction [OEF]) to vulnerable regions (defined as baseline OEF ≥ 0.50). Results: SANGUINATE resulted in a transient rise in mean arterial pressure (116 ± 15–127 ± 13 mm Hg, p = 0.001) that normalized by 24 h and allowed three patients with DCI to be weaned off vasopressors. No adverse events were noted during infusion. Global CBF did not rise (43 ± 8–46 ± 9 ml/100 g/min) although a trend was seen at the highest dose (45 ± 7–51 ± 9, p = 0.044). However, a significant 16% rise in regional CBF associated with reduction in OEF was seen in vulnerable regions, but did not persist at 24 h. Conclusions: We demonstrated that this novel agent can improve regional CBF and may improve oxygen supply–demand balance. Clinical studies (likely with repeat dosing) are required to evaluate whether this effect can prevent DCI or cerebral infarction. © 2017 Springer Science+Business Media New York


Author Keywords
Brain ischemia;  Cerebral blood flow;  Subarachnoid hemorrhage;  Vasospasm


Document Type: Article in Press
Source: Scopus

 

17) 

Sebe, J.Y., Cho, S., Sheets, L., Rutherford, M.A., von Gersdorff, H., Raible, D.W.
Ca2+-permeable AMPARs mediate glutamatergic transmission and excitotoxic damage at the hair cell ribbon synapse
(2017) Journal of Neuroscience, 37 (25), pp. 6162-6175. 

DOI: 10.1523/JNEUROSCI.3644-16.2017


a Departments of Biology and Biological Structure, University of Washington, Seattle, WA, United States
b Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE, United States
c Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Department of Otolaryngology, Harvard Medical School, Boston, MA, United States
d Department of Otolaryngology, Washington University in St. Louis, St. Louis, MO, United States
e The Vollum Institute, Oregon Health & Science University, Portland, OR, United States


Abstract
We report functional and structural evidence for GluA2-lacking Ca2+-permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immuno his to chemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss. © 2017 the authors.


Author Keywords
Cochlear synaptopathy;  Excitotoxicity;  GCaMP;  Noise overexposure;  Zebrafish


Document Type: Article
Source: Scopus

 

18) 

Lebois, E.P. 5.83", Schroeder, J.P., Esparza, T.J., Bridges, T.M., Lindsley, C.W., Conn, P.J., Brody, D.L., Daniels, J.S., Levey, A.I.
Disease-Modifying Effects of M1 Muscarinic Acetylcholine Receptor Activation in an Alzheimer's Disease Mouse Model
(2017) ACS Chemical Neuroscience, 8 (6), pp. 1177-1187. 

DOI: 10.1021/acschemneuro.6b00278


a Department of Neurology, Emory University, Atlanta, GA, United States
b Center for Neurodegenerative Disease, Emory University, Atlanta, GA, United States
c Department of Neurology, Washington University, St. Louis, MO, United States
d Department of Pharmacology, Vanderbilt University, Nashville, TN, United States
e Department of Chemistry, Vanderbilt University, Nashville, TN, United States
f Vanderbilt Center for Neuroscience Drug Discovery, Nashville, TN, United States
g Alzheimer's Disease Research Center, Emory University, Atlanta, GA, United States
h Neuroscience and Pain Research Unit Circuits, Neurotransmitters, and Signaling Division Pfizer, Inc., Cambridge, MA, United States


Abstract
Alzheimer's disease (AD) is the leading cause of dementia worldwide, and currently no disease-modifying therapy is available to slow or prevent AD, underscoring the urgent need for neuroprotective therapies. Selective M1 muscarinic acetylcholine receptor (mAChR) activation is an attractive mechanism for AD therapy since M1 mediates key effects on memory, cognition, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation. To validate M1 as a neuroprotective treatment target for AD, the M1-selective agonist, VU0364572, was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology (2 months) to an age where these mice are known to display memory impairments (6 months). Chronic M1 activation prevented mice from becoming memory-impaired, as measured by Morris water maze (MWM) testing at 6 months of age. Additionally, M1 activation significantly reduced levels of soluble and insoluble Aβ40,42 in the cortex and hippocampus of these animals, as measured by ELISA and immunohistochemistry. Moreover, soluble hippocampal Aβ42 levels were strongly correlated with MWM memory impairments and M1 activation with VU0364572 abolished this correlation. Finally, VU0364572 significantly decreased oligomeric (oAβ) levels in the cortex, suggesting one mechanism whereby VU0364572 may be exerting its neuroprotective effects is by reducing the available oAβ pool in the brain. These findings suggest that chronic M1 activation has neuroprotective potential for preventing memory impairments and reducing neuropathology in AD. M1 activation therefore represents a promising avenue for preventative treatment, as well as a promising opportunity to combine symptomatic and disease-modifying effects for early AD treatment. © 2017 American Chemical Society.


Author Keywords
acetylcholine;  Alzheimer's;  amyloid;  hippocampus;  memory;  Muscarinic


Document Type: Article
Source: Scopus

 

19) 

Ross, S.A., Yount, M., Ankarstad, S., Bock, S., Orso, B., Perry, K., Miros, J., Brunstrom-Hernandez, J.E.
Effects of Participation in Sports Programs on Walking Ability and Endurance Over Time in Children With Cerebral Palsy
(2017) American Journal of Physical Medicine and Rehabilitation, . Article in Press. 

DOI: 10.1097/PHM.0000000000000767


From the Maryville University, St. Louis, Missouri (SAR, MY, SA, SB, BO, KP); and Washington University and St. Louis Children's Hospital, St. Louis, Missouri (JM, JEB-H).


Abstract
OBJECTIVE: Children with cerebral palsy may benefit from maintaining a high level of physical fitness similar to typically developing children especially in terms of long-term physical performance, although in practice this is often difficult. The purpose of this study was to determine the effect of participation in sports programs on walking ability and endurance over time. DESIGN: A retrospective cohort study included participants with cerebral palsy, aged 6 to 20 yrs, who attended a summer sports program from 2004 to 2012. There were 256 participant sessions with pre/post data recorded. The participants consisted of a total of 97 children (mean age [SD] = 11.4 [3.1] yrs), many of whom attended multiple programs throughout the years. Programs were held 6 hrs/d, 5 d/wk for up to 4 wks. Outcome measures included the Timed Up and Go, modified 6-min walk, and 25-ft walk/run. RESULTS: The results showed significant improvements in the Timed Up and Go, modified 6-min walk distance and 25-ft walk/run over time. Children in Gross Motor Classification System level III made the largest gains. CONCLUSIONS: Walking ability and endurance seem to improve after participation in an intensive summer sports programs. Higher frequency of program attendance resulted in significant improvements in the Timed Up and Go. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Discuss the importance of physical activity at the participation level (sports programs) for children with cerebral palsy; (2) Contrast the changes in walking ability and endurance for children in Gross Motor Function Classification System level I, II, and III after sports programs; and (3) Identify the impact of higher frequency of sports program attendance over time on walking ability. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Document Type: Article in Press
Source: Scopus

 

20) 

Estes, A., Munson, J., John, T.S., Dager, S.R., Rodda, A., Botteron, K., Hazlett, H., Schultz, R.T., Zwaigenbaum, L., Piven, J., Guralnick, M.J., The Ibis Network, Piven, J., Hazlett, H.C., Chappell, J.C., Dager, S., Estes, A., Shaw, D., Botteron, K., McKinstry, R., Constantino, J., Pruett, J., Schultz, R., Paterson, S., Zwaigenbaum, L., Evans, A.C., Collins, D.L., Pike, G.B., Kostopolous, P., Das, S., Gerig, G., Styner, M., Gu, H., Sullivan, P., Wright, F.
Parent Support of Preschool Peer Relationships in Younger Siblings of Children with Autism Spectrum Disorder
(2017) Journal of Autism and Developmental Disorders, pp. 1-11. Article in Press. 

DOI: 10.1007/s10803-017-3202-5


a Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, United States
b Department of Psychology, University of Washington, Seattle, WA, United States
c Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States
d Department of Radiology, University of Washington, Seattle, WA, United States
e Department of Psychiatry, Washington University, St. Louis, MO, United States
f Carolina Institute for Developmental Disabilities, Chapel Hill, NC, United States
g The Center for Autism Research, Department of Pediatrics, Children’s Hospital of Pennsylvania, University of Pennsylvania, Philadelphia, PA, United States
h Department of Pediatrics, University of Alberta, Edmonton, AB, Canada


Abstract
Preschool-aged siblings of children with ASD are at high-risk (HR) for ASD and related challenges, but little is known about their emerging peer competence and friendships. Parents are the main providers of peer-relationship opportunities during preschool. Understanding parental challenges supporting early peer relationships is needed for optimal peer competence and friendships in children with ASD. We describe differences in peer relationships among three groups of preschool-aged children (15 HR-ASD, 53 HR-NonASD, 40 low-risk, LR), and examine parent support activities at home and arranging community-based peer activities. Children with ASD demonstrated precursors to poor peer competence and friendship outcomes. Parents in the HR group showed resilience in many areas, but providing peer opportunities for preschool-age children with ASD demanded significant adaptations. © 2017 Springer Science+Business Media, LLC


Author Keywords
Autism;  High risk;  Parent;  Peer relations;  Preschool;  Sibling


Document Type: Article in Press
Source: Scopus

 

21) 

Treiman, R.
Learning to spell: Phonology and beyond
(2017) Cognitive Neuropsychology, pp. 1-11. Article in Press. 

DOI: 10.1080/02643294.2017.1337630


Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, USA


Abstract
An understanding of the nature of writing systems and of the typical course of spelling development is an essential foundation for understanding the problems of children who have serious difficulties in learning to spell. The present article seeks to provide that foundation. It argues that the dual-route models of spelling that underlie much existing research and practice are based on overly simple assumptions about how writing systems work and about how spelling skills develop. Many writing systems include not only context-free links from phonemes to letters but also context-sensitive phonological patterns, morphological influences, and graphotactic patterns. According to an alternative framework, IMP (integration of multiple patterns), spellers acquire multiple sources of information through use of their statistical-learning skills and through direct instruction. Children learn the spelling of a word most easily when different patterns converge on the spelling, and they have difficulty when patterns conflict. Implications of these ideas for assessment and instruction are considered. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
graphotactics;  morphology;  phonology;  Spelling;  spelling models


Document Type: Article in Press
Source: Scopus

 

22) 

Wang, S., Borschel, W.F., Heyman, S., Hsu, P., Nichols, C.G.
Conformational changes at cytoplasmic intersubunit interactions control Kir channel gating
(2017) Journal of Biological Chemistry, 292 (24), pp. 10087-10096. 

DOI: 10.1074/jbc.M117.785154


Department of Cell Biology and Physiology, Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO, United States


Abstract
The defining structural feature of inward-rectifier potassium (Kir) channels is the unique Kir cytoplasmic domain. Recently we showed that salt bridges located at the cytoplasmic domain subunit interfaces (CD-Is) of eukaryotic Kir channels control channel gating via stability of a novel inactivated closed state. The cytoplasmic domains of prokaryotic and eukaryotic Kir channels show similar conformational rearrangements to the common gating ligand, phosphatidylinositol bisphosphate (PIP2), although these exhibit opposite coupling to opening and closing transitions. In Kir2.1, mutation of one of these CD-I salt bridge residues (R204A) reduces apparent PIP2 sensitivity of channel activity, and here we show that Ala or Cys substitutions of the functionally equivalent residue (Arg-165) in the prokaryotic Kir channel KirBac1.1 also significantly decrease sensitivity of the channel to PIP2 (by 5-30-fold). To further understand the structural basis of CD-I control of Kir channel gating, we examined the effect of the R165A mutation on PIP2-induced changes in channel function and conformation. Single-channel analyses indicated that the R165A mutation disrupts the characteristic long interburst closed state of reconstituted KirBac1.1 in giant liposomes, resulting in a higher open probability due to more frequent opening bursts. Intramolecular FRET measurements indicate that, relative to wild-type channels, the R165A mutation results in splaying of the cytoplasmic domains away from the central axis and that PIP2 essentially induces opposite motions of the major β-sheet in this channel mutant. We conclude that the removal of stabilizing CD-I salt bridges results in a collapsed state of the Kir domain. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.


Document Type: Article
Source: Scopus

 

23) 

Scherer, S.L., Cain, M.D., Kanai, S.M., Kaltenbronn, K.M., Blumer, K.J.
Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13
(2017) Journal of Biological Chemistry, 292 (24), pp. 9906-9918. 

DOI: 10.1074/jbc.M116.771923


Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO, United States


Abstract
The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G1/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G1/o signaling. Accordingly, we used tandem affinity purification and LCMS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα13·R7-RGS complexes. Because Gα13/R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ5 with or without R7BP. We found that neurite retraction evoked by Gα12/13-dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα12/13 but not G1/o. These findings provide the first evidence that R7-RGS heterotrimers interact with Gα13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.


Document Type: Article
Source: Scopus

 

24) 

Kornfield, S.L., Moseley, M., Appleby, D., McMickens, C.L., Sammel, M.D., Epperson, C.N.
Posttraumatic Symptom Reporting and Reported Cigarette Smoking during Pregnancy
(2017) Journal of Women's Health, 26 (6), pp. 662-669. 

DOI: 10.1089/jwh.2016.5928


a Department of Psychiatry, Washington University, School of Medicine, Campus Box 8134, 600 S. Euclid Avenue, St. Louis, MO, United States
b Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
c Penn Center for Women's Behavioral Wellness, Philadelphia, PA, United States
d Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
e Robert Wood Johnson Foundation Clinical Scholars Program, Yale University, School of Medicine, New Haven, CT, United States
f Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States


Abstract
Introduction: Increased prevalence of nicotine dependence among individuals suffering from posttraumatic stress disorder (PTSD) is well established. However, there are limited studies on the prevalence of smoking during pregnancy in relation to prepregnancy history of trauma exposures and active PTSD symptoms during pregnancy. Prenatal smoking has been implicated in a host of negative outcomes for mother and baby. Given maternal and fetal risk, it is critical to define predictors of continued cigarette smoking during pregnancy. Methods: Pregnant women from an urban perinatal clinic completed an anonymous survey of trauma history using a modified Traumatic Life Events Questionnaire (TLEQ), PTSD symptoms using the PTSD Symptom Checklist - Civilian Version (PCL-C) and current and past smoking behavior. Those who smoked any number of cigarettes per day after pregnancy confirmation were considered to be "pregnant smokers." Results: Of 218 women who completed the survey, 34 (15.6%) reported smoking cigarettes after confirmation of pregnancy. In unadjusted models, trauma exposure that resulted in fear, helplessness, or horror (FHH), as well as current PTSD symptom severity and probable PTSD diagnosis showed statistical significance as predictors of smoking during pregnancy. After adjusting for age only, PTSD symptoms retained their significant association with smoking during pregnancy. When history of smoking at least five cigarettes per day was added to our models, none of the associations remained significant. Conclusions: These findings emphasize the importance of the behavioral response to past traumatic exposures in influencing cigarette smoking behavior before pregnancy. Given such behaviors enhance risk for continued tobacco use during pregnancy, a trauma-informed approach to smoking cessation in preconception care may ultimately reduce the likelihood of smoking during pregnancy and requires further study. © 2017, Mary Ann Liebert, Inc.


Author Keywords
obstetrics;  pregnancy;  PTSD;  smoking


Document Type: Article
Source: Scopus

 

25) 

Lee, H., Park, S.
Gender differences in the trajectory classes of depressive symptoms in Korean older adults
(2017) Aging and Mental Health, pp. 1-8. Article in Press. 

DOI: 10.1080/13607863.2017.1339776


a Department of Social Welfare, Daegu University, Gyeongsan-si, Republic of Korea
b George Warren Brown School of Social Work, Washington University in Saint Louis, St. Louis, MO, USA


Abstract
Objectives: This study aimed (1) to identify gender-specific heterogeneous longitudinal patterns of depressive symptoms, (2) to explore the effects of economic status and various health conditions as risk factors in depressive symptom trajectories. Method: Data came from the Korean Longitudinal Study of Aging (2006–2012) focuing on older adults aged 65 and older. Latent class growth analysis was used to identify the depressive symptom trajectory groups. Multinomial logistic regression was used to examine the association between economic and health status changes and the depresison trajectories. Results: Among older women, three change groups were identified: stable low, stable high, and moderate but slightly increasing groups. Among older men, four groups were found: stable low, moderate but rapidly increasing, high but decreasing, and moderate but slightly increasing groups. Among women, poverty experience and sustained poor health, particularly constantly low cognition, were significantly associated with the stable high group. Among men, deteriorating economic and health status were significant predictors of membership in the most vulnerable subgroup, the moderate but rapidly increasing group. Conclusion: This study demonstrated among older adults, depressive symptoms change heterogeneously by gender. Identification of the most at risk subgroups among older men and women provides important initial empirical information to target clinical programs and policy development. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
Depressive symptoms;  gender difference;  growth mixture model


Document Type: Article in Press
Source: Scopus

 

26) 

Tang, Y.-Y., Jiang, C., Tang, R.
How mind-body practice works-integration or separation?
(2017) Frontiers in Psychology, 8 (MAY), art. no. 866, . 

DOI: 10.3389/fpsyg.2017.00866


a Department of Psychological Sciences, Texas Tech University, Lubbock, TX, United States
b Beijing Key Lab of Physical Fitness Evaluation and Tech Analysis, Capital University of Physical Education and Sports, Beijing, China
c Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States


Author Keywords
Autonomic nervous system;  Central nervous system;  Integrative body-mind training (IBMT);  MBCT;  MBSR;  Mind-body practice;  Mindfulness meditation


Document Type: Note
Source: Scopus

 

27) 

Li, R., Hao, J., Fujiwara, H., Xu, M., Yang, S., Dai, S., Long, Y., Swaroop, M., Li, C., Vu, M., Marugan, J.J., Ory, D.S., Zheng, W.
Analytical Characterization of Methyl-β-Cyclodextrin for Pharmacological Activity to Reduce Lysosomal Cholesterol Accumulation in Niemann-Pick Disease Type C1 Cells
(2017) Assay and Drug Development Technologies, 15 (4), pp. 154-166. 

DOI: 10.1089/adt.2017.774


a National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD, United States
b Poochon Scientific, Frederick, MD, United States
c Diabetic Cardiovascular Disease Center, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
Methyl-β-cyclodextrin (MβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MβCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MβCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MβCDs. Our data revealed varied mass spectrum profiles and pharmacological activities on the reduction of lysosomal cholesterol accumulation in NPC1 fibroblasts for these three preparations of MβCDs obtained from different batches and different sources. Furthermore, a proteomic analysis showed the differences of these three MβCD preparations on amelioration of dysregulated protein expression levels in NPC1 cells. The results demonstrate the importance of prescreening of different cyclodextrin preparations before use as a therapeutic agent. A combination of mass spectrum analysis, measurement of pharmacological activity, and proteomic profiling provides an effective analytical procedure for characterization of cyclodextrins for therapeutic applications. © 2017 Mary Ann Liebert, Inc.


Author Keywords
Lysosomal storage disease;  mass spectrometry;  methyl-b-cyclodextrin;  niemann-pick disease type C1;  proteomics


Document Type: Article
Source: Scopus

 

28) 

Gratton, C., Yousef, S., Aarts, E., Wallace, D.L., D'Esposito, M., Silver, M.A.
Cholinergic, But Not Dopaminergic or Noradrenergic, Enhancement Sharpens Visual Spatial Perception in Humans
(2017) The Journal of neuroscience : the official journal of the Society for Neuroscience, 37 (16), pp. 4405-4415. 

DOI: 10.1523/JNEUROSCI.2405-16.2017


a Neurology Department, Washington University, St. Louis, Missouri 63110,
b School of Optometry, University of California, Berkeley, California 94720
c Vision Science Graduate Group, University of California, Berkeley, California 94720
d Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen 6525 EN, The Netherlands
e Department of Neurosurgery, University of California, San Francisco, California 94122, and
f Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720


Abstract
The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker distance. We found that cholinergic enhancement with the cholinesterase inhibitor donepezil improved target detection, and modeling suggested that this was mainly due to a narrowing of the extent of facilitatory perceptual spatial interactions. In Experiment 2, we tested whether these effects were selective to the cholinergic system or would also be observed following enhancements of related neuromodulators dopamine or norepinephrine. Unlike cholinergic enhancement, dopamine (bromocriptine) and norepinephrine (guanfacine) manipulations did not improve performance or systematically alter the spatial profile of perceptual interactions between targets and distractors. These findings reveal mechanisms by which cholinergic signaling influences visual spatial interactions in perception and improves processing of a visual target among distractors, effects that are notably similar to those of spatial selective attention.SIGNIFICANCE STATEMENT Acetylcholine influences how visual cortical neurons integrate signals across space, perhaps providing a neurobiological mechanism for the effects of visual selective attention. However, the influence of cholinergic enhancement on visuospatial perception remains unknown. Here we demonstrate that cholinergic enhancement improves detection of a target flanked by distractors, consistent with sharpened visuospatial perceptual representations. Furthermore, whereas most pharmacological studies focus on a single neurotransmitter, many neuromodulators can have related effects on cognition and perception. Thus, we also demonstrate that enhancing noradrenergic and dopaminergic systems does not systematically improve visuospatial perception or alter its tuning. Our results link visuospatial tuning effects of acetylcholine at the neuronal and perceptual levels and provide insights into the connection between cholinergic signaling and visual attention. Copyright © 2017 the authors 0270-6474/17/374405-11$15.00/0.


Author Keywords
acetylcholine;  attention;  dopamine;  norepinephrine;  pharmacology;  visuospatial perception


Document Type: Article
Source: Scopus



29) 

Papadimitriou, C., White, R.L., 3rd, Snyder, L.H.
Ghosts in the Machine II: Neural Correlates of Memory Interference from the Previous Trial
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (4), pp. 2513-2527. Cited 1 time.

DOI: 10.1093/cercor/bhw106


a Department of Anatomy and Neurobiology, Washington University in St. Louis, St. Louis, MO 63116, USA
b Department of Psychology, University of California Berkeley, Berkeley, CA 94720, USA


Abstract
Previous memoranda interfere with working memory. For example, spatial memories are biased toward locations memorized on the previous trial. We predicted, based on attractor network models of memory, that activity in the frontal eye fields (FEFs) encoding a previous target location can persist into the subsequent trial and that this ghost will then bias the readout of the current target. Contrary to this prediction, we find that FEF memory representations appear biased away from (not toward) the previous target location. The behavioral and neural data can be reconciled by a model in which receptive fields of memory neurons converge toward remembered locations, much as receptive fields converge toward attended locations. Convergence increases the resources available to encode the relevant memoranda and decreases overall error in the network, but the residual convergence from the previous trial can give rise to an attractive behavioral bias on the next trial. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


Author Keywords
attractor network models;  frontal eye fields;  proactive interference;  receptive field remapping;  spatial working memory


Document Type: Article
Source: Scopus

 

30) 

Adhikari, M.H., Hacker, C.D., Siegel, J.S., Griffa, A., Hagmann, P., Deco, G., Corbetta, M.
Decreased integration and information capacity in stroke measured by whole brain models of resting state activity
(2017) Brain : a journal of neurology, 140 (4), pp. 1068-1085. 

DOI: 10.1093/brain/awx021


a Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Ramon Trias Fargas, 25-27, Barcelona, 08005, Spain
b Department of Bioengineering, Washington University Saint Louis, USA
c Department of Neurology, Washington University School of Medicine Saint Louis, USA
d Department of Radiology, Lausanne University Hospital and University of Lausanne (CHUV-UNIL), 1011 Lausanne, Switzerland
e Signal Processing Lab 5, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland
f Institucio Catalana de la Recerca I Estudis Avancats (ICREA), University of Pompeu Fabra, Passeig Lluis Companys 23, Barcelona, 08010, Spain
g Departments of Radiology and Neuroscience, Washington University School of Medicine Saint Louis, USA
h Department of Neuroscience, University of Padua, Italy


Abstract
While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to represent stimuli and task states, and that information capacity measured through whole brain models is a theory-driven measure of processing capacity that could be used as a biomarker of injury for outcome prediction or target for rehabilitation intervention. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.


Author Keywords
functional connectivity;  information capacity;  integration;  whole-brain modelling


Document Type: Article
Source: Scopus

 

31) 

Gratton, C., Neta, M., Sun, H., Ploran, E.J., Schlaggar, B.L., Wheeler, M.E., Petersen, S.E., Nelson, S.M.
Distinct Stages of Moment-to-Moment Processing in the Cinguloopercular and Frontoparietal Networks
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (3), pp. 2403-2417. 

DOI: 10.1093/cercor/bhw092


a Department of Neurology
b Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA
c Department of Biomedical Engineering
d Department of Psychology, Hofstra University, Hempstead, NY, USA
e Department of Radiology
f Department of Pediatrics
g Department of Neuroscience
h School of Psychology, Georgia Institute of Technology, Atlanta, GA, USA
i Department of Psychology and
j Department of Neurological Surgery, Washington University in St Louis, St Louis, MO, USA
k VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA
l Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA


Abstract
Control of goal-directed tasks is putatively carried out via the cinguloopercular (CO) and frontoparietal (FP) systems. However, it remains unclear whether these systems show dissociable moment-to-moment processing during distinct stages of a trial. Here, we characterize dynamics in the CO and FP networks in a meta-analysis of 5 decision-making tasks using fMRI, with a specialized "slow reveal" paradigm which allows us to measure the temporal characteristics of trial responses. We find that activations in left FP, right FP, and CO systems form separate clusters, pointing to distinct roles in decision-making. Left FP shows early "accumulator-like" responses, suggesting a role in pre-decision processing. CO has a late onset and transient response linked to the decision event, suggesting a role in performance reporting. The majority of right FP regions show late onsets with prolonged responses, suggesting a role in post-recognition processing. These findings expand upon past models, arguing that the CO and FP systems relate to distinct stages of processing within a trial. Furthermore, the findings provide evidence for a heterogeneous profile in the FP network, with left and right FP taking on specialized roles. This evidence informs our understanding of how distinct control networks may coordinate moment-to-moment components of complex actions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


Author Keywords
decision-making;  executive control;  fMRI;  networks


Document Type: Article
Source: Scopus

 

32) 

Neta, M., Nelson, S.M., Petersen, S.E.
Dorsal Anterior Cingulate, Medial Superior Frontal Cortex, and Anterior Insula Show Performance Reporting-Related Late Task Control Signals
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (3), pp. 2154-2165. 

DOI: 10.1093/cercor/bhw053


a Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE68588, USA
b VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX 76711, USA
c Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX 75235, USA
d Department of Neurology
e Department of Psychology
f Department of Radiology
g Department of Anatomy and Neurobiology
h Department of Neurosurgery
i Biomedical Engineering, Washington University, St. Louis, MO 63110, USA


Abstract
The cingulo-opercular network (including the dorsal anterior cingulate and bilateral anterior insula) shows 3 distinct task-control signals across a wide variety of tasks, including trial-related signals that appear to come online at or near the end of the trial. Previous work suggests that there are separable responses in this network for errors and ambiguity, implicating multiple types of processing units within these regions. Using a unique paradigm, we directly show that these separable responses withhold activity to the end of the trial, in the service of reporting performance back into the task set. Participants performed a slow reveal task where images were presented behind a black mask which was gradually degraded, and they pressed a button when they could recognize the object that was being revealed. A behavioral pilot was used to identify ambiguous stimuli. We found interactive effects of accuracy and ambiguity, which suggests that these regions are computing and utilizing information, at one time, about both types of performance indices. Importantly, we showed a relationship between cingulo-opercular activity and behavioral performance, suggesting a role for these regions in performance reporting, per se. We discuss these results in the context of task control. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


Author Keywords
ambiguity;  error;  functional networks;  performance reporting;  task control


Document Type: Article
Source: Scopus

 

33) 

Church, J.A., Bunge, S.A., Petersen, S.E., Schlaggar, B.L.
Preparatory Engagement of Cognitive Control Networks Increases Late in Childhood
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (3), pp. 2139-2153. 

DOI: 10.1093/cercor/bhw046


a Department of Psychology, The University of Texas at Austin, Austin, TX 78712, USA
b Helen Wills Neuroscience Institute
c Department of Psychology, University of California at Berkeley, Berkeley, CA 94720, USA
d Department of Neurology
e Department of Radiology
f Department of Anatomy and Neurobiology
g Department of Neurosurgery
h Department of Psychology
i Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
j Department of Pediatrics
k Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA


Abstract
The ability to engage task control flexibly, especially in anticipation of task demands, is beneficial when juggling different tasks. We investigated whether children in late childhood or early adolescence engaged preparatory task control similar to adults in a trial-wise cued task-switching paradigm. Twenty-eight children (aged 9-15 years) and 30 adults (aged 21-30 years) participated in an fMRI study in which the Cue (preparatory) period across 2 tasks was analyzed separately from the execution of the tasks (the Target period). Children performed more slowly and less accurately than adults, and showed behavioral improvement within the child group age range of 9-15 years. Children exhibited weaker Cue period activation than adults within a number of putative cognitive control regions. In contrast, children exhibited greater activity than adults in several regions, including sensorimotor areas, during the Target period. Children who activated cognitive control-related regions more during the Cue period tended to activate the Target signal age-related regions less, and this correlated with improved accuracy and reaction time on the task, as well as age. The results endorse previous findings that preparatory cognitive control systems are still developing in late childhood, but add new evidence of age-related shifts in activity at the trial level. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


Author Keywords
adolescence;  development;  fMRI;  fronto-parietal;  task-switching


Document Type: Article
Source: Scopus

 

34) 

Athiraman, U., Rich, K.M.
CON: Deep brain stimulator insertion for functional neurosurgery under general anesthesia
(2017) Journal of Neurosurgical Anesthesiology, 29 (3), pp. 350-351. 

DOI: 10.1097/01.ana.0000520880.78588.8e


a Department of Anesthesiology, Washington University, St Louis, MO, United States
b Neurological Surgery, Washington University, School of Medicine, St Louis, MO, United States


Document Type: Short Survey
Source: Scopus

 

35) 

He, S., Teagle, H.F.B., Buchman, C.A.
The electrically evoked compound action potential: From laboratory to clinic
(2017) Frontiers in Neuroscience, 11 (JUN), art. no. 339, . 

DOI: 10.3389/fnins.2017.00339


a Center for Hearing Research, Boys Town National Research Hospital, Omaha, NE, United States
b Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
c Department of Otolaryngology-Head and Neck Surgery, Washington University, St. Louis, MO, United States


Abstract
The electrically evoked compound action potential (eCAP) represents the synchronous firing of a population of electrically stimulated auditory nerve fibers. It can be directly recorded on a surgically exposed nerve trunk in animals or from an intra-cochlear electrode of a cochlear implant. In the past two decades, the eCAP has been widely recorded in both animals and clinical patient populations using different testing paradigms. This paper provides an overview of recording methodologies and response characteristics of the eCAP, as well as its potential applications in research and clinical situations. Relevant studies are reviewed and implications for clinicians are discussed. © 2017 He, Teagle and Buchman.


Author Keywords
Auditory nerve;  Clinical application;  Cochlear implant outco;  Electrically evoked compound action potential;  Stimulating paradigm


Document Type: Review
Source: Scopus

 

36) 

Beharie, N., Jessell, L., Osuji, H., McKay, M.M.
The association between shelter rules and psychosocial outcomes among homeless youth residing in family shelters
(2017) Families in Society, 98 (2), pp. 113-120. 

DOI: 10.1606/1044-3894.2017.98.16


a New York University, Behavioral Science Training (BST) Program, NYU Rory Meyers College of Nursing, 10 Chesterwood Ave., Mount Vernon, NY, United States
b New York University, United States
c Brown School, Washington University, St. Louis, United States


Abstract
Despite growing numbers of homeless youth living in shelters with caregivers, little research has explored the impact of the shelter environment on emotional well-being. As such, this study assesses the relationship between shelter rules and two psychosocial outcomes among youth in New York City family shelters. Additionally, the direct effect of trauma and the moderating effect of difficulty following shelter rules on psychosocial outcomes was assessed. Youth with difficulty following shelter rules reported significantly more depressive symptoms, but less substance use. Trauma was found to be associated with increased depression and substance use. Difficulty following shelter rules was found to moderate the association between trauma and substance use. Recommendations for future interventions and the creation of shelter policies are discussed. © 2017 Alliance for Strong Families and Communities.


Document Type: Article
Source: Scopus



37) 

Salloum, N.C., Gott, B.M., Conway, C.R.
Sustained remission in patients with treatment-resistant depression receiving vagal nerve stimulation: A case series
(2017) Brain Stimulation, . Article in Press. 

DOI: 10.1016/j.brs.2017.06.001


Department of Psychiatry, Washington University in St. Louis, 660 S. Euclid Ave, Campus Box #8134, St. Louis, MO, USA


Author Keywords
Major depressive disorder;  Treatment-resistant depression;  Vagus nerve stimulation


Document Type: Article in Press
Source: Scopus

 

38) 

Sutter, E.N., Seidler, K.J., Duncan, R.P., Earhart, G.M., McNeely, M.E.
Low to moderate relationships between gait and postural responses in Parkinson's disease
(2017) Journal of Rehabilitation Medicine, 49 (6), pp. 505-511. 

DOI: 10.2340/16501977-2238


a Program in Physical Therapy, Washington University, School of Medicine in St. Louis, 4444 Forest Park Avenue, St. Louis, MO, United States
b Department of Neurology, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
c Department of Neuroscience, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States


Abstract
Objective: To evaluate the relationship between spatiotemporal parameters of forward and backward gait and quality of compensatory stepping responses in forward and backward directions in people with Parkinson's disease with and without freezing of gait. Design: Cross-sectional analysis. Subjects: A total of 111 individuals with mild to moderate Parkinson's disease. Methods: Forward and backward gait velocity and step length were evaluated using a GAITRite walkway. Forward and backward postural responses were evaluated using items from the Mini Balance Evaluation Systems Test and the Movement Disorders Society Unified Parkinson Disease Rating Scale motor subsection. Relationships between gait and postural responses were examined for the full sample and for sub-groups with and without freezing of gait. Results: There were significant (p < 0.05) low to moderate correlations between postural responses and gait overall. Correlations were similar in the freezer and non-freezer sub-groups. Freezers performed worse than non-freezers on all gait parameters and backward postural response items (p < 0.05). Conclusion: Low to moderate relationships between gait and postural responses indicate the complexity of postural control and the potential involvement of different neural circuitry across these tasks. Better understanding of the relationships between gait and postural deficits in Parkinson's disease may inform the future development of targeted interventions to address these impairments. © 2017 Foundation of Rehabilitation Information.


Author Keywords
Freezing of gait;  Gait;  Parkinson's disease;  Postural balance


Document Type: Article
Source: Scopus

 

39) 

Andelman, S.M., McAnany, S.J., Qureshi, S.A., Hecht, A.C.
Bilateral C5 motor palsy after anterior cervical decompression and fusion: A case report and review of the literature
(2017) International Journal of Spine Surgery, 11 (2), pp. 99-105. 

DOI: 10.14444/4014


a Mount Sinai Icahn School of Medicine, Department of Orthopaedic Surgery, Mount Sinai Hospital, New York, NY, United States
b Washington University, Department of Orthopaedic Surgery, St. Louis, MO, United States


Abstract
Background Bilateral C5 motor palsy is a rare but potentially debilitating complication after cervical spine decompression with very few reports in the published literature. Purpose To present a case of bilateral C5 motor palsy after anterior cervical decompression and fusion and discuss the incidence and risk factors of this complication. Study Design/Setting We report a case of a 57-year-old male who underwent a three level C3-C6 anterior cervical discectomy and fusion with instrumentation who developed a postoperative bilateral C5 motor palsy. Methods A review of the literature was performed regarding reports on and incidence of post-operative bilateral C5 palsy following either anterior or posterior cervical spine decompression. Results Bilateral C5 motor palsy is a rare complication of cervical spine decompression with an overall incidence of 0.38%. Although a group of risk factors have been suggested no single cause has been identified. Conclusions Bilateral C5 motor palsy is a rare but debilitating complication of cervical decompression.


Author Keywords
Bilateral;  C5 palsy;  Cervical decompression


Document Type: Article
Source: Scopus

 

40) 

Cole, M.W., Patrick, L.M., Meiran, N., Braver, T.S.
A role for proactive control in rapid instructed task learning
(2017) Acta Psychologica, . Article in Press. 

DOI: 10.1016/j.actpsy.2017.06.004


a Psychology Department, Washington University in St. Louis, MO 63130, United States
b Center for Molecular and Behavioral Neuroscience, Rutgers University, NJ 07102, United States
c Department of Psychology and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel


Abstract
Humans are often remarkably fast at learning novel tasks from instructions. Such rapid instructed task learning (RITL) likely depends upon the formation of new associations between long-term memory representations, which must then be actively maintained to enable successful task implementation. Consequently, we hypothesized that RITL relies more heavily on a proactive mode of cognitive control, in which goal-relevant information is actively maintained in preparation for anticipated high control demands. We tested this hypothesis using a recently developed cognitive paradigm consisting of 60 novel tasks involving RITL and 4 practiced tasks, with identical task rules and stimuli used across both task types. A robust behavioral cost was found in novel relative to practiced task performance, which was present even when the two were randomly inter-mixed, such that task-switching effects were equated. Novelty costs were most prominent under time-limited preparation conditions. In self-paced conditions, increased preparation time was found for novel trials, and was selectively associated with enhanced performance, suggesting greater proactive control for novel tasks. These results suggest a key role for proactive cognitive control in the ability to rapidly learn novel tasks from instructions. © 2017 Elsevier B.V.


Author Keywords
Cognitive control;  Proactive control;  Rapid instructed task learning


Document Type: Article in Press
Source: Scopus

 

41) 

Zhang, P., Li, L., Lin, L., Hu, P., Shi, J., He, Y., Zhu, L., Zhou, Y., Wang, L.V.
High-resolution deep functional imaging of the whole mouse brain by photoacoustic computed tomography invivo
(2017) Journal of Biophotonics, . Article in Press. 

DOI: 10.1002/jbio.201700024


a Optical Imaging Laboratory, Department of Biomedical Engineering Washington University in St. Louis St. Louis, Missouri 63130 USA
b Department of Medical Engineering California Institute of Technology 1200 E California Blvd. Pasadena, CA 91125
c Department of Electrical Engineering California Institute of Technology 1200 E California Blvd., Pasadena, CA 91125


Abstract
Photoacoustic computed tomography (PACT) is a non-invasive imaging technique offering high contrast, high resolution, and deep penetration in biological tissues. We report a PACT system equipped with a high frequency linear transducer array for mapping the microvascular network of a whole mouse brain with the skull intact and studying its hemodynamic activities. The linear array was scanned in the coronal plane to collect data from different angles, and full-view images were synthesized from the limited-view images in which vessels were only partially revealed. We investigated spontaneous neural activities in the deep brain by monitoring the concentration of hemoglobin in the blood vessels and observed strong interhemispherical correlations between several chosen functional regions, both in the cortical layer and in the deep regions. We also studied neural activities during an epileptic seizure and observed the epileptic wave spreading around the injection site and the wave propagating in the opposite hemisphere. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Author Keywords
Deep mouse brain;  Functional imaging;  Photoacoustic computed tomography


Document Type: Article in Press
Source: Scopus

 

42) 

Zero, V.H., Barocas, A., Jochimsen, D.M., Pelletier, A., Giroux-Bougard, X., Trumbo, D.R., Castillo, J.A., Mack, D.E., Linnell, M.A., Pigg, R.M., Hoisington-Lopez, J., Spear, S.F., Murphy, M.A., Waits, L.P.
Complementary network-based approaches for exploring genetic structure and functional connectivity in two vulnerable, endemic ground squirrels
(2017) Frontiers in Genetics, 8 (JUN), art. no. 81, . 

DOI: 10.3389/fgene.2017.00081


a Haub School of Environment and Natural Resources, University of Wyoming, Laramie, WY, United States
b Department of Zoology and Physiology, University of Wyoming, Laramie, WY, United States
c University of Wyoming, Laramie, WY, United States
d Department of Biological Sciences, University of Idaho, Moscow, ID, United States
e Department of Environmental Studies and Sciences, University of Winnipeg, Winnipeg, MB, Canada
f Department of Natural Resource Sciences, McGill University, Montreal, QC, Canada
g School of Biological Sciences, Washington State University, Pullman, WA, United States
h Department of Fisheries and Wildlife, Oregon State University, Corvallis, OR, United States
i Idaho Department of Fish and Game, McCall Subregion, McCall, ID, United States
j Division of Biology, Kansas State University, Manhattan, KS, United States
k The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, United States
l The Wilds, Cumberland, OH, United States
m Department of Ecosystem Science and Management, University of Wyoming, Laramie, WY, United States
n Department of Fish and Wildlife Sciences, University of Idaho, Moscow, ID, United States


Abstract
The persistence of small populations is influenced by genetic structure and functional connectivity. We used two network-based approaches to understand the persistence of the northern Idaho ground squirrel (Urocitellus brunneus) and the southern Idaho ground squirrel (U. endemicus), two congeners of conservation concern. These graph theoretic approaches are conventionally applied to social or transportation networks, but here are used to study population persistence and connectivity. Population graph analyses revealed that local extinction rapidly reduced connectivity for the southern species, while connectivity for the northern species could be maintained following local extinction. Results from gravity models complemented those of population graph analyses, and indicated that potential vegetation productivity and topography drove connectivity in the northern species. For the southern species, development (roads) and small-scale topography reduced connectivity, while greater potential vegetation productivity increased connectivity. Taken together, the results of the two network-based methods (population graph analyses and gravity models) suggest the need for increased conservation action for the southern species, and that management efforts have been effective at maintaining habitat quality throughout the current range of the northern species. To prevent further declines, we encourage the continuation of management efforts for the northern species, whereas conservation of the southern species requires active management and additional measures to curtail habitat fragmentation. Our combination of population graph analyses and gravity models can inform conservation strategies of other species exhibiting patchy distributions. © 2017 Zero, Barocas, Jochimsen, Pelletier, Giroux-Bougard, Trumbo, Castillo, Evans Mack, Linnell, Pigg, Hoisington-Lopez, Spear, Murphy and Waits.


Author Keywords
Functional connectivity;  Gene flow;  Graph theory;  Gravity model;  Landscape genetics;  Sciuridae;  Urocitellus [Spermophilus]


Document Type: Article
Source: Scopus

 

43) 

Bove, R., Elsone, L., Alvarez, E., Borisow, N., Cortez, M.M., Mateen, F.J., Mealy, M.A., Mutch, K., Tobyne, S., Ruprecht, K., Buckle, G., Levy, M., Wingerchuk, D.M., Paul, F., Cross, A.H., Weinshenker, B., Jacob, A., Klawiter, E.C., Chitnis, T.
Female hormonal exposures and neuromyelitis optica symptom onset in a multicenter study
(2017) Neurology: Neuroimmunology and NeuroInflammation, 4 (3), art. no. e339, . 

DOI: 10.1212/NXI.0000000000000339


a Brigham and Women's Hospital, Boston, MA, United States
b Harvard Medical School, Boston, MA, United States
c Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
d Washington University, School of Medicine, St. Louis, MO, United States
e Charité-Universitätsmedizin Berlin, Germany
f University of Utah, Imaging and Neurosciences Center, Salt Lake City, United States
g Massachusetts General Hospital, Boston, United States
h Johns Hopkins Medical Institute, Baltimore, MD, United States
i MS Institute, Shepherd Center, Atlanta, GA, United States
j Mayo Clinic, Rochester, MN, United States
k Mayo Clinic, Scottsdale, AZ, United States


Abstract
Objective: To study the association between hormonal exposures and disease onset in a cohort of women with neuromyelitis optica spectrum disorder (NMOSD). Methods: Reproductive history and hormone use were assessed using a standardized reproductivesurveyadministered towomen with NMOSD (82% aquaporin-4antibody positive) at 8clinical centers. Using multivariable regression, we examined the association between reproductive exposures and age at first symptom onset (FS). Results: Among 217 respondents, the mean age at menarche was 12.8 years (SD 1.7). The mean number of pregnancies was 2.1 (SD 1.6), including 0.3 (SD 0.7) occurring after onset of NMOSD symptoms. In the 117 participants who were postmenopausal at the time of the questionnaire, 70% reported natural menopause (mean age: 48.9 years [SD 3.9]); fewer than 30% reported systemic hormone therapy (HT) use. Mean FS age was 40.1 years (SD 14.2). Ever-use of systemic hormonal contraceptives (HC) was marginally associated with earlier FS (39 vs 43 years, p 5 0.05). Because HC use may decrease parity, when we included both variables in the model, the association between HC use and FS age became more significant (estimate 5 2.7, p 5 0.007). Among postmenopausal participants, 24% reported NMOSD onset within 2 years of (before or after) menopause. Among these participants, there was no association between age at menopause or HT use and age at NMOSD onset. Conclusions: Overall, age at NMOSD onset did not show a strong relationship with endogenous hormonal exposures. An earlier onset age did appear to be marginally associated with systemic HC exposure, an association that requires confirmation in future studies. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.


Document Type: Article
Source: Scopus

 

44) 

Tempelhoff, R.
General versus local anesthesia for deep brain stimulator insertion
(2017) Journal of Neurosurgical Anesthesiology, 29 (3), p. 347. 

DOI: 10.1097/ANA.0000000000000394


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


Document Type: Note
Source: Scopus

 

45) 

Hajirezaei, S., Mohammadi, A., Soleimani, M., Rahiminezhad, F., Mohammadi, M.R., Cloninger, C.R.
Comparing the profile of temperament and character dimensions in patients with major depressive disorder and bipolar mood disorder with a control group
(2017) Iranian Journal of Psychiatry, 12 (3), pp. 147-153. 


a Department of Psychiatry, Tehran University of Medical Sciences, Tehran, Iran
b Psychiatric and Psychology Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
c Center for Psychobiology of Personality, Sansone Center for Well-Being, Washington University St Louis, St Louis, MO, United States


Abstract
Objective: This study was conducted to compare the profile of temperament and character dimensions in patients with major depressive disorder and bipolar mood disorder with a control group. Method: In this causal-comparative study, the population consisted of 2 clinical groups (major depressive disorder and bipolar mood disorder) and a non-clinical group. The sample was 193 individuals (77 patients with major depressive disorder, 86 patients with bipolar mood disorder, and 30 controls), with an age range of 18 to 65 years and the mean age of 40.1. They were selected from Roozbeh psychiatric hospital using available sampling method. Tools used in this research included Temperament and Character Inventory-140 and General Health Questionnaire-28. Collected data were analyzed by independent t test and one-way analysis of variance using Statistical Package for the Social Sciences-22 software. Results: The results revealed a significant difference among groups in dimensions of novelty seeking, harm avoidance, persistence, self-directedness, and cooperativeness (P < 0.05). The results showed that the mean was different in males and females only in the novelty seeking dimension (P < 0.05). Conclusion: In general, our results revealed that patients with major depressive disorder and bipolar mood disorder have different personality profiles in some dimensions of temperament and character compared with the control group.


Author Keywords
Bipolar mood disorder;  Control group;  Major depressive disorder;  Personality profile;  Temperament and character inventory


Document Type: Article
Source: Scopus

 

46) 

Commean, P.K., Smith, K.E., Hildebolt, C.F., Bohnert, K.L., Sinacore, D.R., Prior, F.W.
A Candidate Imaging Marker for Early Detection of Charcot Neuroarthropathy
(2017) Journal of Clinical Densitometry, . Article in Press. 

DOI: 10.1016/j.jocd.2017.05.008


a Electronic Radiology Laboratory, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
b Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
c Applied Kinesiology Laboratory, Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO, USA


Abstract
Inflammation-mediated foot osteopenia may play a pivotal role in the etiogenesis, pathogenesis, and therapeutic outcomes in individuals with diabetes mellitus (DM), peripheral neuropathy (PN), and Charcot neuroarthropathy (CN). Our objective was to establish a volumetric quantitative computed tomography-derived foot bone measurement as a candidate prognostic imaging marker to identify individuals with DMPN who were at risk of developing CN. We studied 3 groups: 16 young controls (27 ± 5 years), 20 with DMPN (57 ± 11 years), and 20 with DMPN and CN (55 ± 9 years). Computed tomography image analysis was used to measure metatarsal and tarsal bone mineral density in both feet. The mean of 12 right (7 tarsals and 5 metatarsals) and 12 left foot bone mineral densities, maximum percent difference in bone mineral density between paired bones of the right and the left feet, and the mean difference of the 12 right and the 12 left bone mineral density measurements were used as input variables in different classification analysis methods to determine the best classifier. Classification tree analysis produced no misclassification of the young controls and individuals with DMPN and CN. The tree classifier found 7 of 20 (35%) individuals with DMPN to be classified as CN (1 participant developed CN during follow-up) and 13 (65%) to be classified as healthy. These results indicate that a decision tree employing 3 measurements derived from volumetric quantitative computed tomography foot bone mineral density defines a candidate prognostic imaging marker to identify individuals with diabetes and PN who are at risk of developing CN. © 2017 The International Society for Clinical Densitometry.


Author Keywords
Candidate imaging marker;  Charcot neuroarthropathy;  Diabetes mellitus;  Foot bone mineral density;  Peripheral neuropathy


Document Type: Article in Press
Source: Scopus

 

47) 

Gilmore, A.W., Nelson, S.M., Chen, H.-Y., McDermott, K.B.
Task-related and resting-state fMRI identify distinct networks that preferentially support remembering the past and imagining the future
(2016) Neuropsychologia, . Article in Press. 

DOI: 10.1016/j.neuropsychologia.2017.06.016


a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA
b Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA
c VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX 76711, USA
d Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX 75235, USA
e Department of Psychology and Neuroscience, Baylor University, Waco, TX 76789, USA


Abstract
The relation between episodic memory and episodic future thought (EFT) remains an active target of research. A growing literature suggests that similar cognitive processes and neural substrates tend to support these acts. However, direct comparisons of whole-brain activity reveal clear differences, with numerous regions more active when engaging in EFT than when remembering, and a smaller collection of regions displaying the opposite pattern of activity. Although various network labels have been applied to prior neuroimaging results, to date no formal resting-state functional connectivity analysis has been conducted. In the current experiment, 48 subjects remembered events from their past and engaged in EFT. Resting-state data were collected from all subjects. Task results replicated recent findings, with more activity during EFT in regions across frontal and parietal cortex, and with more activity during remembering in a smaller number of predominantly parahippocampal and retrosplenial regions. Resting-state connectivity analysis, based on seed locations defined using the fMRI task data, indicated that regions preferentially activated during EFT fell primarily within the default mode network, while those more active during remembering fell primarily within the contextual association network. These results suggest that despite their general similarity, the functional network membership of regions showing task differences is dissociable. We discuss our results in light of several hypotheses that attempt to relate remembering and EFT, and suggest that the data speak to differences in the relative contributions of episodic and semantic memory, as well as controlled and automatic processing, during the acts of remembering or engaging in EFT. © 2017.


Author Keywords
Contextual association network;  Default mode network;  Episodic future thought;  Episodic memory;  Resting-state functional connectivity


Document Type: Article in Press
Source: Scopus

 

48) 

Santibáñez-Briones, V., García-Santibáñez, R.
Clinical reasoning: 57 year-old male with pain and proximal muscle weakness [Razonamiento Clínico: Hombre de 57 Años de Edad con Dolor y Debilidad Muscular Proximal]
(2016) Revista Ecuatoriana de Neurologia, 25 (1-3), pp. 76-79. 


a Departamento de Medicina Interna, Icahn School of Medicine at Mount Sinai, Mount Sinai, United States
b Departamento de Medicina Neuromuscular, Washington University, St. Louis, United States


Abstract
We present a case of a 57-year-old man with a two-month history of shoulder pain and proximal weakness. The history and physical examination are reviewed and a stepwise approach to the differential diagnosis is made to reach the final diagnosis. Keywords: differential diagnosis, proximal weakness, diabetes mellitus.


Document Type: Article
Source: Scopus

 

49) 

Aguirre-Fernández, D., Garcia-Santibanez, R.
Sporadic inclusion body myositis [Miositis Esporádica por Cuerpos de Inclusión]
(2016) Revista Ecuatoriana de Neurologia, 25 (1-3), pp. 44-49. 


a Médico, Universidad Católica de Santiago de Guayaquil, Ecuador
b Departamento de Neurología, Washington University, St. Louis, United States


Abstract
Sporadic inclusion body myositis is a common acquired inflammatory myopathy in people over 50 years of age. It presents with slowly progressive asymmetric weakness that affects preferentially the quadriceps and deep finger flexors. The pathogenesis is poorly understood. The diagnosis is made with a combination of the clinical history, physical exam, electrodiagnostic tests, imaging, serology and histopathology. There is no treatment for this condition but multiple therapies are currently being investigated.


Author Keywords
Inclusion bodies;  Inflammation;  Myopathy;  Pathogenesis;  Pathology


Document Type: Review
Source: Scopus

July 3, 2017 

1) 

Fontenot, T.E., Giardina, C.K., Teagle, H.F., Park, L.R., Adunka, O.F., Buchman, C.A., Brown, K.D., Fitzpatrick, D.C.
Clinical role of electrocochleography in children with auditory neuropathy spectrum disorder
(2017) International Journal of Pediatric Otorhinolaryngology, 99, pp. 120-127. 

DOI: 10.1016/j.ijporl.2017.05.026


a University of North Carolina at Chapel Hill, Department of Otolaryngology, Chapel Hill, NC, United States
b University of North Carolina School of Medicine, Chapel Hill, NC, United States
c The Ohio State University, Department of Otolaryngology, Columbus, OH, United States
d Washington University in St. Louis, Department of Otolaryngology, St. Louis, MO, United States


Abstract
Objectives To assess electrocochleography (ECochG) to tones as an instrument to account for CI speech perception outcomes in children with auditory neuropathy spectrum disorder (ANSD). Materials & methods Children (<18 years) receiving CIs for ANSD (n = 30) and non-ANSD (n = 74) etiologies of hearing loss were evaluated with ECochG using tone bursts (0.25–4 kHz). The total response (TR) is the sum of spectral peaks of responses across frequencies. The compound action potential (CAP) and the auditory nerve neurophonic (ANN) in ECochG waveforms were used to estimate nerve activity and calculate nerve score. Performance on open-set monosyllabic word tests was the outcome measure. Standard statistical methods were applied. Results On average, TR was larger in ANSD than in non-ANSD subjects. Most ANSD (73.3%) and non-ANSD (87.8%) subjects achieved open-set speech perception; TR accounted for 33% and 20% of variability in the outcomes, respectively. In the ANSD group, the PTA accounted for 69.3% of the variability, but there was no relationship with outcomes in the non-ANSD group. In both populations, nerve score was sensitive in identifying subjects at risk for not acquiring open-set speech perception, while the CAP and the ANN were more specific. Conclusion In both subject groups, the TRs correlated with outcomes but these measures were notably larger in the ANSD group. There was also strong correlation between PTA and speech perception outcome in ANSD group. In both subject populations, weaker evidence of neural activity was related to failure to achieve open-set speech perception. © 2017 Elsevier B.V.


Author Keywords
Auditory nerve neurophonic;  Auditory neuropathy spectrum disorder;  Cochlear implants;  Compound action potential;  Electrocochleography


Document Type: Article
Source: Scopus

 

2) 

Barch, D.M.
Biotypes: Promise and Pitfalls
(2017) Biological Psychiatry, 82 (1), pp. 2-3. 

DOI: 10.1016/j.biopsych.2017.04.012


a Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri, United States
c Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, United States


Document Type: Note
Source: Scopus

 

3) 

Trivedi, S.B., Vesoulis, Z.A., Rao, R., Liao, S.M., Shimony, J.S., McKinstry, R.C., Mathur, A.M.
A validated clinical MRI injury scoring system in neonatal hypoxic-ischemic encephalopathy
(2017) Pediatric Radiology, pp. 1-9. Article in Press. 

DOI: 10.1007/s00247-017-3893-y


a Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics,, Washington University School of Medicine, One Children’s Place, Campus Box 8116,, St. Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Background: Deep nuclear gray matter injury in neonatal hypoxic-ischemic encephalopathy (HIE) is associated with worse neurodevelopmental outcomes. We previously published a qualitative MRI injury scoring system utilizing serial T1-weighted, T2-weighted and diffusion-weighted imaging (DWI), weighted for deep nuclear gray matter injury. Objectives: To establish the validity of the MRI scoring system with neurodevelopmental outcome at 18-24 months. Materials and methods: MRI scans from neonates with moderate to severe HIE treated with therapeutic hypothermia were evaluated. Signal abnormality was scored on T1-weighted, T2-weighted and DWI sequences and assessed using an established system in five regions: (a) subcortical: caudate nucleus, globus pallidus and putamen, thalamus and the posterior limb of the internal capsule; (b) white matter; (c) cortex, (d) cerebellum and (e) brainstem. MRI injury was graded as none, mild, moderate or severe. Inter-rater reliability was tested on a subset of scans by two independent and blinded neuroradiologists. Surviving infants underwent the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18-24 months. Data were analyzed using univariate and multivariate linear and logistic regression. Results: Fifty-seven eligible neonates underwent at least one MRI scan in the first 2 weeks of life. Mean postnatal age at scan 1 was 4±2 days in 50/57 (88%) neonates and 48/54 (89%) surviving infants underwent scan 2 at 10±2 days. In 54/57 (95%) survivors, higher MRI injury grades were significantly associated with worse outcomes in the cognitive, motor and language domains of the Bayley-III. Conclusion: A qualitative MRI injury scoring system weighted for deep nuclear gray matter injury is a significant predictor of neurodevelopmental outcome at 18–24 months in neonates with HIE. © 2017 Springer-Verlag Berlin Heidelberg


Author Keywords
Brain;  Hypoxic-ischemic encephalopathy;  Magnetic resonance imaging;  Neonates;  Neurodevelopmental outcome;  Scoring system


Document Type: Article in Press
Source: Scopus

 

4) 

Frieden, C., Wang, H., Ho, C.M.W.
A mechanism for lipid binding to apoE and the role of intrinsically disordered regions coupled to domain-domain interactions
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (24), pp. 6292-6297. 

DOI: 10.1073/pnas.1705080114


a Department of Biochemistry and Molecular Biophysics, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Chemistry, Washington University in St. Louis, St. Louis, MO, United States
c Drug Design Methodologies LLC, St. Louis, MO, United States
d Analytical Research and Development, Pfizer Inc., Chesterfield, MO, United States


Abstract
Relative to the apolipoprotein E (apoE) E3 allele of the APOE gene, apoE4 strongly increases the risk for the development of late-onset Alzheimer's disease. However, apoE4 differs from apoE3 by only a single amino acid at position 112, which is arginine in apoE4 and cysteine in apoE3. It remains unclear why apoE3 and apoE4 are functionally different. Described here is a proposal for understanding the functional differences between these two isoforms with respect to lipid binding. A mechanism is proposed that is based on the full-length monomeric structure of the protein, on hydrogen-deuterium exchange mass spectrometry data, and on the role of intrinsically disordered regions to control protein motions. It is proposed that lipid binds between the N-terminal and C-terminal domains and that separation of the two domains, along with the presence of intrinsically disordered regions, controls this process. The mechanism explains why apoE3 differs from apoE4 with respect to different lipid-binding specificities, why lipid increases the binding of apoE to its receptor, and why specific residues are conserved.


Author Keywords
Apolipoprotein E;  Conserved residues;  Domain-domain interaction;  Hydrogen-deuterium exchange;  Protein structure


Document Type: Article
Source: Scopus

 

5) 

Cavalli, F.M.G., Remke, M., Rampasek, L., Peacock, J., Shih, D.J.H., Luu, B., Garzia, L., Torchia, J., Nor, C., Morrissy, A.S., Agnihotri, S., Thompson, Y.Y., Kuzan-Fischer, C.M., Farooq, H., Isaev, K., Daniels, C., Cho, B.-K., Kim, S.-K., Wang, K.-C., Lee, J.Y., Grajkowska, W.A., Perek-Polnik, M., Vasiljevic, A., Faure-Conter, C., Jouvet, A., Giannini, C., Nageswara Rao, A.A., Li, K.K.W., Ng, H.-K., Eberhart, C.G., Pollack, I.F., Hamilton, R.L., Gillespie, G.Y., Olson, J.M., Leary, S., Weiss, W.A., Lach, B., Chambless, L.B., Thompson, R.C., Cooper, M.K., Vibhakar, R., Hauser, P., van Veelen, M.-L.C., Kros, J.M., French, P.J., Ra, Y.S., Kumabe, T., López-Aguilar, E., Zitterbart, K., Sterba, J., Finocchiaro, G., Massimino, M., Van Meir, E.G., Osuka, S., Shofuda, T., Klekner, A., Zollo, M., Leonard, J.R., Rubin, J.B., Jabado, N., Albrecht, S., Mora, J., Van Meter, T.E., Jung, S., Moore, A.S., Hallahan, A.R., Chan, J.A., Tirapelli, D.P.C., Carlotti, C.G., Fouladi, M., Pimentel, J., Faria, C.C., Saad, A.G., Massimi, L., Liau, L.M., Wheeler, H., Nakamura, H., Elbabaa, S.K., Perezpeña-Diazconti, M., Chico Ponce de León, F., Robinson, S., Zapotocky, M., Lassaletta, A., Huang, A., Hawkins, C.E., Tabori, U., Bouffet, E., Bartels, U., Dirks, P.B., Rutka, J.T., Bader, G.D., Reimand, J., Goldenberg, A., Ramaswamy, V., Taylor, M.D.
Intertumoral Heterogeneity within Medulloblastoma Subgroups
(2017) Cancer Cell, 31 (6), pp. 737-754.e6. Cited 1 time.

DOI: 10.1016/j.ccell.2017.05.005


a The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada
b Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada
c Department of Pediatric Oncology, Hematology, Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany
d Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
e Department of Computer Science, University of Toronto, Toronto, ON, Canada
f Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
g UPCI Brain Tumor Program, University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, PA, United States
h Informatics Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
i Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
j Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, South Korea
k Department of Pathology, The Children's Memorial Health Institute, University of Warsaw, Warsaw, Poland
l Department of Oncology, The Children's Memorial Health Institute, University of Warsaw, Warsaw, Poland
m Centre de Pathologie et Neuropathologie Est, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France
n Institute of Pediatric Hematology and Oncology, Lyon, France
o Centre de Pathologie EST, Groupement Hospitalier EST, Université de Lyon, Bron, France
p Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States
q Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, MN, United States
r Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, Hong Kong
s Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, MD, United States
t Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
u Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
v Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, United States
w Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
x Division of Pediatric Hematology/Oncology, University of Washington School of Medicine, Seattle Children's Hospital, Seattle, WA, United States
y Departments of Pediatrics, Neurological Surgery and Neurology, University of California San Francisco, San Francisco, CA, United States
z Division of Anatomical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
aa Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, United States
ab Department of Neurology, Vanderbilt Medical Center, Nashville, TN, United States
ac Department of Pediatrics, University of Colorado Denver, Aurora, CO, United States
ad 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
ae Department of Neurosurgery, Erasmus University Medical Center, Rotterdam, CE, Netherlands
af Department of Pathology, Erasmus University Medical Center, Rotterdam, CN, Netherlands
ag Department of Neurology, Erasmus University Medical Center, Rotterdam, CE, Netherlands
ah Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul, South Korea
ai Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
aj Division of Pediatric Hematology/Oncology, Hospital Pediatría Centro Médico Nacional Century XXI, Mexico City, Mexico
ak Department of Pediatric Oncology, School of Medicine, Masaryk University, Brno, Czech Republic
al Department of Neuro-Oncology, Istituto Neurologico Besta, Milan, Italy
am Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
an Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, United States
ao Division of Stem Cell Research, Institute for Clinical Research, Osaka National Hospital, Osaka, Japan
ap Department of Neurosurgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary
aq Dipartimento di Biochimica e Biotecnologie Mediche, University of Naples, Naples, Italy
ar Division of Pediatric Neurosurgery, Department of Neurosurgery, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, United States
as Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, United States
at Division of Hematology/Oncology, Department of Pediatrics, McGill University, Montreal, QC, Canada
au Department of Pathology, McGill University, Montreal, QC, Canada
av Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
aw Department of Pediatrics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States
ax Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam, South Korea
ay Lady Cilento Children's Hospital, The University of Queensland, Brisbane, QLD, Australia
az Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada
ba Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
bb Division of Hematology/Oncology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
bc Divison of Pathology, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal
bd Division of Neurosurgery, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal
be Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States
bf Department of Pediatric Neurosurgery, Catholic University Medical School, Rome, Italy
bg Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
bh Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia
bi Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, Kumamoto, Japan
bj Division of Pediatric Neurosurgery, Department of Neurosurgery, Saint Louis University School of Medicine, St. Louis, MO, United States
bk Department of Pathology, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico
bl Department of Neurosurgery, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico
bm Division of Pediatric Neurosurgery, Rainbow & Babies Children's Hospital, Case Western Reserve, Cleveland, OH, United States
bn Division of Haematology / Oncology, The Hospital for Sick Children, Toronto, ON, Canada
bo Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada
bp Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada
bq The Donnelly Centre, University of Toronto, Toronto, ON, Canada
br Program in Neuroscience and Mental Health and Division of Neurology, The Hospital for Sick Children, Toronto, ON, Canada
bs Department of Pediatric Neuro-Oncogenomics, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Düsseldorf, Germany
bt ONCOFLAM - Neuro-Oncologie et Neuro-Inflammation Centre de Recherche en Neurosciences de Lyon, Lyon, France
bu Department of Pathology and Laboratory Medicine, Hamilton General Hospital, Hamilton, ON, Canada
bv Department of Pathology, Montreal Children's Hospital, Montreal, QC, Canada
bw Oncology Service, Children's Health Queensland Hospital and Health Service, South Brisbane, QLD, Australia
bx Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada
by McLaughlin Centre, University of Toronto, Toronto, ON, Canada
bz Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
ca Samuel Lunenfeld Research Institute at Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada


Abstract
While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. © 2017 Elsevier Inc.


Author Keywords
copy number;  gene expression;  integrative clustering;  medulloblastoma;  methylation;  subgroups


Document Type: Article
Source: Scopus

 

6) 

Ball, B.H., Aschenbrenner, A.J.
The importance of age-related differences in prospective memory: Evidence from diffusion model analyses
(2017) Psychonomic Bulletin and Review, pp. 1-9. Article in Press. 

DOI: 10.3758/s13423-017-1318-4


a Department of Psychology, Washington University in Saint Louis, CB 1125, 1 Brookings Drive, St. Louis, MO, United States
b Department of Neurology, Washington University in Saint Louis, St Louis, MO, United States


Abstract
Event-based prospective memory (PM) refers to relying on environmental cues to trigger retrieval of a deferred action plan from long-term memory. Considerable research has demonstrated PM declines with increased age. Despite efforts to better characterize the attentional processes that underlie these decrements, the majority of research has relied on measures of central tendency to inform theoretical accounts of PM that may not entirely capture the underlying dynamics involved in allocating attention to intention-relevant information. The purpose of the current study was to examine the utility of the diffusion model to better understand the cognitive processes underlying age-related differences in PM. Results showed that emphasizing the importance of the PM intention increased cue detection selectively for older adults. Standard cost analyses revealed that PM importance increased mean response times and accuracy, but not differentially for young and older adults. Consistent with this finding, diffusion model analyses demonstrated that PM importance increased response caution as evidenced by increased boundary separation. However, the selective benefit in cue detection for older adults may reflect peripheral target-checking processes as indicated by changes in nondecision time. These findings highlight the use of modeling techniques to better characterize the processes underlying the relations among aging, attention, and PM. © 2017 Psychonomic Society, Inc.


Author Keywords
Aging;  Attention;  Diffusion model;  Older adults;  Prospective memory


Document Type: Article in Press
Source: Scopus

 

7) 

Kung, N.H., Van Stavern, G.P., Bucelli, R.C.
A middle-aged man with progressive ophthalmoparesis, ataxia, and spastic paraparesis
(2017) JAMA Neurology, 74 (6), pp. 733-736. 

DOI: 10.1001/jamaneurol.2017.0055


a Department of Ophthalmology, Washington University in St. Louis, St Louis, MO, United States
b Department of Neurology, Washington University in St. Louis, St Louis, MO, United States


Abstract
A 50-year old man presented for evaluation of progressive gait ataxia with a superimposed spastic paraparesis. During his clinic visit, he was also observed to have slow and limited eye movements. In this article, we discuss the clinical approach to this triad of symptoms and guide the reader to discover the patient's ultimate genetic diagnosis. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

8) 

Sheffield, J.M., Kandala, S., Tamminga, C.A., Pearlson, G.D., Keshavan, M.S., Sweeney, J.A., Clementz, B.A., Lerman-Sinkoff, D.B., Hill, S.K., Barch, D.M.
Transdiagnostic associations between functional brain network integrity and cognition
(2017) JAMA Psychiatry, 74 (6), pp. 605-613. 

DOI: 10.1001/jamapsychiatry.2017.0669


a Department of Psychological and Brain Sciences, Washington University, One Brookings Drive, St Louis, MO, United States
b Department of Psychiatry, Washington University, School of Medicine, St Louis, MO, United States
c Department of Psychiatry and Pediatrics, University of Texas Southwestern Medical Center, Dallas, United States
d Departments of Psychiatry and Neurobiology, Yale University, New Haven, CT, United States
e Olin Research Center, Institute of Living, Hartford, CT, United States
f Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, United States
g Department of Psychiatry, Harvard Medical School, Boston, MA, United States
h Department of Psychiatry, University of Cincinnati, Cincinnati, OH, United States
i BioImaging Research Center, Department of Psychology, University of Georgia, Athens, United States
j BioImaging Research Center, Department of Neuroscience, University of Georgia, Athens, United States
k Department of Biomedical Engineering, Washington University, St Louis, MO, United States
l Department of Psychology, Rosalind Franklin University of Medicine and Science, Chicago, IL, United States
m Department of Radiology, Washington University, School of Medicine, St Louis, MO, United States


Abstract
IMPORTANCE Cognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs. OBJECTIVE To examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains. DESIGN, SETTING, AND PARTICIPANTS A total of 201 healthy control participants and 375 patients with psychotic disorders from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were studied from September 29, 2007, to May 31, 2011. The B-SNIP recruited healthy controls and stable outpatients from 6 sites: Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Detroit, Michigan; and Hartford, Connecticut. All participants underwent cognitive testing and resting-state functional magnetic resonance imaging. Data analysis was performed from April 28, 2015, to February 21, 2017. MAIN OUTCOMES AND MEASURES The Brief Assessment of Cognition in Schizophreniawas used to measure cognitive ability. A principal axis factor analysis on the Brief Assessment of Cognition in Schizophrenia battery yielded a single factor (54%variance explained) that served as the measure of general cognitive ability. Functional network integrity measures included global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network, and auditory network and exploratory analyses of all networks from the Power atlas. Group differences in network measures, associations between cognition and network measures, and mediation models were tested. RESULTS The final sample for the current study included 201 healthy controls, 143 patients with schizophrenia, 103 patients with schizoaffective disorder, and 129 patients with psychotic bipolar disorder (mean [SD] age, 35.1 [12.0] years; 281 male [48.8%] and 295 female [51.2%]; 181 white [31.4%], 348 black [60.4%], and 47 other [8.2%]). Patients with schizophrenia (Cohen d = 0.36, P &lt; .001) and psychotic bipolar disorder (Cohen d = 0.33, P = .002) had significantly reduced CON global efficiency compared with healthy controls. All patients with psychotic disorders had significantly reduced CON local efficiency, but the clinical groups did not differ from one another. The CON global efficiency was significantly associated with general cognitive ability across all groups (β = 0.099, P = .009) and significantly mediated the association between psychotic disorder status and general cognition (β =-0.037; 95%CI, .0.076 to .0.014). Subcortical network global efficiency was also significantly reduced in psychotic disorders (F3,587 = 4.01, P = .008) and positively predicted cognitive ability (β = 0.094, P = .009). CONCLUSIONS AND RELEVANCE These findings provide evidence that reduced CON and subcortical network efficiency play a role in the general cognitive deficit observed across the psychosis spectrum. They provide new support for the dimensional hypothesis that a shared neurobiological mechanism underlies cognitive impairment in psychotic disorders. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

9) 

Stephens, R.J., Dettmer, M.R., Roberts, B.W., Fowler, S.A., Fuller, B.M.
Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: A systematic review protocol
(2017) BMJ Open, 7 (6), art. no. e016437, . 

DOI: 10.1136/bmjopen-2017-016437


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


Abstract
Introduction: Mechanical ventilation is a commonly performed intervention in critically ill patients. Frequently, these patients experience deep sedation early in their clinical course. Emerging data suggest that the practice of early deep sedation may negatively impact patient outcomes. The purpose of this review is to assess the world's literature to describe and determine the impact of early deep sedation on the outcomes of mechanically ventilated patients. Methods and analysis: Randomised controlled trials and non-randomised studies will be eligible for inclusion in this systematic review. With the assistance of a medical librarian, we will comprehensively search MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, and Cochrane Database of Systematic Reviews for peer-reviewed literature. Grey literature from appropriate professional society conferences, held from 2010 to 2017, will be reviewed manually. Two authors will independently review all search results, and disagreements will be resolved through arbitration by a third author. If appropriate, meta-analysis will be used for quantitative analysis of the data. Heterogeneity between studies will be assessed using the I 2 statistic. Ethics and dissemination: The proposed systematic review will not collect data that are associated with individual patients and does not require ethical approval. Results of this study will contribute to the understanding of early sedation, identify future research targets and guide early care in mechanically ventilated patients. © 2017 Article author(s).


Author Keywords
mechanical ventilation;  meta-analysis;  sedation;  systematic review


Document Type: Review
Source: Scopus

 

10) 

Grucza, R.A.
Changing Demographics of Marijuana Initiation: Bad News or Good?
(2017) American Journal of Public Health, 107 (6), pp. 833-834. 

DOI: 10.2105/AJPH.2017.303804


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


Document Type: Editorial
Source: Scopus

 

11) 

Guilherme, A., Pedersen, D.J., Henchey, E., Henriques, F.S., Danai, L.V., Shen, Y., Yenilmez, B., Jung, D., Kim, J.K., Lodhi, I.J., Semenkovich, C.F., Czech, M.P.
Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming
(2017) Molecular Metabolism, . Article in Press. 

DOI: 10.1016/j.molmet.2017.05.012


a Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
b Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
c Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA
d Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA
e Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA


Abstract
Background: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasis are not fully understood. Methods & results: Here we show adipocyte DNL controls crosstalk to localized sympathetic neurons that mediate expansion of beige/brite adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes (UCP1-FASNKO mice) cause these effects in iWAT. Conclusions: These results demonstrate that downregulation of fatty acid synthesis via FASN depletion in white adipocytes of mature mice can stimulate neuronal signaling to control thermogenic programming in iWAT. © 2017 The Authors.


Author Keywords
Adipocytes;  De novo lipogenesis;  Glucose homeostasis;  IWAT browning;  Sympathetic nerve activation


Document Type: Article in Press
Source: Scopus

 

12) 

Wilfley, D.E., Fitzsimmons-Craft, E.E., Eichen, D.M.
Binge-eating disorder in adults
(2017) Annals of Internal Medicine, 166 (3), pp. 230-231. 

DOI: 10.7326/L16-0622


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


Document Type: Letter
Source: Scopus

 

13) 

Cabrera-Serrano, M., Junckerstorff, R.C., Alisheri, A., Pestronk, A., Laing, N.G., Weihl, C.C., Lamont, P.J.
Cystinosis distal myopathy, novel clinical, pathological and genetic features
(2017) Neuromuscular Disorders, . Article in Press. 

DOI: 10.1016/j.nmd.2017.05.010


a Centre for Medical Research, University of Western Australia, Harry Perkins Institute of Medical Research, Perth, WA 6009, Australia
b Department of Neurology and Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain
c Section of Neuropathology, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, WA, Australia
d Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia
e Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110
f Neurogenetic Unit, Department of Neurology, Royal Perth Hospital, Perth, WA 6000, Australia


Abstract
Nephropathic cystinosis is an autosomal recessive lysosomal disease in which cystine cannot exit the lysosome to complete its degradation in the cytoplasm, thus accumulating in tissues. Some patients develop a distal myopathy involving mainly hand muscles. Myopathology descriptions from only 5 patients are available in the literature. We present a comprehensive clinical, pathological and genetic description of 3 patients from 2 families with nephropathic cystinosis. Intrafamiliar variability was detected in one family in which one sibling developed a severe distal myopathy while the other sibling did not show any signs of skeletal muscle involvement. One of the patients was on treatment with Cysteamine for over 12 years but still developed the usual complications of nephropathic cystinosis in his twenties. Novel pathological findings consisting in sarcoplasmic deposits reactive for slow myosin were identified. Three previously known and one novel mutation are reported. Nephropathic cystinosis should be included in the differential diagnosis of distal myopathies in those with early renal failure. Novel clinical and pathological features are reported here contributing to the characterization of the muscle involvement in nephropathic cystinosis. © 2017 Elsevier B.V.


Author Keywords
CTNS;  Cystinosis;  Distal myopathy;  Slow myosin


Document Type: Article in Press
Source: Scopus

 

14) 

Gross, A.L., Hassenstab, J.J., Johnson, S.C., Clark, L.R., Resnick, S.M., Kitner-Triolo, M., Masters, C.L., Maruff, P., Morris, J.C., Soldan, A., Pettigrew, C., Albert, M.S.
A classification algorithm for predicting progression from normal cognition to mild cognitive impairment across five cohorts: The preclinical AD consortium
(2017) Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 8, pp. 147-155. 

DOI: 10.1016/j.dadm.2017.05.003


a Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
b Johns Hopkins University Center on Aging and Health, Baltimore, MD, United States
c Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
d Wisconsin Alzheimer's Institute and Alzheimer's Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, United States
e Geriatric Research Education and Clinical Center, William S Middleton Veterans Memorial Hospital, Madison, WI, United States
f Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore, MD, United States
g The Florey Institute, University of Melbourne, Australia
h Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States


Abstract
Introduction We established a method for diagnostic harmonization across multiple studies of preclinical Alzheimer's disease and validated the method by examining its relationship with clinical status and cognition. Methods Cognitive and clinical data were used from five studies (N = 1746). Consensus diagnoses established in each study used criteria to identify progressors from normal cognition to mild cognitive impairment. Correspondence was evaluated between these consensus diagnoses and three algorithmic classifications based on (1) objective cognitive impairment in 2+ tests only; (2) a Clinical Dementia Rating (CDR) of ≥0.5 only; and (3) both. Associations between baseline cognitive performance and cognitive change were each tested in relation to progression to algorithm-based classifications. Results In each study, an algorithmic classification based on both cognitive testing cutoff scores and a CDR ≥0.5 provided optimal balance of sensitivity and specificity (areas under the curve: 0.85–0.95). Over an average 6.6 years of follow-up (up to 28 years), N = 186 initially cognitively normal participants aged on average 64 years at baseline progressed (incidence rate: 15.3 people/1000 person-years). Baseline cognitive scores and cognitive change were associated with future diagnostic status using this algorithmic classification. Discussion Both cognitive tests and CDR ratings can be combined across multiple studies to obtain a reliable algorithmic classification with high specificity and sensitivity. This approach may be applicable to large cohort studies and to clinical trials focused on preclinical Alzheimer's disease because it provides an alternative to implementation of a time-consuming adjudication panel. © 2017 The Authors


Author Keywords
Cognitive testing;  Diagnostic classification;  Harmonization;  Longitudinal follow-up;  Preclinical Alzheimer's disease


Document Type: Article
Source: Scopus

 

15) 

Howard, S.W., Zhang, Z., Buchanan, P., Armbrecht, E., Williams, C., Wilson, G., Hutchinson, J., Pearson, L., Ellsworth, S., Byler, C.M., Loux, T., Wang, J., Bernell, S., Holekamp, N.
The Effect of a Comprehensive Care Transition Model on Cost and Utilization for Medically Complex Children With Cerebral Palsy
(2017) Journal of Pediatric Health Care, . Article in Press. 

DOI: 10.1016/j.pedhc.2017.04.017


a Saint Louis University, Health Management and Policy, St. Louis, MO
b Abdominal Transplant Center, Saint Louis University School of Medicine, St. Louis, MO
c Statistical Data Analyst, Washington University School of Medicine, St. Louis, MO
d University of Iowa College of Public Health, Iowa City, IA
e Consumer Safety Officer, U.S. Food and Drug Administration, St. Louis, MO
f Operations Project Consultant, St. Luke's Health System, Kansas City, MO
g Data Analyst, St. Louis Children's Hospital, St. Louis, MO
h University of Texas MD Anderson Cancer Center, Houston, TX
i Department of Biostatistics, Saint Louis University, St. Louis, MO
j Health Management and Policy, Oregon State University, Corvallis, OR
k Ranken Jordan Pediatric Bridge Hospital, Maryland Heights, MO


Abstract
Introduction: Our aim was to evaluate cost and acute care utilization related to an organized approach to care coordination and transitional care after major acute care hospitalization for children with medical complexities, including cerebral palsy. Methods: A retrospective cohort of 32 patients from Ranken Jordan Pediatric Bridge Hospital (RJPBH) who received the Care Beyond the Bedside model was compared with 151 patients receiving standard care elsewhere across Missouri. Claims data (2007-2012) were obtained from MoHealthNet, Missouri's Medicaid program, for all children with moderate to severe cerebral palsy (defined using approximated Gross Motor Function Classification System levels) who had at least one hospital visit during the study period (N = 183). Risk-adjusted linear and Poisson regression models were used to analyze per-member-per-month costs and three indicators of acute care utilization (emergency department visits, readmissions, and inpatient days). Results: RJPBH patients were associated with statistically significant reductions in per-member-per-month costs (-21%), hospital readmissions (-66%), and inpatient days (-57%). Discussion: RJPBH's enhanced interprofessional medical home-like model, including intense care coordination, psychosocial therapy, family and caregiver empowerment, and transitional care, may be keys to reducing cost and unnecessary hospital use for children with medical complexities with cerebral palsy who receive Medicaid. © 2017 National Association of Pediatric Nurse Practitioners.


Author Keywords
Care beyond the bedside;  Care coordination;  Children with medical complexity;  Economic evaluation;  Medical home;  Outcomes research;  Transitional care


Document Type: Article in Press
Source: Scopus

 

16) 

Potter, C., Zhu, W., Razafsky, D., Ruzycki, P., Kolesnikov, A.V., Doggett, T., Kefalov, V.J., Betleja, E., Mahjoub, M.R., Hodzic, D.
Multiple Isoforms of Nesprin1 Are Integral Components of Ciliary Rootlets
(2016) Current Biology, . Article in Press. 

DOI: 10.1016/j.cub.2017.05.066


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA
b Division of Nephrology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA


Abstract
SYNE1 (synaptic nuclear envelope 1) encodes multiple isoforms of Nesprin1 (nuclear envelope spectrin 1) that associate with the nuclear envelope (NE) through a C-terminal KASH (Klarsicht/Anc1/Syne homology) domain (A) []. This domain interacts directly with the SUN (Sad1/Unc84) domain of Sun proteins [], a family of transmembrane proteins of the inner nuclear membrane (INM) [], to form the so-called LINC complexes (linkers of the nucleoskeleton and cytoskeleton) that span the entire NE and mediate nuclear positioning []. In a stark departure from this classical depiction of Nesprin1 in the context of the NE, we report here that rootletin recruits Nesprin1α at the ciliary rootlets of photoreceptors and identify asymmetric NE aggregates of Nesprin1α and Sun2 that dock filaments of rootletin at the nuclear surface. In NIH 3T3 cells, we show that recombinant rootletin filaments also dock to the NE through the specific recruitment of an 
600-kDa endogenous isoform of Nesprin1 (Nes1600kDa) and of Sun2. In agreement with the association of Nesprin1α with photoreceptor ciliary rootlets and the functional interaction between rootletin and Nesprin1 in fibroblasts, we demonstrate that multiple isoforms of Nesprin1 are integral components of ciliary rootlets of multiciliated ependymal and tracheal cells. Together, these data provide a novel functional paradigm for Nesprin1 at ciliary rootlets and suggest that the wide spectrum of human pathologies linked to truncating mutations of SYNE1 [] may originate in part from ciliary defects. Potter et al. report a novel interaction between Nesprin1 and rootletin that underlies the localization of multiple isoforms of Nesprin1 to ciliary rootlets and the docking of rootletin filaments at the nuclear surface by Sun2/Nesprin1 LINC complexes. This new paradigm may explain how mutations of SYNE1 underlie multisystemic human pathologies. © 2017 Elsevier Ltd.


Author Keywords
Basal bodies;  Cilia;  LINC complexes;  Nesprin1;  Nesprin2;  Nuclear envelope;  Photoreceptors;  Retina;  Rootletin;  Rootlets;  Sun1;  Sun2;  SYNE1


Document Type: Article in Press
Source: Scopus