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

Neuroscience Publications Archive - October 2017

Weekly Scopus Report:

 

October 30, 2017

October 23, 2017

October 16, 2017

October 9, 2017

October 2, 2017

 

October 30, 2017

1) 

Bhalla, S., Lin, K.H., Tang, S.Y.
Postnatal development of the murine notochord remnants quantified by high-resolution contrast-enhanced MicroCT
(2017) Scientific Reports, 7 (1), art. no. 13361, . 

DOI: 10.1038/s41598-017-13446-5


a Department of Biology, Washington University, St. Louis, MO, United States
b Department of Orthopaedic Surgery, Washington University, St. Louis, MO, United States
c Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
d Department of Materials Science and Mechanical Engineering, Washington University, St. Louis, MO, United States


Abstract
The notochord gives rise to spinal segments during development, and it becomes embedded within the nucleus pulposus of the intervertebral disc (IVD) during maturation. The disruption of the notochord band has been observed with IVD degeneration. Since the mechanical competence of the IVD relies on its structural constituents, defining the structure of the notochord during aging is critical for investigations relating to IVD function and homeostasis. The assessment and imaging of the notochord has classically relied on histological techniques, which introduces sectioning artifacts during preparation and spatial biases. Magnetic resonance imaging (MRI) does not offer sufficient resolution to discriminate the notochord from the surrounding the nucleus pulposus, especially in murine models. Current X-ray based computed tomography systems provide imaging resolutions down to the single- and sub- micron scales, and when coupled with contrast-enhancing agents, enable the high-resolution three-dimensional imaging of relatively small features. Utilizing phosphomolybdic acid to preferentially bind to collagen cationic domains, we describe the structure of the notochord remnants with aging in the lumbar IVDs of BALB/c mice. These results provide a highly quantitative and sensitive approach to monitoring the IVD during postnatal development. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

2) 

Husa, R.A., Gordon, B.A., Cochran, M.M., Bertolin, M., Bond, D.N., Kirchhoff, B.A.
Left caudal middle frontal gray matter volume mediates the effect of age on self-initiated elaborative encoding strategies
(2017) Neuropsychologia, 106, pp. 341-349. 

DOI: 10.1016/j.neuropsychologia.2017.10.004


a Department of Psychology, Saint Louis University, St. Louis, MO, United States
b Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Aging is associated with decreased self-initiated use of effective elaborative encoding strategies. Little is currently known regarding what factors drive age differences in self-initiated encoding strategies. The present research investigated whether age differences in prefrontal gray matter integrity contribute to age differences in self-initiated elaborative encoding strategies. The relationships between age, prefrontal regional gray matter volumes, and overall use of self-initiated elaborative encoding strategies were examined in healthy younger and older adults. Gray matter volume was calculated from structural MRI scans using Freesurfer. Encoding strategy use was assessed by retrospective item-by-item strategy self-reports given after a verbal intentional encoding task. Left caudal middle frontal gray matter volume mediated the effect of age on overall self-initiated use of elaborative encoding strategies. This suggests that age-associated declines in prefrontal gray matter integrity significantly contribute to age-associated declines in effective encoding strategies. © 2017 Elsevier Ltd


Author Keywords
Aging;  Encoding;  Gray matter volume;  Memory;  Strategy use


Document Type: Article
Source: Scopus

 

3) 

Durkin, M.S., Maenner, M.J., Baio, J., Christensen, D., Daniels, J., Fitzgerald, R., Imm, P., Lee, L.-C., Schieve, L.A., Van Naarden Braun, K., Wingate, M.S., Yeargin-Allsopp, M.
Autism spectrum disorder among US children (2002-2010): Socioeconomic, racial, and ethnic disparities
(2017) American Journal of Public Health, 107 (11), pp. 1818-1826. 

DOI: 10.2105/AJPH.2017.304032


a Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Waisman Center of the University of Wisconsin-Madison, 610 Walnut St, Madison, WI, United States
b National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, United States
c Department of Epidemiology, University of North Carolina, Gillings School of Global Public Health, Chapel Hill, NC, United States
d Department of Psychiatry, Washington University, St. Louis, MO, United States
e Waisman Center of the University of Wisconsin-Madison, Madison, WI, United States
f Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
g Department of Health Care Organization and Policy, University of Alabama at Birmingham, School of Public Health, Birmingham, AL, United States


Abstract
Objectives. To describe the association between indicators of socioeconomic status (SES) and the prevalence of autism spectrum disorder (ASD) in the United States during the period 2002 to 2010, when overall ASD prevalence among children more than doubled, and to determine whether SES disparities account for ongoing racial and ethnic disparities in ASD prevalence. Methods. We computed ASD prevalence and 95% confidence intervals (CIs) from population-based surveillance, census, and survey data. We defined SES categories by using area-level education, income, and poverty indicators.Weascertained ASD in 13 396 of 1 308 641 8-year-old children under surveillance. Results. The prevalence of ASD increased with increasing SES during each surveillance year amongWhite, Black, and Hispanic children.The prevalence difference between highand low-SES groups was relatively constant over time (3.9/1000 [95% CI = 3.3, 4.5] in 2002 and 4.1/1000 [95% CI = 3.6, 4.6] in the period 2006-2010). Significant racial/ethnic differences in ASD prevalence remained after stratification by SES. Conclusions. A positive SES gradient in ASD prevalence according to US surveillance data prevailed between 2002 and 2010, and racial and ethnic disparities in prevalence persisted during this time among low-SES children.


Document Type: Article
Source: Scopus

 

4) 

Holehouse, A.S., Pappu, R.V.
FUS Zigzags Its Way to Cross Beta
(2017) Cell, 171 (3), pp. 499-500. 

DOI: 10.1016/j.cell.2017.10.007


Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in Saint Louis, Saint Louis, MO, United States


Abstract
The low-complexity domain (LCD) of the FUS protein forms concentration-dependent assemblies, including liquid droplets and fibril-based hydrogels. The molecular structures of FUS within different assemblies and their functional relevance are subjects of intense debate. Murray et al. report an atomic-level structural model for FUS LCD fibrils that answers some questions and raises new ones. The low-complexity domain (LCD) of the FUS protein forms concentration-dependent assemblies, including liquid droplets and fibril-based hydrogels. The molecular structures of FUS within different assemblies and their functional relevance are subjects of intense debate. Murray et al. report an atomic-level structural model for FUS LCD fibrils that answers some questions and raises new ones. © 2017 Elsevier Inc.


Document Type: Short Survey
Source: Scopus

 

5) 

Fernandez, E., Dejnirattisai, W., Cao, B., Scheaffer, S.M., Supasa, P., Wongwiwat, W., Esakky, P., Drury, A., Mongkolsapaya, J., Moley, K.H., Mysorekar, I.U., Screaton, G.R., Diamond, M.S.
Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection
(2017) Nature Immunology, 18 (11), pp. 1261-1269. 

DOI: 10.1038/ni.3849


a Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
b Division of Immunology and Inflammation, Department of Medicine, Hammersmith Campus, Imperial College, London, United Kingdom
c Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, United States
d Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok, Thailand
e Medical Sciences Divisional Office, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
f Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
g Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States
h Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The Zika virus (ZIKV) epidemic has resulted in congenital abnormalities in fetuses and neonates. Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV infection in mice, those recognizing the DENV E-dimer epitope (EDE) can neutralize ZIKV infection in cell culture. We evaluated the therapeutic activity of human monoclonal antibodies to DENV EDE for their ability to control ZIKV infection in the brains, testes, placentas, and fetuses of mice. A single dose of the EDE1-B10 antibody given 3 d after ZIKV infection protected against lethality, reduced ZIKV levels in brains and testes, and preserved sperm counts. In pregnant mice, wild-type or engineered LALA variants of EDE1-B10, which cannot engage Fcg receptors, diminished ZIKV burden in maternal and fetal tissues, and protected against fetal demise. Because neutralizing antibodies to EDE have therapeutic potential against ZIKV, in addition to their established inhibitory effects against DENV, it may be possible to develop therapies that control disease caused by both viruses. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.


Document Type: Article
Source: Scopus

 

6) 

Smallfield, S., Berger, S., Hillman, B., Saltzgaber, P., Giger, J., Kaldenberg, J.
Living with Low Vision: Strategies Supporting Daily Activity
(2017) Occupational Therapy in Health Care, pp. 1-17. Article in Press. 

DOI: 10.1080/07380577.2017.1384969


a Program in Occupational Therapy, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
b Department of Occupational Therapy, Boston University College of Health & Rehabilitation Sciences, Sargent College, Boston, MA, USA
c Aegis Therapies, Sioux Falls, SD, USA
d Central Nebraska Rehabilitation Services, Grand Island, NE, USA
e College of Social Work, University of Kentucky, Lexington, KY, USA


Abstract
The purpose of this research was to describe the strategies that older adults with low vision use to support daily living. A descriptive qualitative study of 10 older adults with low vision was conducted using semistructured, audio-recorded interviews. The data was coded and grouped into categories, and the findings were summarized. Four major themes were identified: (a) device nonuse; (b) sensory strategies and devices; (c) environmental strategies; and (d) resourcefulness. Older adults with low vision try many devices and strategies to find the ones that allow them to participate in meaningful activity within their physical and social environment. These findings support the use of a client-centered, multicomponent, problem-solving approach to low vision rehabilitation to maximize performance of daily activity despite declining vision. © 2017 Taylor & Francis Group, LLC


Author Keywords
Assistive technology;  environment;  low vision;  older adults;  problem solving


Document Type: Article in Press
Source: Scopus

 

7) 

Warner, J.B., Ruff, K.M., Tan, P.S., Lemke, E.A., Pappu, R.V., Lashuel, H.A.
Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths
(2017) Journal of the American Chemical Society, 139 (41), pp. 14456-14469. 

DOI: 10.1021/jacs.7b06659


a Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
b Department of Biomedical Engineering, Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
c Structural and Computational Biology Unit, Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany


Abstract
Huntington's disease is caused by expansion of a polyglutamine (polyQ) domain within exon 1 of the huntingtin gene (Httex1). The prevailing hypothesis is that the monomeric Httex1 protein undergoes sharp conformational changes as the polyQ length exceeds a threshold of 36-37 residues. Here, we test this hypothesis by combining novel semi-synthesis strategies with state-of-the-art single-molecule Förster resonance energy transfer measurements on biologically relevant, monomeric Httex1 proteins of five different polyQ lengths. Our results, integrated with atomistic simulations, negate the hypothesis of a sharp, polyQ length-dependent change in the structure of monomeric Httex1. Instead, they support a continuous global compaction with increasing polyQ length that derives from increased prominence of the globular polyQ domain. Importantly, we show that monomeric Httex1 adopts tadpole-like architectures for polyQ lengths below and above the pathological threshold. Our results suggest that higher order homotypic and/or heterotypic interactions within distinct sub-populations of neurons, which are inevitable at finite cellular concentrations, are likely to be the main source of sharp polyQ length dependencies of HD. © 2017 American Chemical Society.


Document Type: Article
Source: Scopus

 

8) 

Wang, H., Rempel, D.L., Giblin, D., Frieden, C., Gross, M.L.
Peptide-Level Interactions between Proteins and Small-Molecule Drug Candidates by Two Hydrogen-Deuterium Exchange MS-Based Methods: The Example of Apolipoprotein E3
(2017) Analytical Chemistry, 89 (20), pp. 10687-10695. 

DOI: 10.1021/acs.analchem.7b01121


a Department of Chemistry, Washington University in St. Louis, One Brookings Drive, St. Louis, MO, United States
b Department of Biochemistry and Molecular Biophysics, School of Medicine, Washington University in St. Louis, 660 South Euclid Avenue, St. Louis, MO, United States
c Analytical Research and Development, Pfizer Incorporated, Chesterfield, MO, United States


Abstract
We describe a platform utilizing two methods based on hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (MS) to characterize interactions between a protein and a small-molecule ligand. The model system is apolipoprotein E3 (apoE3) and a small-molecule drug candidate. We extended PLIMSTEX (protein-ligand interactions by mass spectrometry, titration, and H/D exchange) to the regional level by incorporating enzymatic digestion to acquire binding information for peptides. In a single experiment, we not only identified putative binding sites, but also obtained affinities of 6.0, 6.8, and 10.6 μM for the three different regions, giving an overall binding affinity of 7.4 μM. These values agree well with literature values determined by accepted methods. Unlike those methods, PLIMSTEX provides site-specific binding information. The second approach, modified SUPREX (stability of unpurified proteins from rates of H/D exchange) coupled with electrospray ionization (ESI), allowed us to obtain detailed understanding about apoE unfolding and its changes upon ligand binding. Three binding regions, along with an additional site, which may be important for lipid binding, show increased stability (less unfolding) upon ligand binding. By employing a single parameter, ΔC1/2%, we compared relative changes of denaturation between peptides. This integrated platform provides information orthogonal to commonly used HDX kinetics experiments, providing a general and novel approach for studying protein-ligand interactions. (Figure Presented). © 2017 American Chemical Society.


Document Type: Article
Source: Scopus

 

9) 

Goedeken, S., Potempa, C., Prager, E.M., Foster, E.R.
Encoding strategy training and self-reported everyday prospective memory in people with Parkinson disease: a randomized-controlled trial
(2017) Clinical Neuropsychologist, pp. 1-21. Article in Press. 

DOI: 10.1080/13854046.2017.1387287


a Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, USA
b Occupational Therapy Program, Maryville University College of Health Professions, St. Louis, MO, USA
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA


Abstract
Objective: To compare the effects of laboratory-based training in implementation intentions (II; experimental strategy) and verbal rehearsal (VR; control strategy) on self-reported everyday prospective memory among people with Parkinson disease (PD) and to investigate potential correlates of change in self-reported everyday prospective memory in response to this training. Method: This was a randomized-controlled trial. Participants with mild to moderate PD without dementia underwent one session of training in either II (n = 25) or VR (n = 27). Then they were instructed to use their strategy as much as possible in their everyday lives to help them remember to do things. The Prospective and Retrospective Memory Questionnaire Prospective Scale (PRMQ-Pro) administered at baseline and one month after training assessed training-related change in self-reported everyday prospective memory. Baseline depressive symptoms, perceptions of the strategy (credibility, expectancy), prospective memory-related awareness, global cognition, and disease severity were correlated to PRMQ-Pro Change scores (post minus pre) to determine their association with response to training. Results: The VR group’s PRMQ-Pro scores declined from pre to post training, while the II group’s remained stable (p = .03). This effect was driven by change in self-cued everyday prospective memory tasks. Higher baseline depressive symptoms, treatment expectancy, and global cognition related to better response to training in the II group (rs ≤ −.40, ps ≤ .05). Conclusions: II training may prevent everyday prospective memory decline among people with PD. In addition, people with higher depression, stronger expectations of improvement from strategy training, or better global cognition may benefit the most from II training. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
cognitive rehabilitation;  executive function;  memory;  Parkinson disease;  randomized-controlled trial


Document Type: Article in Press
Source: Scopus

 

10) 

Hwang, H.G., Marrus, N., Irvin, K., Markson, L.
Three-Year-Old Children Detect Social Exclusion in Third-Party Interactions
(2017) Journal of Cognition and Development, pp. 1-15. Article in Press. 

DOI: 10.1080/15248372.2017.1368517


Washington University in St. Louis


Abstract
Humans are motivated to connect with others and are sensitive to social exclusion—intentionally leaving out others. This ability to detect social exclusion is suggested to be evolutionarily adaptive, biologically hardwired, and an important feature of social-cognitive development. Yet it is unclear when children start to independently detect social exclusion. Previous developmental research on social exclusion has focused on children older than 4 years of age, but recent infancy research has suggested younger children may be able to process complex social interactions such as social exclusion. The present study is the first to examine whether 2- to 3-year-old children detect social exclusion and if they prefer to affiliate with individuals who have been excluded over individuals who exclude others. Across 2 experiments, 2- and 3-year-old children (N = 140) viewed exclusive group interactions, in which 2 agents unjustly excluded 1 agent, and children were asked to choose whether they preferred to play with an excluded agent or an exclusive agent. Three-year-old children consistently preferred to play with the excluded agent, whereas 2-year-old children showed no preference. Three-year-old children did not show a preference among agents engaged in inclusive interactions and did not prefer an agent who refused to engage with a group, showing that 3-year-old children distinguish unjust exclusion from other types of interactions. Together, these findings suggest 3-year-old children detect social exclusion and are motivated to affiliate with unjustly excluded agents over those who exclude others, whereas these capacities are still developing in 2-year-old children. © 2017 Taylor & Francis


Document Type: Article in Press
Source: Scopus

 

11) 

Janssen, E., Ruiter, R.A.C., Waters, E.A.
Combining risk communication strategies to simultaneously convey the risks of four diseases associated with physical inactivity to socio-demographically diverse populations
(2017) Journal of Behavioral Medicine, pp. 1-15. Article in Press. 

DOI: 10.1007/s10865-017-9894-3


a Department of Work and Social Psychology, Faculty of Psychology and Neuroscience, Maastricht University, P.O. Box 616, Maastricht, Netherlands
b School of Medicine, Department of Surgery (Division of Public Health Sciences), Washington University in Saint Louis, 600 S. Euclid Ave, Campus Box 8100, Saint Louis, MO, United States


Abstract
A single risk factor can increase the risk of developing multiple diseases, but most risk communication research has been conducted in the context of a single disease. We explored which combination of three recommended risk communication strategies is most effective in simultaneously conveying risk estimates of four diseases associated with physical inactivity: colon cancer, stroke, diabetes, and heart disease. Participants (N = 1161, 50% no college experience, 50% racial/ethnic minority) were shown hypothetical risk estimates for each of the four diseases. All four diseases were placed at varying heights on 1 of 12 vertical bar charts (i.e., “risk ladders”) to indicate their respective probabilities. The risk ladders varied in a 2 (risk reduction information: present/absent) × 2 (numerical format: words/words and numbers) × 3 (social comparison information: none/somewhat higher than average/much higher than average) full factorial design. Participants were randomly assigned to view one of the risk ladders and then completed a questionnaire assessing message comprehension, message acceptance, physical activity-related risk and efficacy beliefs, and physical activity intentions. Higher message acceptance was found among (1) people who received risk reduction information versus those who did not (p = .01), and (2) people who did not receive social comparison information versus those told that they were at higher than average risk (p = .03). Further, absolute cognitive perceived risk of developing “any of the diseases shown in the picture” was higher among people who did not receive social comparison information (p = .03). No other main effects and only very few interactions with demographic variables were found. Combining recommended risk communication strategies did not improve or impair key cognitive or affective precursors of health behavior change. It might not be necessary to provide people with extensive information when communicating risk estimates of multiple diseases. © 2017 Springer Science+Business Media, LLC


Author Keywords
Decision making;  Health disparities;  Physical activity;  Risk communication


Document Type: Article in Press
Source: Scopus

 

12) 

Boyer, P., Petersen, M.B.
Folk-Economic Beliefs: An Evolutionary Cognitive Model
(2017) Behavioral and Brain Sciences, pp. 1-51. Article in Press. 

DOI: 10.1017/S0140525X17001960


a Washington University in St. Louis
b Aarhus University


Abstract
The domain of “folk-economics” consists in explicit beliefs about the economy held by laypeople, untrained in economics, about such topics as e.g., the causes of the wealth of nations, the benefits or drawbacks of markets and international trade, the effects of regulation, the origins of inequality, the connection between work and wages, the economic consequences of immigration, or the possible causes of unemployment. These beliefs are crucial in forming people's political beliefs, and in shaping their reception of different policies. Yet, they often conflict with elementary principles of economic theory and are often described as the consequences of ignorance, irrationality or specific biases. As we will argue, these past perspectives fail to predict the particular contents of popular folk-economic beliefs and, as a result, there is no systematic study of the cognitive factors involved in their emergence and cultural success. Here we propose that the cultural success of particular beliefs about the economy is predictable if we consider the influence of specialized, largely automatic inference systems that evolved as adaptations to ancestral human small-scale sociality. These systems, for which there is independent evidence, include free-rider detection, fairness-based partner-choice, ownership intuitions, coalitional psychology, and more. Information about modern mass-market conditions activates these specific inference-systems, resulting in particular intuitions, e.g., that impersonal transactions are dangerous or that international trade is a zero-sum game. These intuitions in turn make specific policy proposals more likely than others to become intuitively compelling, and as a consequence exert a crucial influence on political choices. Copyright © Cambridge University Press 2017


Document Type: Article in Press
Source: Scopus

 

13) 

Joynt Maddox, K.E.
Social and behavioral determinants of spending
(2017) JAMA Internal Medicine, 177 (10), pp. 1431-1432. 

DOI: 10.1001/jamainternmed.2017.3325


a Brigham and Women’s Hospital, Boston, MA, United States
b Harvard T. H. Chan School of Public Health, Boston, MA, United States
c Washington University School of Medicine, St Louis, MO, United States


Document Type: Note
Source: Scopus

 

14) 

Trinkaus, E., Villotte, S.
External auditory exostoses and hearing loss in the Shanidar 1 Neandertal
(2017) PLoS ONE, 12 (10), art. no. e0186684, . 

DOI: 10.1371/journal.pone.0186684


a Department of Anthropology, Washington University, Saint Louis, MO, United States
b UMR5199 PACEA, Université de Bordeaux–CNRS, Bâtiment B8, Allée Geoffroy Saint Hilaire, Pessac cedex, France


Abstract
The Late Pleistocene Shanidar 1 older adult male Neandertal is known for the crushing fracture of his left orbit with a probable reduction in vision, the loss of his right forearm and hand, and evidence of an abnormal gait, as well as probable diffuse idiopathic skeletal hyperosto-sis. He also exhibits advanced external auditory exostoses in his left auditory meatus and larger ones with complete bridging across the porus in the right meatus (both Grade 3). These growths indicate at least unilateral conductive hearing (CHL) loss, a serious sensory deprivation for a Pleistocene hunter-gatherer. This condition joins the meatal atresia of the Middle Pleistocene Atapuerca-SH Cr.4 in providing evidence of survival with conductive hearing loss (and hence serious sensory deprivation) among these Pleistocene humans. The presence of CHL in these fossils thereby reinforces the paleobiological and archeological evidence for supporting social matrices among these Pleistocene foraging peoples. © 2017 Trinkaus, Villotte. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Document Type: Article
Source: Scopus

 

15) 

Fick, D.M., Auerbach, A.D., Avidan, M.S., Busby-Whitehead, J., Ely, E.W., Jones, R.N., Marcantonio, E.R., Needham, D.M., Pandharipande, P., Robinson, T.N., Schmitt, E.M., Travison, T.G., Inouye, S.K., the NIDUS Delirium Network
Network for Investigation of Delirium across the U.S.: Advancing the Field of Delirium with a New Interdisciplinary Research Network
(2017) Journal of the American Geriatrics Society, 65 (10), pp. 2158-2160. 

DOI: 10.1111/jgs.14942


a Department of Psychiatry, College of Nursing, College of Medicine, Pennsylvania State University, University Park, PA, United States
b Division of Hospital Medicine, University of California San Francisco, San Francisco, CA, United States
c Department of Anesthesiology, School of Medicine, Washington University, St. Louis, MO, United States
d Division of Geriatric Medicine, Center for Aging and Health, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, United States
e Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Tennessee Valley Health Care Center, Nashville, TN, United States
f Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
g Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN, United States
h Department of Psychiatry and Human Behavior, Department of Neurology, Warren Alpert Medical School, Brown University, Providence, RI, United States
i Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
j School of Medicine, Harvard University, Boston, MA, United States
k Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, United States
l Center for Health Services Research, Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States
m Department of Surgery, School of Medicine, University of Colorado, Aurora, CO, United States
n Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States


Document Type: Editorial
Source: Scopus

 

16) 

Fristoe, T.S., Iwaniuk, A.N., Botero, C.A.
Big brains stabilize populations and facilitate colonization of variable habitats in birds
(2017) Nature Ecology and Evolution, pp. 1-10. Article in Press. 

DOI: 10.1038/s41559-017-0316-2


a Department of Biology, Washington University in St. Louis, St. Louis, MO, United States
b Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Canada


Abstract
The cognitive buffer hypothesis posits that environmental variability can be a major driver of the evolution of cognition because an enhanced ability to produce flexible behavioural responses facilitates coping with the unexpected. Although comparative evidence supports different aspects of this hypothesis, a direct connection between cognition and the ability to survive a variable and unpredictable environment has yet to be demonstrated. Here, we use complementary demographic and evolutionary analyses to show that among birds, the mechanistic premise of this hypothesis is well supported but the implied direction of causality is not. Specifically, we show that although population dynamics are more stable and less affected by environmental variation in birds with larger relative brain sizes, the evolution of larger brains often pre-dated and facilitated the colonization of variable habitats rather than the other way around. Our findings highlight the importance of investigating the timeline of evolutionary events when interpreting patterns of phylogenetic correlation. © 2017 The Author(s)


Document Type: Article in Press
Source: Scopus

 

17) 

Lombe, M., Saltzman, L.Y., Chu, Y., Sinha, A., Nebbitt, V.E.
Cumulative risk and resilience: The roles of comorbid maternal mental health conditions and community cohesion in influencing food security in low-income households
(2017) Social Work in Mental Health, pp. 1-19. Article in Press. 

DOI: 10.1080/15332985.2017.1344756


a School of Social Work, Boston College, Chestnut Hill, Massachusetts, USA
b Paul Baerwald School of Social Work and Social Welfare, Hebrew University, Jerusalem, Israel
c Department of Anthropology, Sociology and Social Work, Seattle University, Seattle, Washington, USA
d The Brown School of Social Work, Washington University in St. Louis, St.Louis, Missouri, USA


Abstract
Maternal caregivers play a critical role in achieving household food security. This study examines the impact of cumulative risk across multiple systems with respect to household food security. Data were drawn from a nationally representative survey of 2,276 mothers. Using step-wise lagged dependent variable logistic regression models we examine the influence of mental health, household, and neighborhood characteristics on household food security. Households headed by caregivers with a single mental health condition were less likely to be food secure as compared to those without mental health concerns. Comorbid mental health diagnoses compounded the risk, and worsened the odds of achieving food security. Perceived community cohesion emerged as a resilience factor that buffered both individual and community risks to food security. The findings emphasize the link between positive maternal mental health and food security, and suggest that communities may have an important protective role in food security. © 2017 Taylor & Francis


Author Keywords
Community cohesion;  exposure to violence;  food security;  maternal mental health;  resilience


Document Type: Article in Press
Source: Scopus

 

18) 

Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O'Loughlin, E., Xu, Y., Fanek, Z., Greco, D.J., Smith, S.T., Tweet, G., Humulock, Z., Zrzavy, T., Conde-Sanroman, P., Gacias, M., Weng, Z., Chen, H., Tjon, E., Mazaheri, F., Hartmann, K., Madi, A., Ulrich, J.D., Glatzel, M., Worthmann, A., Heeren, J., Budnik, B., Lemere, C., Ikezu, T., Heppner, F.L., Litvak, V., Holtzman, D.M., Lassmann, H., Weiner, H.L., Ochando, J., Haass, C., Butovsky, O.
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases
(2017) Immunity, 47 (3), pp. 566-581.e9. Cited 1 time.

DOI: 10.1016/j.immuni.2017.08.008


a Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
b Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
c Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, United States
d Center for Brain Research, Medical University of Vienna, Vienna, Austria
e Department of Medicine, Icahn School of Medicine at Mount SinaiNY, United States
f Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, United States
g German Center for Neurodegenerative Diseases, Munich, Germany
h Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, United States
i Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
j Mass Spectrometry and Proteomics Resource Laboratory, Faculty of Arts and Sciences Division of Science, Harvard University, Cambridge MA, United States
k Department of Pharmacology and Experimental Therapeutics and Department of Neurology, Boston University School of MedicineMA, United States
l Department of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany
m Cluster of Excellence, NeuroCure, Charitéplatz 1, Berlin, Germany
n Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
o Biomedical Center, Biochemistry, Ludwig-Maximilians-Universität Munich, Munich, Germany
p Munich Cluster for Systems Neurology, Munich, Germany


Abstract
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons. TREM2 (triggering receptor expressed on myeloid cells 2) induced APOE signaling, and targeting the TREM2-APOE pathway restored the homeostatic signature of microglia in ALS and AD mouse models and prevented neuronal loss in an acute model of neurodegeneration. APOE-mediated neurodegenerative microglia had lost their tolerogenic function. Our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target that could aid in the restoration of homeostatic microglia. Microglia change their phenotype and function during aging and neurodegeneration, but the underlying molecular mechanisms for this change remain unknown. Krasemann et al. identify the TREM2-APOE pathway as a major regulator of microglia phenotypic change in neurodegenerative diseases and suggest that targeting this pathway could restore homeostatic microglia. © 2017 Elsevier Inc.


Author Keywords
Alzheimer's disease;  amyotrophic lateral sclerosis;  APOE;  microglia;  multiple sclerosis;  neurodegeneration;  transcriptional regulation;  TREM2


Document Type: Article
Source: Scopus

 

19) 

Bierut, L.J., Johnson, E.O.
A commentary on Maes et al. "A genetic epidemiological mega analysis of smoking initiation in adolescents"
(2017) Nicotine and Tobacco Research, 19 (9), pp. 1116-1117. Cited 1 time.

DOI: 10.1093/ntr/ntx022


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Fellows Program, RTI International, Research Triangle Park, Chapel Hill, NC, United States


Document Type: Note
Source: Scopus

 

20) 

Tarantola, M.E., Heath, A.C., Sher, K.J., Piasecki, T.M.
WISDM primary and secondary dependence motives: Associations with smoking rate, craving, and cigarette effects in the natural environment
(2017) Nicotine and Tobacco Research, 19 (9), pp. 1073-1079. 

DOI: 10.1093/ntr/ntx027


a Department of Psychological Sciences, University of Missouri, Columbia, MO, United States
b Alcoholism Research Center, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Introduction: The Wisconsin Inventory of Smoking Dependence Motives (WISDM) is a multidimensional measure of smoking motives that was developed to facilitate research aiming to refine the nomological network surrounding tobacco dependence. Recent evidence suggests that a composite of four subscales, termed the Primary Dependence Motives (PDM), may represent core features of advanced addiction, while the remaining nine subscales (Secondary Dependence Motives; SDM) represent instrumental motives for cigarette use that may be relevant at any stage of smoking. Methods: A sample of 255 smokers (all regular alcohol users) participated in an ecological momentary assessment study in which they monitored smoking behavior and related experiences for 21 days. Multilevel regression analyses tested how PDM and SDM predicted daily smoking rate, cigarette craving, and appraisals of pleasure and relief of unpleasant feelings from smoking. Results: When PDM and SDM were entered simultaneously, only PDM was related to daily cigarette count, and only SDM predicted reports of craving and relief from unpleasant feelings from smoking. SDM was associated with reports of greater pleasure from smoking and PDM was associated with lower pleasure ratings. The Fagerström Test for Nicotine Dependence (FTND) was related to daily smoking rate and craving, but WISDM composites contributed incremental prediction. Conclusions: The findings confirm that PDM indexes heavier use that is relatively unrelated to immediate consequences of smoking. SDM is not uniquely related to smoking heaviness, but is associated with craving and reports of pleasure and relief of unpleasant feelings derived from smoking during ad lib use. Implications: This study extends the evidence for the distinction between the WISDM PDM and SDM. PDM scores are associated with heavier smoking and are relatively unrelated to immediate consequences of smoking. SDM is more strongly related to craving and reports of smokingderived pleasure and relief of unpleasant feelings during ongoing use in daily life. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.


Document Type: Article
Source: Scopus



21) 

Fallata, A., Salter, A., Tyry, T., Cutter, G.R., Marrie, R.A.
Trigeminal neuralgia commonly precedes the diagnosis of multiple sclerosis
(2017) International Journal of MS Care, 19 (5), pp. 240-246. 

DOI: 10.7224/1537-2073.2016-065


a Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
b Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
c Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States
d Dignity Health, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States
e University of Alabama at Birmingham, Birmingham, United States


Abstract
Background: Trigeminal neuralgia (TN) is a well-recognized cause of facial pain in the general population, and multiple sclerosis (MS) accounts for some of these cases. However, the prevalence of TN in MS is poorly understood. We investigated the prevalence of TN and how often TN is the initial presentation of MS in a large MS cohort. Methods: In 2009, we surveyed participants in the North America Research Committee on Multiple Sclerosis Registry regarding TN, including date of onset and pharmacologic and nonpharmacologic treatments used. We estimated the frequency of TN and the frequency with which TN preceded the diagnosis of MS. We compared the demographic and clinical characteristics of participants who reported TN with those of participants who did not using descriptive statistics and logistic regression. Results: Among 8590 eligible survey respondents, the prevalence of TN was 830 (9.7%). Of these respondents, 588 reported the year when TN was diagnosed. The diagnosis of TN preceded that of MS in 88 respondents (15.0%), and the mean ± SD age at diagnosis of TN was 45.3 ± 11.0 years. The odds of reporting TN were higher in women and those with greater disability and longer disease duration. Pharmacologic treatments were used by 88.3% of respondents; 9.7% underwent surgical interventions. Conclusions: In MS, TN occurs frequently and precedes the diagnosis of MS in 15.0% of individuals. Given the frequency of TN in MS, further epidemiological studies and clinical trials to identify effective pharmacologic and nonpharmacologic therapies for TN in MS are warranted. © 2017 Consortium of Multiple Sclerosis Centers.


Document Type: Article
Source: Scopus

 

22) 

Uner, O., Roediger, H.L.
The Effect of Question Placement on Learning from Textbook Chapters
(2017) Journal of Applied Research in Memory and Cognition, . Article in Press. 

DOI: 10.1016/j.jarmac.2017.09.002


Washington University in St. Louis, United States


Abstract
Retrieval practice enhances learning of short passages, but its effectiveness for authentic educational materials such as textbook chapters is not well established. In the current experiment, students studied a 40-page textbook chapter on biology. Retrieval practice with correct-answer feedback was manipulated within subjects: some questions appeared only after a chapter section, others only after the whole chapter, and yet others at both times. Two groups served as controls: the reread group read the feedback presented in the retrieval practice condition, and the other group simply read the chapter once. Students took a final test two days later. Practicing retrieval resulted in greater recall relative to the two control groups. On the final test, the two single testing conditions produced comparable benefits, but testing twice produced the greatest benefit. Retrieval practice is effective in learning from authentic text material and placement of the initial test does not matter. © 2017 Society for Applied Research in Memory and Cognition.


Author Keywords
Learning from text;  Question placement;  Retrieval practice;  Testing effect


Document Type: Article in Press
Source: Scopus

 

23) 

Tripathi, M., Salunke, P., Mukherjee, K.K., Washington, C.W., Zipfel, G.J.
Sildenafil for cerebral vasospasm: Is the proof of the pudding in the eating?
(2016) Journal of Neurosurgery, 125 (3), pp. 782-783. 

DOI: 10.3171/2016.2.JNS16355


a Chandigarh, India
b University of Mississippi Medical Center, Jackson, MS, United States
c Washington University School of Medicine, Saint Louis, MO, United States


Document Type: Letter
Source: Scopus

 

 

October 23, 2017

1) 

Yoon, H., Belmonte, K.C., Kasten, T., Bateman, R., Kim, J.
Intra-and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery
(2017) Scientific Reports, 7 (1), art. no. 12720, . 

DOI: 10.1038/s41598-017-13031-w


a Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, United States
b Neurobiology of Disease Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
MicroRNAs are emerging as promising biomarkers for diagnosis of various diseases. Notably, cerebrospinal fluid (CSF) contains microRNAs that may serve as biomarkers for neurological diseases. However, there has been a lack of consistent findings among CSF microRNAs studies. Although such inconsistent results have been attributed to various technical issues, inherent biological variability has not been adequately considered as a confounding factor. To address this critical gap in our understanding of microRNA variability, we evaluated intra-individual variability of microRNAs by measuring their levels in the CSF from healthy individuals at two time points, 0 and 48 hours. Surprisingly, the levels of most microRNAs were stable between the two time points. This suggests that microRNAs in CSF may be a good resource for the identification of biomarkers. However, the levels of 12 microRNAs (miR-19a-3p, miR-19b-3p, miR-23a-3p, miR-25a-3p, miR-99a-5p, miR-101-3p, miR-125b-5p, miR-130a-3p, miR-194-5p, miR-195-5p, miR-223-3p, and miR-451a) were significantly altered during the 48 hours interval. Importantly, miRNAs with variable expression have been identified as biomarkers in previous studies. Our data strongly suggest that these microRNAs may not be reliable biomarkers given their intrinsic variability even within the same individual. Taken together, our results provide a critical baseline resource for future microRNA biomarker studies. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

2) 

Lavery, A.M., Waldman, A.T., Charles Casper, T., Roalstad, S., Candee, M., Rose, J., Belman, A., Weinstock-Guttman, B., Aaen, G., Tillema, J.-M., Rodriguez, M., Ness, J., Harris, Y., Graves, J., Krupp, L., Benson, L., Gorman, M., Moodley, M., Rensel, M., Goyal, M., Mar, S., Chitnis, T., Schreiner, T., Lotze, T., Greenberg, B., Kahn, I., Rubin, J., Waubant, E.
Examining the contributions of environmental quality to pediatric multiple sclerosis
(2017) Multiple Sclerosis and Related Disorders, 18, pp. 164-169. 

DOI: 10.1016/j.msard.2017.09.004


a Division of Child Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, United States
b University of Utah, Salt Lake City, UT, United States
c Stony Brook University, Stony Brook, NY, United States
d Buffalo General Hospital, State University of New York at Buffalo, Buffalo, NY, United States
e Loma Linda University Children's Hospital, Loma Linda, CA, United States
f Mayo Clinic, Rochester, MN, United States
g University of Alabama, Tuscaloosa, AL, United States
h University of California San Francisco, San Francisco, CA, United States
i New York University Medical Center, New York, NY, United States
j Boston Children's Pediatric MS Center, Boston, MA, United States
k Cleveland Clinic, Cleveland, OH, United States
l Washington University in St. Louis, St. Louis, MO, United States
m Massachusetts General Hospital, Harvard Medical School, Boston, MS, United States
n Denver Children's Hospital, Denver, CO, United States
o Texas Children's Hospital, Houston, TX, United States
p University of Texas Southwestern Medical Center, Dallas, TX, United States
q Children's National Medical Center, Washington, DC, United States
r Lurie Children's Hospital, Chicago, IL, United States


Abstract
Background Multiple sclerosis (MS) is a presumed autoimmune disease caused by genetic and environmental factors. It is hypothesized that environmental exposures (such as air and water quality) trigger the innate immune response thereby activating a pro-inflammatory cascade. Objective To examine potential environmental factors in pediatric MS using geographic information systems (GIS). Methods Pediatric MS cases and healthy controls were identified as part of an ongoing multicenter case-control study. Subjects’ geographic locations were mapped by county centroid to compare to an Environmental Quality Index (EQI). The EQI examines 5 individual environmental components (air, land, water, social, built factors). A composite EQI score and individual scores were compared between cases and controls, stratified by median proximity to enrollment centers (residence <20 or ≥20 miles from the recruiting center), using logistic regression. Results Of the 287 MS cases and 445 controls, 46% and 49% respectively live in areas where the total EQI is the highest (worst environmental quality). Total EQI was not significantly associated with the odds for MS (p = 0.90 < 20 miles from center; p = 0.43 ≥ 20 miles); however, worsening air quality significantly impacted the odds for MS in those living near a referral center (OR = 2.83; 95%CI 1.5, 5.4) and those who reside ≥ 20 miles from a referral center (OR = 1.61; 95%CI 1.2, 2.3). Conclusion Among environmental factors, air quality may contribute to the odds of developing MS in a pediatric population. Future studies will examine specific air constituents and other location-based air exposures and explore potential mechanisms for immune activation by these exposures. © 2017


Document Type: Article
Source: Scopus

 

3) 

Dierker, D., Roland, J.L., Kamran, M., Rutlin, J., Hacker, C.D., Marcus, D.S., Milchenko, M., Miller-Thomas, M.M., Benzinger, T.L., Snyder, A.Z., Leuthardt, E.C., Shimony, J.S.
Resting-state Functional Magnetic Resonance Imaging in Presurgical Functional Mapping: Sensorimotor Localization
(2017) Neuroimaging Clinics of North America, 27 (4), pp. 621-633. 

DOI: 10.1016/j.nic.2017.06.011


a Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4525 Scott Avenue, Saint Louis, MO, United States
b Department of Neurological Surgery, Washington University School of Medicine, 4525 Scott Avenue, Saint Louis, MO, United States
c Department of Neurology, Washington University School of Medicine, 4525 Scott Avenue, Saint Louis, MO, United States
d Department of Biomedical Imaging, Washington University School of Medicine, 4525 Scott Avenue, Saint Louis, MO, United States


Abstract
This article compares resting-state functional magnetic resonance (fMR) imaging with task fMR imaging for presurgical functional mapping of the sensorimotor (SM) region. Before tumor resection, 38 patients were scanned using both methods. The SM area was anatomically defined using 2 different software tools. Overlap of anatomic regions of interest with task activation maps and resting-state networks was measured in the SM region. A paired t-test showed higher overlap between resting-state maps and anatomic references compared with task activation when using a maximal overlap criterion. Resting state–derived maps are more comprehensive than those derived from task fMR imaging. © 2017 Elsevier Inc.


Author Keywords
Functional MR (fMR);  Multilayer perceptron (MLP);  Resting-state fMR (RS-fMR);  Resting-state networks (RSN);  Sensorimotor network (SMN);  Task fMR (T-MR)


Document Type: Review
Source: Scopus

 

4) 

Shin, D.J., Germann, A.L., Steinbach, J.H., Akk, G.
The Actions of Drug Combinations on the GABAA Receptor Manifest as Curvilinear Isoboles of Additivity
(2017) Molecular pharmacology, 92 (5), pp. 556-563. 

DOI: 10.1124/mol.117.109595


Department of Anesthesiology (D.J.S., A.L.G., J.H.S., G.A.), and the Taylor Family Institute for Innovative Psychiatric Research (J.H.S., G.A.), Washington University School of Medicine in St. Louis, St. Louis, Missouri


Abstract
Drug interactions are often analyzed in terms of isobolograms. In the isobologram, the line connecting the axial points corresponding to the concentrations of two different drugs that produce an effect of the same magnitude is termed an isobole of additivity. Although the isobole of additivity can be a straight line in some special cases, previous work has proposed that it is curvilinear when the two drugs differ in their maximal effects or Hill slopes. Modulators of transmitter-gated ion channels have a wide range of maximal effects as well as Hill slopes, suggesting that the isoboles for drug actions on ion channel function are not linear. In this study, we have conducted an analysis of direct activation and potentiation of the human α1β2γ2L GABAA receptor to demonstrate that: 1) curvilinear isoboles of additivity are predicted by a concerted transition model where the binding of each GABAergic drug additively and independently reduces the free energy of the open receptor compared with the closed receptor; and 2) experimental data for receptor activation using the agonist pair of GABA and propofol or potentiation of responses to a low concentration of GABA by the drug pair of alfaxalone and propofol agree very well with predictions. The approach assuming independent energetic contributions from GABAergic drugs enables, at least for the drug combinations tested, a straightforward method to accurately predict functional responses to any combination of concentrations. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.


Document Type: Article
Source: Scopus

 

5) 

Nicholas, J.G., Geers, A.E.
Sensitivity of expressive linguistic domains to surgery age and audibility of speech in preschoolers with cochlear implants
(2017) Cochlear Implants International, pp. 1-12. Article in Press. 

DOI: 10.1080/14670100.2017.1380114


a Department of Otolaryngology, Washington University School of Medicine, Box 8115, 660 S. Euclid Ave., St. Louis, MO 63130, USA
b School of Behavioral and Brain Sciences, The University of Texas at Dallas, GR41, 800 West Campbell Rd., Richardson, TX 75080, USA


Abstract
Objectives: To determine whether relative delays among domains exist in the conversational use of vocabulary, syntax, and morphology by children with cochlear implants (CIs) and whether these were differentially affected by age of implantation (AOI) and the audibility of speech. Methods: Participants in this short-term longitudinal study were 126 children with AOI of 6–38 months and a matched group of 30 children without hearing loss. Language samples of the same children at ages 3.5 and 4.5 were analyzed for the breadth of vocabulary and bound morphemes used, and sentence length. Results: At both test ages, expressive language domains were delayed equally. Higher performance across domains was independently associated with younger AOI and better pre-implant-aided thresholds. No domain was affected differently by very early implantation, but bound morpheme breadth was associated with better CI-aided thresholds. Between 63 and 78% of children with AOI of 6–11 months scored close to hearing age-mates by 4.5, a level achieved by fewer than 25% of those with AOI of 19–24 months or later ages. Discussion: Previous studies indicated greater language delays in the areas of morphology and syntax than those of vocabulary, with the earliest ages of implantation conferring the greatest benefit to those domains. The current design addressed inconsistency across studies in modes of communication used, presence/absence of other disabilities, and differences in language domains chosen as outcome measures. Conclusions: Linguistic domains benefitted equally from early implantation, regardless of the duration of auditory stimulation. Better pre-CI-aided hearing often compensated for later AOI. Bound morpheme use was greater with better CI-aided thresholds. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
Audibility;  Cochlear implant;  Deafness;  Expressive language development;  Morphology;  Pediatric;  Syntax;  Vocabulary


Document Type: Article in Press
Source: Scopus

 

6) 

Wang, C., Ward, M.E., Chen, R., Liu, K., Tracy, T.E., Chen, X., Xie, M., Sohn, P.D., Ludwig, C., Meyer-Franke, A., Karch, C.M., Ding, S., Gan, L.
Scalable Production of iPSC-Derived Human Neurons to Identify Tau-Lowering Compounds by High-Content Screening
(2017) Stem Cell Reports, 9 (4), pp. 1221-1233. 

DOI: 10.1016/j.stemcr.2017.08.019


a Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA, United States
b Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, CA, United States
c Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA, United States
d Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, CA, United States
e National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD, United States
f Department of Psychiatry, Washington University School of Medicine, 425 South Euclid Avenue, St. Louis, MO, United States


Abstract
Lowering total tau levels is an attractive therapeutic strategy for Alzheimer's disease and other tauopathies. High-throughput screening in neurons derived from human induced pluripotent stem cells (iPSCs) is a powerful tool to identify tau-targeted therapeutics. However, such screens have been hampered by heterogeneous neuronal production, high cost and low yield, and multi-step differentiation procedures. We engineered an isogenic iPSC line that harbors an inducible neurogenin 2 transgene, a transcription factor that rapidly converts iPSCs to neurons, integrated at the AAVS1 locus. Using a simplified two-step protocol, we differentiated these iPSCs into cortical glutamatergic neurons with minimal well-to-well variability. We developed a robust high-content screening assay to identify tau-lowering compounds in LOPAC and identified adrenergic receptors agonists as a class of compounds that reduce endogenous human tau. These techniques enable the use of human neurons for high-throughput screening of drugs to treat neurodegenerative disease. Gan and colleagues developed a simple and scalable technology to generate a large quantity of homogeneous glutamatergic cortical neurons by engineering a neurogenin 2-expressing cassette to the AAVS1 locus of iPSCs. They developed a high-content screening assay and identified adrenergic receptor agonists as a class of compounds that lower endogenous human tau, a key pathogenic factor in Alzheimer's disease. © 2017 The Author(s)


Author Keywords
adrenergic receptor;  Alzheimer's disease;  frontotemporal dementia;  high-content screening;  human induced pluripotent stem cells;  human neurons;  neurodegeneration;  neurogenin 2;  tau;  Tau-lowering


Document Type: Article
Source: Scopus

 

7) 

Panneton, W.M., Pan, B., Gan, Q.
Somatotopy in the medullary dorsal horn as a basis for orofacial reflex behavior
(2017) Frontiers in Neurology, 8 (OCT), art. no. 522, . 

DOI: 10.3389/fneur.2017.00522


a Department of Anesthesiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
b Department of Pharmacological and Physiological Science, School of Medicine, Saint Louis University, St. Louis, MO, United States
c Department of Anesthesiology, Hunan Provincial People's Hospital, Changsha, China


Abstract
The somatotopy of the trigeminocervical complex of the rat was defined as a basis for describing circuitry for reflex behaviors directed through the facial motor nucleus. Thus, transganglionic transport of horseradish peroxidase conjugates applied to individual nerves/peripheral receptive fields showed that nerves innervating oropharyngeal structures projected most rostrally, followed by nerves innervating snout, periocular, and then periauricular receptive fields most caudally. Nerves innervating mucosae or glabrous receptive fields terminated densely in laminae I, II, and V of the trigeminocervical complex, while those innervating hairy skin terminated in laminae I-V. Projections to lamina II exhibited the most focused somatotopy when individual cases were compared. Retrograde transport of FluoroGold (FG) deposited into the facial motor nucleus resulted in labeled neurons almost solely in lamina V of the trigeminocervical complex. The distribution of these labeled neurons paralleled the somatotopy of primary afferent fibers, e.g., those labeled after FG injections into a functional group of motoneurons innervating lip musculature were found most rostrally while those labeled after injections into motoneurons innervating snout, periocular and preauricular muscles, respectively, were found at progressively more caudal levels. Anterograde transport of injections of biotinylated dextran amine into lamina V at different rostrocaudal levels of the trigeminocervical complex confirmed the notion that the somatotopy of orofacial sensory fields parallels the musculotopy of facial motor neurons. These data suggest that neurons in lamina V are important interneurons in a simple orofacial reflex circuit consisting of a sensory neuron, interneuron and motor neuron. Moreover, the somatotopy of primary afferent fibers from the head and neck confirms the "onion skin hypothesis" and suggests rostral cervical dermatomes blend seamlessly with "cranial dermatomes." The transition area between subnucleus interpolaris and subnucleus caudalis is addressed while the paratrigeminal nucleus is discussed as an interface between the somatic and visceral nervous systems. © 2017 Panneton, Pan and Gan.


Author Keywords
Facial motor nucleus;  Lamina v;  Onion skin theory;  Trigeminal;  Trigeminocervical complex


Document Type: Article
Source: Scopus

 

8) 

Shine, J.M., Kucyi, A., Foster, B.L., Bickel, S., Wang, D., Liu, H., Poldrack, R.A., Hsieh, L.-T., Hsiang, J.C., Parvizi, J.
Distinct patterns of temporal and directional connectivity among intrinsic networks in the human brain
(2017) Journal of Neuroscience, 37 (40), pp. 9667-9674. 

DOI: 10.1523/JNEUROSCI.1574-17.2017


a Laboratory of Behavioral and Cognitive Neuroscience, Stanford Human Intracranial Cognitive Electrophysiology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States
b Department of Psychology, Stanford University, Stanford, CA, United States
c Central Clinical School, The University of Sydney, Sydney, NSW, Australia
d Department of Neurosurgery, Baylor College of MedicineTX, United States
e Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
f Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
g Center for Neuroscience, University of California, Davis, CA, United States
h Washington University, St. Louis, MO, United States


Abstract
To determine the spatiotemporal relationships among intrinsic networks of the human brain, we recruited seven neurosurgical patients (four males and three females) who were implanted with intracranial depth electrodes. We first identified canonical resting-state networks at the individual subject level using an iterative matching procedure on each subject’s resting-state fMRI data.Wethen introduced single electrical pulses to fMRI pre-identified nodes of the default network (DN), frontoparietal network (FPN), and salience network (SN) while recording evoked responses in other recording sites within the same networks. We found bidirectional signal flow across the three networks, albeit with distinct patterns of evoked responses within different time windows. We used a data-driven clustering approach to show that stimulation of the FPN and SN evoked a rapid (<70 ms) response that was predominantly higher within the SN sites, whereas stimulation of the DN led to sustained responses in later time windows (85–200 ms). Stimulations in the medial temporal lobe components of the DN evoked relatively late effects (>130 ms) in other nodes of the DN, as well as FPN and SN. Our results provide temporal information about the patterns of signal flow between intrinsic networks that provide insights into the spatiotemporal dynamics that are likely to constrain the architecture of the brain networks supporting human cognition and behavior. © 2017 the authors.


Author Keywords
Default network;  Electrical evoked potentials;  Frontoparietal network;  Intracranial EEG;  Salience network


Document Type: Article
Source: Scopus

 

9) 

Searles Nielsen, S., Warden, M.N., Camacho-Soto, A., Willis, A.W., Wright, B.A., Racette, B.A.
A predictive model to identify Parkinson disease from administrative claims data
(2017) Neurology, . Article in Press. 

DOI: 10.1212/WNL.0000000000004536


From the Department of Neurology (S.S.N., M.N.W., A.C.-S., B.A.W., B.A.R.), Washington University School of Medicine, St. Louis, MO; Departments of Neurology and Biostatistics and Epidemiology (A.W.W.), University of Pennsylvania School of Medicine, Philadelphia; and School of Public Health, Faculty of Health Sciences (B.A.R.), University of the Witwatersrand, Parktown, South Africa.


Abstract
Objective: To use administrative medical claims data to identify patients with incident Parkinson disease (PD) prior to diagnosis. Methods: Using a population-based case-control study of incident PD in 2009 among Medicare beneficiaries aged 66–90 years (89,790 cases, 118,095 controls) and the elastic net algorithm, we developed a cross-validated model for predicting PD using only demographic data and 2004–2009 Medicare claims data. We then compared this model to more basic models containing only demographic data and diagnosis codes for constipation, taste/smell disturbance, and REM sleep behavior disorder, using each model's receiver operator characteristic area under the curve (AUC). Results: We observed all established associations between PD and age, sex, race/ethnicity, tobacco smoking, and the above medical conditions. A model with those predictors had an AUC of only 0.670 (95% confidence interval [CI] 0.668–0.673). In contrast, the AUC for a predictive model with 536 diagnosis and procedure codes was 0.857 (95% CI 0.855–0.859). At the optimal cut point, sensitivity was 73.5% and specificity was 83.2%. Conclusions: Using only demographic data and selected diagnosis and procedure codes readily available in administrative claims data, it is possible to identify individuals with a high probability of eventually being diagnosed with PD. © 2017 American Academy of Neurology


Document Type: Article in Press
Source: Scopus

 

10) 

Gallardo, G., Holtzman, D.M.
Antibody therapeutics targeting Aβ and tau
(2017) Cold Spring Harbor Perspectives in Medicine, 7 (10), art. no. a024331, . 

DOI: 10.1101/cshperspect.a024331


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


Abstract
The astonishing findings that active and passive immunization against amyloid-b (Aβ) in mouse models of Alzheimer’s disease (AD) dramatically decreased amyloid burden led to a rapid initiation of human clinical trials with much enthusiasm. However, methodological issues and adverse effects relating to these clinical trials arose, challenging the effectiveness and safety of these reagents. Efforts are now underway to develop safer immunotherapeutic approaches toward Aβ and the treatment of individuals at risk for AD before or in the earliest stages of cognitive decline with new hopes. Furthermore, several studies have shown tau as a potential immunotherapeutic target for the treatment of tauopathy-related diseases including frontotemporal lobar dementia (FTLD). Both active and passive immunization targeting tau in mouse models of tauopathy effectively decreased tau pathology while improving cognitive performance. These preclinical studies have highlighted tau as an alternative target with much anticipation of clinical trials to be undertaken. © 2017 Cold Spring Harbor Laboratory Press. All rights reserved.


Document Type: Article
Source: Scopus

 

11) 

Appachi, S., Specht, J.L., Raol, N., Lieu, J.E.C., Cohen, M.S., Dedhia, K., Anne, S.
Auditory Outcomes with Hearing Rehabilitation in Children with Unilateral Hearing Loss: A Systematic Review
(2017) Otolaryngology - Head and Neck Surgery (United States), 157 (4), pp. 565-571. 

DOI: 10.1177/0194599817726757


a Cleveland Clinic, Cleveland, OH, United States
b Department of Otolaryngology–Head and Neck Surgery, Emory University School of Medicine, Atlanta, GA, United States
c Department of Otolaryngology–Head and Neck Surgery, Washington University, St Louis, MO, United States
d Department of Otolaryngology, Harvard Medical School, Boston, MA, United States


Abstract
Objective: Options for management of unilateral hearing loss (UHL) in children include conventional hearing aids, bone-conduction hearing devices, contralateral routing of signal (CROS) aids, and frequency-modulating (FM) systems. The objective of this study was to systematically review the current literature to characterize auditory outcomes of hearing rehabilitation options in UHL. Data Sources: PubMed, EMBASE, Medline, CINAHL, and Cochrane Library were searched from inception to January 2016. Manual searches of bibliographies were also performed. Review Methods: Studies analyzing auditory outcomes of hearing amplification in children with UHL were included. Outcome measures included functional and objective auditory results. Two independent reviewers evaluated each abstract and article. Results: Of the 249 articles identified, 12 met inclusion criteria. Seven articles solely focused on outcomes with bone-conduction hearing devices. Outcomes favored improved pure-tone averages, speech recognition thresholds, and sound localization in implanted patients. Five studies focused on FM systems, conventional hearing aids, or CROS hearing aids. Limited data are available but suggest a trend toward improvement in speech perception with hearing aids. FM systems were shown to have the most benefit for speech recognition in noise. Studies evaluating CROS hearing aids demonstrated variable outcomes. Conclusions: Data evaluating functional and objective auditory measures following hearing amplification in children with UHL are limited. Most studies do suggest improvement in speech perception, speech recognition in noise, and sound localization with a hearing rehabilitation device. © 2017, © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2017.


Author Keywords
hearing loss;  hearing rehabilitation;  unilateral


Document Type: Review
Source: Scopus

 

12) 

Anne, S., Lieu, J.E.C., Cohen, M.S.
Speech and Language Consequences of Unilateral Hearing Loss: A Systematic Review
(2017) Otolaryngology - Head and Neck Surgery (United States), 157 (4), pp. 572-579. 

DOI: 10.1177/0194599817726326


a Department of Otolaryngology–Head and Neck Surgery, Cleveland Clinic, Cleveland, OH, United States
b Department of Otolaryngology–Head and Neck Surgery, Washington University, St Louis, MO, United States
c Department of Otolaryngology, Harvard Medical School, Boston, MA, United States


Abstract
Objective: Unilateral hearing loss has been shown to have negative consequences for speech and language development in children. The objective of this study was to systematically review the current literature to quantify the impact of unilateral hearing loss on children, with the use of objective measures of speech and language. Data Sources: PubMed, EMBASE, Medline, CINAHL, and Cochrane Library were searched from inception to March 2015. Manual searches of references were also completed. Review Methods: All studies that described speech and language outcomes for children with unilateral hearing loss were included. Outcome measures included results from any test of speech and language that evaluated or had age-standardized norms. Due to heterogeneity of the data, quantitative analysis could not be completed. Qualitative analysis was performed on the included studies. Two independent evaluators reviewed each abstract and article. Results: A total of 429 studies were identified; 13 met inclusion criteria and were reviewed. Overall, 7 studies showed poorer scores on various speech and language tests, with effects more pronounced for children with severe to profound hearing loss. Four studies did not demonstrate any difference in testing results between patients with unilateral hearing loss and those with normal hearing. Two studies that evaluated effects on speech and language longitudinally showed initial speech problems, with improvement in scores over time. Conclusions: There are inconsistent data regarding effects of unilateral hearing loss on speech and language outcomes for children. The majority of recent studies suggest poorer speech and language testing results, especially for patients with severe to profound unilateral hearing loss. © 2017, © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2017.


Author Keywords
hearing loss;  speech delay;  unilateral


Document Type: Review
Source: Scopus

 

13) 

Roland, J.L., Price, R.L., Kamath, A.A., Hassan Akbari, S., Leuthardt, E.C., Miller, B.A., Smyth, M.D.
Hydrocephalus presenting as idiopathic aqueductal stenosis with subsequent development of obstructive tumor: Report of 2 cases demonstrating the importance of serial imaging
(2017) Journal of Neurosurgery: Pediatrics, 20 (4), pp. 329-333. 

DOI: 10.3171/2017.5.PEDS1779


a Department of Neurological Surgery, Washington University School of Medicine in St. Louis, Campus-Box 8057, 660 South Euclid Ave., St. Louis, MO, United States
b Department of Neuroscience, United States
c Department of Biomedical Engineering, United States
d Department of Mechanical Engineering and Materials Science, United States
e Center for Innovation in Neuroscience and Technology, United States
f Brain Laser Center, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The authors describe 2 cases of triventricular hydrocephalus initially presenting as aqueductal stenosis that subsequently developed tumors of the pineal and tectal region. The frst case resembled late-onset idiopathic aqueductal stenosis on serial imaging. Subsequent imaging revealed a new tumor in the pineal region causing mass effect on the midbrain. The second case presented in a more typical pattern of aqueductal stenosis during infancy. On delayed follow-up imaging, an enlarging tectal mass was discovered. In both cases hydrocephalus was successfully treated by cerebrospinal?uid diversion prior to tumor presentation. The differential diagnoses, diagnostic testing, and treatment course for these unusual cases are discussed. The importance of follow-up MRI in cases of idiopathic aqueductal stenosis is emphasized by these exemplar cases. © 2017 AANS.


Author Keywords
Aqueductal stenosis;  Germ cell tumor;  Hydrocephalus;  Pineal region;  Tectal glioma


Document Type: Article
Source: Scopus

 

14) 

Rehker, J., Rodhe, J., Nesbitt, R.R., Boyle, E.A., Martin, B.K., Lord, J., Karaca, I., Naj, A., Jessen, F., Helisalmi, S., Soininen, H., Hiltunen, M., Ramirez, A., Scherer, M., Farrer, L.A., Haines, J.L., Pericak-Vance, M.A., Raskind, W.H., Cruchaga, C., Schellenberg, G.D., Joseph, B., Brkanac, Z.
Caspase-8, association with Alzheimer’s Disease and functional analysis of rare variants
(2017) PLoS ONE, 12 (10), art. no. e0185777, . 

DOI: 10.1371/journal.pone.0185777


a Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States
b Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden
c Department of Genetics, Stanford UniversityCA, United States
d Department of Genome Sciences, University of Washington, Seattle, WA, United States
e Department of Psychiatry, Washington University, St. Louis, MO, United States
f Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
g Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
h Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany
i German Center for Neurodegenerative Diseases, Bonn, Germany
j Institute of Clinical Medicine–Neurology, University of Eastern Finland, Kuopio, Finland
k Department of Neurology, Kuopio University Hospital, Kuopio, Finland
l Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
m Institute of Human Genetics, University of Bonn, Bonn, Germany
n Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
o Departments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Epidemiology, and Biostatistics, Boston University, Boston, MA, United States
p Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, United States
q Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, United States
r John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, United States
s Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, FL, United States
t Department of Medicine, University of Washington, Seattle, WA, United States
u Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States


Abstract
The accumulation of amyloid beta (Aβ) peptide (Amyloid cascade hypothesis), an APP protein cleavage product, is a leading hypothesis in the etiology of Alzheimer’s disease (AD). In order to identify additional AD risk genes, we performed targeted sequencing and rare variant burden association study for nine candidate genes involved in the amyloid metabolism in 1886 AD cases and 1700 controls. We identified a significant variant burden association for the gene encoding caspase-8, CASP8 (p = 8.6x10-5). For two CASP8 variants, p.K148R and p. I298V, the association remained significant in a combined sample of 10,820 cases and 8,881 controls. For both variants we performed bioinformatics structural, expression and enzymatic activity studies and obtained evidence for loss of function effects. In addition to their role in amyloid processing, caspase-8 and its downstream effector caspase-3 are involved in synaptic plasticity, learning, memory and control of microglia pro-inflammatory activation and associated neurotoxicity, indicating additional mechanisms that might contribute to AD. As caspase inhibition has been proposed as a mechanism for AD treatment, our finding that AD-associated CASP8 variants reduce caspase function calls for caution and is an impetus for further studies on the role of caspases in AD and other neurodegenerative diseases. © 2017 Rehker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Document Type: Article
Source: Scopus

 

15) 

Lee, A.A., Poddar, N., Hammami, M.B., Veerapong, J., Cao, D., Lai, J.-P.
Gastric spindle cell neuroendocrine tumor mimicking gastrointestinal stromal tumor: Unique morphology and diagnostic pitfall
(2017) Anticancer Research, 37 (10), pp. 5893-5897. 

DOI: 10.21873/anticanres.12035


a Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO, United States
b Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, United States
c Department of Surgery, Saint Louis University School of Medicine, St. Louis, MO, United States
d Department of Pathology and Immunology, Washington University, St. Louis, MO, United States
e Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States


Abstract
Gastric neuroendocrine tumors (GNETs) with spindle cell morphology are extremely rare. We present a case of a 49-year-old female patient with a history of systemic lupus erythematosus, Sjogren's syndrome, and gastroesophageal reflux disease. She was initially thought to have a spindle cell gastrointestinal stromal tumor per histological studies of the fundic polypectomy samples. Immunohistochemically, the tumor cells were negative for CD117, and CD34, but positive for chromogranin, synaptophysin, and CD56 with a 6% Ki-67 index, consistent with a spindle cell-type well differentiated neuroendocrine tumor, World Health Organization (WHO) Grade 2. To the best of our knowledge, this is the first case report of a gastric spindle cell neuroendocrine tumor in the English literature.


Author Keywords
Gastric neuroendocrine tumor;  Gastrointestinal stromal tumor;  Immunohistochemistry;  Spindle cell


Document Type: Article
Source: Scopus

 

16) 

Miller, B.A., Salehi, A., Limbrick, D.D., Smyth, M.D.
Applications of a robotic stereotactic arm for pediatric epilepsy and neurooncology surgery
(2017) Journal of Neurosurgery: Pediatrics, 20 (4), pp. 364-370. 

DOI: 10.3171/2017.5.PEDS1782


Department of Neurosurgery, Washington University School of Medicine, One Children's Pl., Ste. 4s20, St. Louis, MO, United States


Abstract
OBJECTIVE The ROSA device is a robotic stereotactic arm that uses a laser system to register the patient's head or spine with MR or CT images. In this study, the authors analyze their experience with this system in pediatric neurosurgical applications and present selected cases that exemplify the usefulness of this system. METHODS The authors reviewed all cases that utilized the ROSA system at their institution. Patient demographics, pathology, complications, electrode placement, laser ablation, and biopsy accuracy were analyzed. Patient disposition and condition at follow-up were also analyzed. RESULTS Seventeen patients underwent 23 procedures using the ROSA system. A total of 87 electroencephalography electrodes were placed, with 13% deviating more than 3 mm from target. Six patients underwent stereotactic needle biopsy, and 9 underwent laser interstitial thermotherapy (LITT). One patient who underwent LITT required a subsequent craniotomy for tumor resection. Another patient experienced an asymptomatic extraaxial hematoma that spontaneously resolved. No patient suffered neurological complications during follow-up. Follow-up from the last procedure averaged 180 days in epilepsy patients and 309 days in oncology patients. CONCLUSIONS The precision, ease of use, and versatility of the ROSA system make it well suited for pediatric neurosurgical practice. Further work, including long-term analysis of results and cost-effectiveness, will help determine the utility of this system and if its applications can be expanded. © 2017 AANS.


Author Keywords
Depth electrodes;  Epilepsy;  Laser ablation;  Robotic neurosurgery;  Stereo-EEG;  Surgical technique


Document Type: Article
Source: Scopus

 

17) 

Capotosto, P., Baldassarre, A., Sestieri, C., Spadone, S., Romani, G.L., Corbetta, M.
Task and Regions Specific Top-Down Modulation of Alpha Rhythms in Parietal Cortex
(2017) Cerebral Cortex, 27 (10), pp. 4815-4822. 

DOI: 10.1093/cercor/bhw278


a Department of Neuroscience Imaging, and Clinical Science, Institute of Advanced Biomedical Technologies (ITAB), University G. d'Annunzio, Via dei Vestini 33, Chieti, Italy
b Department of Neurology Radiology, Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Alpha (8-12 Hz) power desynchronization is strongly associated to visual perception but has been observed in a large variety of tasks, indicating a general role in task anticipation. We previously reported in human observers that interference by repetitive transcranial magnetic stimulation (rTMS) of core regions of the dorsal attention network (DAN) disrupts both anticipatory alpha desynchronization and performance during a visuospatial attention (VSA) task. Here, we test the hypothesis that alpha desynchronization is task specific, and can be selectively modulated by interfering with activity in different higher-order parietal regions. We contrast the effects of rTMS on alpha rhythms and behavior on 2 different tasks: a VSA and a semantic decision task, by targeting the posterior intraparietal sulcus (pIPS), a core region of the DAN, or the angular gyrus (AG), a core region of the default mode network (DMN). We found that both performance and anticipatory alpha desynchronization were affected by stimulation of IPS only during VSA, and of AG only during semantic decisions. These findings indicate the existence of multiple dedicated parietal channels for the modulation of anticipatory alpha rhythms, which in turn reflect task-specific modulation of excitability in human parieto-occipital cortex. © The Author 2016. Published by Oxford University Press. All rights reserved.


Author Keywords
anticipatory alpha;  parietal cortex;  rTMS;  semantic decision;  visuospatial attention


Document Type: Article
Source: Scopus

 

18) 

Li, G., Mayer, C.L., Morelli, D., Millard, S.P., Raskind, W.H., Petrie, E.C., Cherrier, M., Fagan, A.M., Raskind, M.A., Peskind, E.R.
Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults
(2017) Neurology, 89 (12), pp. 1251-1255. 

DOI: 10.1212/WNL.0000000000004392


From the Geriatric Research, Education, and Clinical Center (G.L., W.H.R.) and Northwest Network (VISN-20) Mental Illness, Research, Education, and Clinical Center (G.L., C.L.M., D.M., S.P.M., E.C.P., M.A.R., E.R.P.), Veterans Affairs Puget Sound Health Care System; Departments of Psychiatry and Behavioral Sciences (G.L., E.C.P., M.C., M.A.R., E.R.P.) and Medicine (W.H.R.), University of Washington, Seattle; and Department of Neurology (A.M.F.), Washington University in St. Louis, MO


Abstract
OBJECTIVE: To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure.

METHODS: Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group). Simvastatin was titrated to 40 mg/d. CSF Aβ42, total tau, and p-tau181 were measured at baseline and after 12 months of treatment using the INNO-BIA AlzBio3 assay. We used analysis of covariance to assess differences in biomarker change from baseline between treatment groups, adjusting for age, sex, and APOE ε4 status.

RESULTS: Changes from baseline did not differ significantly between treatment groups for any CSF biomarker, with p values of 0.53, 0.36, and 0.25 for CSF Aβ42, total tau, and p-tau181, respectively. There was no significant modifying effect of sex, APOE ε4, or baseline high-density lipoprotein or triglycerides on treatment group for any of the biomarkers (all p > 0.18). However, a significant interaction between treatment group and baseline low-density lipoprotein (LDL) was observed for p-tau181 (p = 0.003), where greater decreases from baseline in CSF p-tau181 concentrations were associated with higher baseline LDL level for the simvastatin group.

CONCLUSIONS: Simvastatin-related reductions in CSF p-tau181 concentrations may be modulated by LDL cholesterol. The potential disease-modifying effects of simvastatin on CSF phospho-tau should be further investigated in persons with hypercholesterolemia. © 2017 American Academy of Neurology.


Document Type: Article
Source: Scopus

 

19) 

Abernathy, D.G., Kim, W.K., McCoy, M.J., Lake, A.M., Ouwenga, R., Lee, S.W., Xing, X., Li, D., Lee, H.J., Heuckeroth, R.O., Dougherty, J.D., Wang, T., Yoo, A.S.
MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts
(2017) Cell Stem Cell, 21 (3), pp. 332-348.e9. 

DOI: 10.1016/j.stem.2017.08.002


a Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
b Program in Developmental, Regenerative, Stem Cell Biology, Washington University School of Medicine, St. Louis, MO, United States
c Program in Molecular Genetics & Genomics, Washington University School of Medicine, St. Louis, MO, United States
d Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, United States


Abstract
Directed reprogramming of human fibroblasts into fully differentiated neurons requires massive changes in epigenetic and transcriptional states. Induction of a chromatin environment permissive for acquiring neuronal subtype identity is therefore a major barrier to fate conversion. Here we show that the brain-enriched miRNAs miR-9/9 and miR-124 (miR-9/9-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. miR-9/9-124-induced neurons (miNs) are functionally excitable and uncommitted toward specific subtypes but possess open chromatin at neuronal subtype-specific loci, suggesting that such identity can be imparted by additional lineage-specific transcription factors. Consistently, we show that ISL1 and LHX3 selectively drive conversion to a highly homogeneous population of human spinal cord motor neurons. This study shows that modular synergism between miRNAs and neuronal subtype-specific transcription factors can drive lineage-specific neuronal reprogramming, providing a general platform for high-efficiency generation of distinct subtypes of human neurons. Abernathy et al. show that widespread epigenetic changes underlie miRNA-mediated direct reprogramming of primary adult human fibroblasts into neurons, revealing modular synergism between miRNAs and transcription factors to allow lineage-specific neuronal reprogramming. This work provides a platform for generating distinct subtypes of human neurons from patients. © 2017 Elsevier Inc.


Author Keywords
cell fate;  chromatin accessibility;  chromatin remodeling;  direct reprogramming;  DNA methylation;  epigenetics;  human neurons;  microRNA;  motor neurons;  neurogenesis


Document Type: Article
Source: Scopus

 

20) 

Tackett, J.L., Lilienfeld, S.O., Patrick, C.J., Johnson, S.L., Krueger, R.F., Miller, J.D., Oltmanns, T.F., Shrout, P.E.
It’s Time to Broaden the Replicability Conversation: Thoughts for and From Clinical Psychological Science
(2017) Perspectives on Psychological Science, 12 (5), pp. 742-756. 

DOI: 10.1177/1745691617690042


a Northwestern University, United States
b Emory University, United States
c Florida State University, United States
d University of California, Berkeley, United States
e University of Minnesota, United States
f University of Georgia, United States
g Washington University in St. Louis, United States
h New York University, United States


Abstract
Psychology is in the early stages of examining a crisis of replicability stemming from several high-profile failures to replicate studies in experimental psychology. This important conversation has largely been focused on social psychology, with some active participation from cognitive psychology. Nevertheless, several other major domains of psychological science—including clinical science—have remained insulated from this discussion. The goals of this article are to (a) examine why clinical psychology and allied fields, such as counseling and school psychology, have not been central participants in the replicability conversation; (b) review concerns and recommendations that are less (or more) applicable to or appropriate for research in clinical psychology and allied fields; and (c) generate take-home messages for scholars and consumers of the literature in clinical psychology and allied fields, as well as reviewers, editors, and colleagues from other areas of psychological science. © 2017, © The Author(s) 2017.


Author Keywords
assessment;  diagnosis;  disorders;  scientific methodology


Document Type: Article
Source: Scopus

 

21) 

Colclough, G.L., Smith, S.M., Nichols, T.E., Winkler, A.M., Sotiropoulos, S.N., Glasser, M.F., Van Essen, D.C., Woolrich, M.W.
The heritability of multi-modal connectivity in human brain activity
(2017) eLife, 6, art. no. e20178, . 

DOI: 10.7554/eLife.20178


a Oxford Centre for Human Brain Activity (OHBA), Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry University of Oxford, Oxford, United Kingdom
b Oxford Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences University of Oxford, Oxford, United Kingdom
c Department of Engineering Science, University of Oxford, Oxford, United Kingdom
d Department of Statistics, University of Warwick, Coventry, United Kingdom
e Warwick Manufacturing Group, International Manufacturing Centre, University of Warwick, Coventry, United Kingdom
f Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom
g School of Medicine, Washington University, St. Louis, United States


Abstract
Patterns of intrinsic human brain activity exhibit a profile of functional connectivity that is associated with behaviour and cognitive performance, and deteriorates with disease. This paper investigates the relative importance of genetic factors and the common environment between twins in determining this functional connectivity profile. Using functional magnetic resonance imaging (fMRI) on 820 subjects from the Human Connectome Project, and magnetoencephalographic (MEG) recordings from a subset, the heritability of connectivity among 39 cortical regions was estimated. On average over all connections, genes account for about 15% of the observed variance in fMRI connectivity (and about 10% in alpha-band and 20% in beta-band oscillatory power synchronisation), which substantially exceeds the contribution from the environment shared between twins. Therefore, insofar as twins share a common upbringing, it appears that genes, rather than the developmental environment, have the dominant role in determining the coupling of neuronal activity. © Colclough et al.


Document Type: Article
Source: Scopus

 

22) 

Acharya, S., Mahmood, M., Mullen, D., Yang, D., Tsien, C.I., Huang, J., Perkins, S.M., Rich, K., Chicoine, M., Leuthardt, E., Dowling, J., Dunn, G., Keller, J., Robinson, C.G., Abraham, C.
Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents
(2017) Advances in Radiation Oncology, . Article in Press. 

DOI: 10.1016/j.adro.2017.07.003


a Department of Radiation Oncology, Washington University, St. Louis, Missouri
b Department of Neurosurgery, Washington University, St. Louis, Missouri
c Department of Medical Oncology, Washington University, St. Louis, Missouri


Abstract
Purpose: Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials: Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results: A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively (P < .001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS + IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; P = .003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P = .001).One-year local control for SRS, SRS + IMT, and SRS + targeted therapy was 66%, 85%, and 72%, respectively (P = .044). On multivariate analysis, after adjusting for dose, SRS + IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P = .04). Conclusions: SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result. © 2017 The Authors.


Document Type: Article in Press
Source: Scopus

 

23) 

Wu, M., Guan, J., Li, C., Gunter, S., Nusrat, L., Ng, S., Dhand, K., Morshead, C., Kim, A., Das, S.
Aberrantly activated Cox-2 and Wnt signaling interact to maintain cancer stem cells in glioblastoma
(2017) Oncotarget, 8 (47), pp. 82217-82230. 

DOI: 10.18632/oncotarget.19283


a Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for SickKids, University of Toronto, Toronto, Canada
b Department of Neurosurgery and Cell Biology, Washington University, St. Louis, MO, United States
c McLaughlin Centre for Molecular Medicine, University of Toronto, Toronto, Canada
d Division of Neurosurgery and Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Canada


Abstract
Glioblastoma recurrence after aggressive therapy typically occurs within six months, and patients inevitably succumb to their disease. Tumor recurrence is driven by a subpopulation of cancer stem cells in glioblastoma (glioblastoma stem-like cells, GSCs), which exhibit resistance to cytotoxic therapies, compared to their non-stem-cell counterparts. Here, we show that the Cox-2 and Wnt signaling pathways are aberrantly activated in GSCs and interact to maintain the cancer stem cell identity. Cox-2 stimulates GSC self-renewal and proliferation through prostaglandin E2 (PGE2), which in turn activates the Wnt signaling pathway. Wnt signaling underlies PGE2-induced GSC selfrenewal and independently directs GSC self-renewal and proliferation. Inhibition of PGE2 enhances the effect of temozolomide on GSCs, but affords only a modest survival advantage in a xenograft model in the setting of COX-independent Wnt activation. Our findings uncover an aberrant positive feedback interaction between the Cox-2/PGE2 and Wnt pathways that mediates the stem-like state in glioblastoma. © Wu et al.


Author Keywords
Cancer stem cells;  Cyclooxygenase;  Glioblastoma;  Prostaglandin E2;  Wnt


Document Type: Article
Source: Scopus

 

24) 

Black, K.J.
Tourette syndrome research highlights from 2016
(2017) F1000Research, 6, art. no. 1430, . 

DOI: 10.12688/f1000research.12330.1


Departments of Psychiatry, Neurology, Radiology, and Neuroscience, Washington University School of Medicine, St. Louis, MO, United States


Abstract
This article presents highlights chosen from research that appeared during 2016 on Tourette syndrome and other tic disorders. Selected articles felt to represent meaningful advances in the field are briefly summarized. © 2017 Black KJ.


Author Keywords
Animal models;  Genetics;  Pathophysiology;  Premonitory;  Review;  Therapy;  Tic disorders;  Tourette syndrome


Document Type: Review
Source: Scopus

 

25) 

de Pasquale, F., Corbetta, M., Betti, V., Della Penna, S.
Cortical cores in network dynamics
(2017) NeuroImage, . Article in Press. 

DOI: 10.1016/j.neuroimage.2017.09.063


a Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy
b Department of Neuroscience, University of Padua, Padua 35128, Italy
c Departments of Neurology, Radiology, Neuroscience, and Biomedical Engineering, Washington University, St. Louis, MO 63101 USA
d Department of Psychology, University of Rome La Sapienza, 00185, Rome, Italy
e Fondazione Santa Lucia, Istituto Di Ricovero e Cura a Carattere Scientifico, 00142, Rome, Italy
f Institute for Advanced Biomedical Technologies and Department of Neuroscience, Imaging and Clinical Sciences, G. D'Annunzio University, Chieti, Italy


Abstract
Spontaneous brain activity at rest is spatially and temporally organized in networks of cortical and subcortical regions specialized for different functional domains. Even though brain networks were first studied individually through functional Magnetic Resonance Imaging, more recent studies focused on their dynamic 'integration'. Integration depends on two fundamental properties: the structural topology of brain networks and the dynamics of functional connectivity. In this scenario, cortical hub regions, that are central regions highly connected with other areas of the brain, play a fundamental role in serving as way stations for network traffic. In this review, we focus on the functional organization of a set of hub areas that we define as the 'dynamic core'. In the resting state, these regions dynamically interact with other regions of the brain linking multiple networks. First, we introduce and compare the statistical measures used for detecting hubs. Second, we discuss their identification based on different methods (functional Magnetic Resonance Imaging, Diffusion Weighted Imaging, Electro/Magneto Encephalography). Third, we show that the degree of interaction between these core regions and the rest of the brain varies over time, indicating that their centrality is not stationary. Moreover, alternating periods of strong and weak centrality of the core relate to periods of strong and weak global efficiency in the brain. These results indicate that information processing in the brain is not stable, but fluctuates and its temporal and spectral properties are discussed. In particular, the hypothesis of '. pulsed' information processing, discovered in the slow temporal scale, is explored for signals at higher temporal resolution. © 2017 Elsevier Inc.


Document Type: Article in Press
Source: Scopus

October 16, 2017

Kafashan, M., Palanca, B.J.A., Ching, S.
Dimensionality reduction impedes the extraction of dynamic functional connectivity states from fMRI recordings of resting wakefulness
(2018) Journal of Neuroscience Methods, 293, pp. 151-161. 

DOI: 10.1016/j.jneumeth.2017.09.013


a Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Department of Neurobiology, Harvard Medical School, Boston, MA, United States
c Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
d Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Background Resting wakefulness is not a unitary state, with evidence accumulating that spontaneous reorganization of brain activity can be assayed through functional magnetic resonance imaging (fMRI). The dynamics of correlated fMRI signals among functionally-related brain regions, termed dynamic functional connectivity (dFC), may represent nonstationarity arising from underlying neural processes. However, given the dimensionality and noise inherent in such recordings, seeming fluctuations in dFC could be due to sampling variability or artifacts. New method Here, we highlight key methodological considerations when evaluating dFC in resting-state fMRI data. Comparison with existing method In particular, we demonstrate how dimensionality reduction of fMRI data, a common practice often involving principal component analysis, may give rise to spurious dFC phenomenology due to its effect of decorrelating the underlying time-series. Conclusion We formalize a dFC assessment that avoids dimensionality reduction and use it to show the existence of at least two FC states in the resting-state. © 2017 Elsevier B.V.


Author Keywords
Dynamic functional connectivity (dFC);  FC state analysis;  Resting-state functional magnetic resonance;  Spatiotemporal analysis


Document Type: Article
Source: Scopus

 

2) 

Gross, J.H., Bertrand, M., Hirose, K.
Benign Rolandic epilepsy presenting like paradoxical vocal fold motion
(2017) International Journal of Pediatric Otorhinolaryngology, 102, pp. 154-156. 

DOI: 10.1016/j.ijporl.2017.09.021


a Washington University School of Medicine, Department of Otolaryngology, 660 South Euclid Avenue, Saint Louis, Missouri, United States
b Washington University School of Medicine, Department of Neurology, 660 South Euclid Avenue, Saint Louis, Missouri, United States


Abstract
Paradoxical vocal fold motion (PVFM) is characterized by vocal fold adduction during respiration. Benign Rolandic epilepsy (BRE) is the most common childhood epilepsy and can cause oropharyngolaryngeal or facial manifestations. A 9-year-old male presented with intermittent apnea lasting 30–60 seconds and presumed PVFM. The patient's physical and fiberoptic exam were normal. He was admitted and found to have episodes of oxygen desaturation, neck twitching, and tongue burning. An EEG revealed focal epilepsy. After starting anti-epileptic medications, he had resolution of symptoms. Our patient was eventually diagnosed with BRE, a focal onset epilepsy that can mimic primary otolaryngologic disease. © 2017 Elsevier B.V.


Author Keywords
Apnea;  Children;  Epilepsy;  Laryngeal spasm;  Paradoxical vocal fold motion


Document Type: Article
Source: Scopus

 

3) 

Joksimovic, S.M., Eggan, P., Izumi, Y., Joksimovic, S.L., Tesic, V., Dietz, R.M., Orfila, J.E., DiGruccio, M.R., Herson, P.S., Jevtovic-Todorovic, V., Zorumski, C.F., Todorovic, S.M.
The role of T-type calcium channels in the subiculum: to burst or not to burst?
(2017) Journal of Physiology, 595 (19), pp. 6327-6348. Cited 1 time.

DOI: 10.1113/JP274565


a Department of Anesthesiology, University of Colorado, School of Medicine, Aurora, CO, United States
b Department of Psychiatry & Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St Louis, MO, United States
c Department of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, CA, United States


Abstract
Key points: Pharmacological, molecular and genetic data indicate a prominent role of low-voltage-activated T-type calcium channels (T-channels) in the firing activity of both pyramidal and inhibitory interneurons in the subiculum. Pharmacological inhibition of T-channels switched burst firing with lower depolarizing stimuli to regular spiking, and fully abolished hyperpolarization-induced burst firing. Our molecular studies showed that CaV3.1 is the most abundantly expressed isoform of T-channels in the rat subiculum. Consistent with this finding, both regular-spiking and burst firing patterns were profoundly depressed in the mouse with global deletion of CaV3.1 isoform of T-channels. Selective inhibition of T-channels and global deletion of CaV3.1 channels completely suppressed development of long-term potentiation (LTP) in the CA1–subiculum, but not in the CA3–CA1 pathway. Abstract: Several studies suggest that voltage-gated calcium currents are involved in generating high frequency burst firing in the subiculum, but the exact nature of these currents remains unknown. Here, we used selective pharmacology, molecular and genetic approaches to implicate Cav3.1-containing T-channels in subicular burst firing, in contrast to several previous reports discounting T-channels as major contributors to subicular neuron physiology. Furthermore, pharmacological antagonism of T-channels, as well as global deletion of CaV3.1 isoform, completely suppressed development of long-term potentiation (LTP) in the CA1–subiculum, but not in the CA3–CA1 pathway. Our results indicate that excitability and synaptic plasticity of subicular neurons relies heavily on T-channels. Hence, T-channels may be a promising new drug target for different cognitive deficits. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society


Author Keywords
calcium;  hippocampus;  low-threshold-activated


Document Type: Article
Source: Scopus

 

4) 

Rogers, C.E.
Here/In This Issue and There/Abstract Thinking: Does This Answer Your Question?
(2017) Journal of the American Academy of Child and Adolescent Psychiatry, 56 (10), pp. 801-802. 

DOI: 10.1016/j.jaac.2017.08.007


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


Document Type: Article
Source: Scopus

 

5) 

Sun, W., Marongelli, E.N., Watkins, P.V., Barbour, D.L.
Decoding sound level in the marmoset primary auditory cortex
(2017) Journal of Neurophysiology, 118 (4), pp. 2024-2033. 

DOI: 10.1152/jn.00670.2016


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


Abstract
Neurons that respond favorably to a particular sound level have been observed throughout the central auditory system, becoming steadily more common at higher processing areas. One theory about the role of these level-tuned or nonmonotonic neurons is the level-invariant encoding of sounds. To investigate this theory, we simulated various subpopulations of neurons by drawing from real primary auditory cortex (A1) neuron responses and surveyed their performance in forming different sound level representations. Pure nonmonotonic subpopulations did not provide the best level-invariant decoding; instead, mixtures of monotonic and nonmonotonic neurons provided the most accurate decoding. For level-fidelity decoding, the inclusion of nonmonotonic neurons slightly improved or did not change decoding accuracy until they constituted a high proportion. These results indicate that nonmonotonic neurons fill an encoding role complementary to, rather than alternate to, monotonic neurons. NEW & NOTEWORTHY Neurons with nonmonotonic rate-level functions are unique to the central auditory system. These level-tuned neurons have been proposed to account for invariant sound perception across sound levels. Through systematic simulations based on real neuron responses, this study shows that neuron populations perform sound encoding optimally when containing both monotonic and nonmonotonic neurons. The results indicate that instead of working independently, nonmonotonic neurons complement the function of monotonic neurons in different sound-encoding contexts. © 2017 the American Physiological Society.


Author Keywords
Auditory cortex;  Neural coding;  Nonmonotonic;  Primate;  Sound pressure level encoding


Document Type: Article
Source: Scopus

 

6) 

Wright, N.C., Wessel, R.
Network activity influences the subthreshold and spiking visual responses of pyramidal neurons in the three-layer turtle cortex
(2017) Journal of Neurophysiology, 118 (4), pp. 2142-2155. 

DOI: 10.1152/jn.00340.2017


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


Abstract
A primary goal of systems neuroscience is to understand cortical function, typically by studying spontaneous and stimulus-modulated cortical activity. Mounting evidence suggests a strong and complex relationship exists between the ongoing and stimulus-modulated cortical state. To date, most work in this area has been based on spiking in populations of neurons. While advantageous in many respects, this approach is limited in scope: it records the activity of a minority of neurons and gives no direct indication of the underlying subthreshold dynamics. Membrane potential recordings can fill these gaps in our understanding, but stable recordings are difficult to obtain in vivo. Here, we recorded subthreshold cortical visual responses in the ex vivo turtle eye-attached whole brain preparation, which is ideally suited for such a study. We found that, in the absence of visual stimulation, the network was “synchronous”; neurons displayed net-work-mediated transitions between hyperpolarized (Down) and depo-larized (Up) membrane potential states. The prevalence of these slow-wave transitions varied across turtles and recording sessions. Visual stimulation evoked similar Up states, which were on average larger and less reliable when the ongoing state was more synchronous. Responses were muted when immediately preceded by large, spontaneous Up states. Evoked spiking was sparse, highly variable across trials, and mediated by concerted synaptic inputs that were, in general, only very weakly correlated with inputs to nearby neurons. Together, these results highlight the multiplexed influence of the cortical network on the spontaneous and sensory-evoked activity of individual cortical neurons. NEW & NOTEWORTHY Most studies of cortical activity focus on spikes. Subthreshold membrane potential recordings can provide complementary insight, but stable recordings are difficult to obtain in vivo. Here, we recorded the membrane potentials of cortical neurons during ongoing and visually evoked activity. We observed a strong relationship between network and single-neuron evoked activity spanning multiple temporal scales. The membrane potential perspective of cortical dynamics thus highlights the influence of intrinsic network properties on visual processing. © 2017 the American Physiological Society.


Author Keywords
Cortex;  Membrane potential;  Network state;  Vision


Document Type: Article
Source: Scopus

 

7) 

Duncan, R.P., McNeely, M.E., Earhart, G.M.
Maximum Step Length Test Perfo                rmance in People with Parkinson Disease: A Cross-sectional Study
(2017) Journal of Neurologic Physical Therapy, 41 (4), pp. 215-221. 

DOI: 10.1097/NPT.0000000000000201


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


Abstract
Background and Purpose: The Maximum Step Length Test (MSLT), a measure of one's capacity to produce a large step, has been studied in older adults, but not in people with Parkinson disease (PD). We characterized performance and construct validity of the MSLT in PD. Methods: Forty participants (mean age: 65.12 ± 8.20 years; 45% female) with idiopathic PD completed the MSLT while "OFF" and "ON" anti-PD medication. Construct validity was investigated by examining relationships between MSLT and measures of motor performance. The following measures were collected: Mini-Balance Evaluation Systems Test (Mini-BESTest), Activities-specific Balance Confidence (ABC) scale, gait velocity, 6-minute walk test (6MWT), Movement Disorder Society-Unified Parkinson Disease Rating Scale subsection III (MDS-UPDRS III), and Timed Up and Go (TUG) test. A repeated-measures analysis of variance tested for main effects of medication and stepping direction and the interaction between the 2. Pearson or Spearman correlations were used to assess the relationships between MSLT and motor performance measures (α = 0.05). Results: Regardless of medication status, participants stepped further in the forward direction compared with the backward and lateral directions (P < 0.001). Participants increased MSLT performance when ON-medication compared with OFF-medication (P = 0.004). Regardless of medication status, MSLT was moderately to strongly related to Mini-BESTest, TUG, and 6MWT. Discussion and Conclusions: People with PD stepped furthest in the forward direction when performing the MSLT. Increased MSLT performance was observed in the ON-medication state compared with OFF-medication; however, the small increase may not be clinically meaningful. Given the relationships between the MSLT and the Mini-BESTest, 6MWT, and TUG, MSLT performance appears to be associated with balance and gait hypokinesia in people with PD. Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A186). © 2017 Academy of Neurologic Physical Therapy, APTA.


Author Keywords
balance;  gait;  human movement system;  outcome measure


Document Type: Conference Paper
Source: Scopus

 

8) 

Moore, A.M.
Commentary on Management of Atraumatic Posterior Interosseous Nerve Palsy
(2017) Journal of Hand Surgery, 42 (10), pp. 831-832. 

DOI: 10.1016/j.jhsa.2017.07.027


Chief of the Section of Hand Surgery, Program Director of the Hand Fellowship, Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, MO, United States


Document Type: Note
Source: Scopus

 

9) 

Blum, K., Badgaiyan, R.D., Dunston, G.M., Baron, D., Modestino, E.J., McLaughlin, T., Steinberg, B., Gold, M.S., Gondré-Lewis, M.C.
The DRD2 Taq1A A1 Allele May Magnify the Risk of Alzheimer’s in Aging African-Americans
(2017) Molecular Neurobiology, pp. 1-11. Article in Press. 

DOI: 10.1007/s12035-017-0758-1


a Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, United States
b Department of Psychiatry and Behavioral Sciences, Keck Medicine University of Southern California, Los Angeles, CA, United States
c Division of Applied Clinical Research & Education, Dominion Diagnostics, LLC, North Kingstown, RI, United States
d Department of Neurogenetics, Igene, LLC, Austin, TX, United States
e Division of Reward Deficiency Syndrome and Addiction Therapy, Nupathways, Inc., Innsbrook, MO, United States
f Department of Clinical Neurology, Path Foundation, New York, NY, United States
g Division of Neuroscience Based Addiction Therapy, The Shores Treatment & Recovery Center, Port Saint Lucie, FL, United States
h Eötvös Loránd University, Institute of Psychology, Budapest, Hungary
i Department of Psychiatry and Behavioral Health, Richmond University Medical Center, 355 Bard Avenue, Staten Island, NY, United States
j NeuroPsychoSocial Genomics Core, National Human Genome Center, Howard University, Washington, DC, United States
k Department of Psychology, Curry College, Milton, MA, United States
l Center for Psychiatric Medicine, North Andover, MA, United States
m Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
n Developmental Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, DC, United States
o Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC, United States


Abstract
Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys cognitive skills and the ability to perform the simplest tasks. More than 5 million Americans are afflicted with Alzheimer’s; a disorder which ranks third, just behind heart disease and cancer, as a cause of death for older people. With no real cure and in spite of enormous efforts worldwide, the disease remains a mystery in terms of treatment. Importantly, African-Americans are two times as likely as Whites to develop late-onset Alzheimer’s disease and less likely to receive timely diagnosis and treatment. Dopamine function is linked to normal cognition and memory and carriers of the DRD2 Taq1A A1 allele have significant loss of D2 receptor density in the brain. Recent research has shown that A1 carriers have worse memory performance during long-term memory (LTM) updating, compared to non-carriers or A2-carriers. A1carriers also show less blood oxygen level-dependent (BOLD) activation in the left caudate nucleus which is important for LTM updating. This latter effect was only seen in older adults, suggesting magnification of genetic effects on brain functioning in the elderly. Moreover, the frequency of the A1 allele is 0.40 in African-Americans, with an approximate prevalence of the DRD2 A1 allele in 50% of an African-American subset of individuals. This is higher than what is found in a non-screened American population (≤ 28%) for reward deficiency syndrome (RDS) behaviors. Based on DRD2 known genetic polymorphisms, we hypothesize that the DRD2 Taq1A A1 allele magnifies the risk of Alzheimer’s in aging African-Americans. Research linking this high risk for Alzheimer’s in the African-American population, with DRD2/ANKK1-TaqIA polymorphism and neurocognitive deficits related to LTM, could pave the way for novel, targeted pro-dopamine homeostatic treatment. © 2017 Springer Science+Business Media, LLC


Author Keywords
African Americans;  Alzheimer’s disease;  Dopamine;  DRD2 gene;  Early life stress;  Long-term memory (LTM);  Reward deficiency syndrome


Document Type: Article in Press
Source: Scopus

 

10) 

Morley, B.J., Dolan, D.F., Ohlemiller, K.K., Simmons, D.D.
Generation and characterization of α9 and α10 nicotinic acetylcholine receptor subunit knockout mice on a C57BL/6J background
(2017) Frontiers in Neuroscience, 11 (SEP), art. no. 516, . 

DOI: 10.3389/fnins.2017.00516


a Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE, United States
b Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, United States
c Department of Otolaryngology, Washington University, St. Louis, MO, United States
d Department of Biology, Baylor University, Waco, TX, United States


Abstract
We generated constitutive knockout mouse models for the α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits by derivation from conditional knockouts by breeding with CRE deleter mice. We then backcrossed them onto a C57BL/6J genetic background. In this manuscript, we report the generation of the strains and an auditory phenotypic characterization of the constitutive α9 and α10 knockouts and a double α9α10 constitutive knockout. Although the α9 and α10 nAChR subunits are relevant to a number of physiological measures, we chose to characterize the mouse with auditory studies to compare them to existing but different α9 and α10 nAChR knockouts (KOs). Auditory brainstem response (ABR) measurements and distortion product otoacoustic emissions (DPOAEs) showed that all constitutive mouse strains had normal hearing. DPOAEs with contralateral noise (efferent adaptation measurements), however, showed that efferent strength was significantly reduced after deletion of both the α9 and α10 subunits, in comparison to wildtype controls. Animals tested were 3-8 weeks of age and efferent strength was not correlated with age. Confocal studies of single and double constitutive KOs showed that all KOs had abnormal efferent innervation of cochlear hair cells. The morphological results are similar to those obtained in other strains using constitutive deletion of exon 4 of α9 or α10 nAChR. The results of our physiological studies, however, differ from previous auditory studies using a α9 KO generated by deletion of the exon 4 region and backcrossed onto a mixed CBA/CaJ X 129Sv background. © 2017 Morley, Dolan, Ohlemiller and Simmons.


Author Keywords
Auditory brainstem response;  Distortion product otoacoustic emissions;  Efferent strength;  Nicotinic acetylcholine receptor


Document Type: Article
Source: Scopus

 

11) 

Klein, R.S.
Dual Blades: The Role of Musashi 1 in Zika Replication and Microcephaly
(2017) Cell Host and Microbe, 22 (1), pp. 9-11. 

DOI: 10.1016/j.chom.2017.06.015


a Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine, St Louis, MO, United States


Abstract
Infection with Zika virus (ZIKV) during pregnancy may cause severe developmental defects in the human brain via unknown mechanisms. In a recent issue of Science, Chavali et al. (2017) identified a neural progenitor cell (NPC)-specific RNA binding protein that may underlie the high levels of ZIKV replication and apoptosis observed in these cells during congenital infections. Infection with Zika virus (ZIKV) during pregnancy may cause severe developmental defects in the human brain via unknown mechanisms. In a recent issue of Science, Chavali et al. (2017) identified a neural progenitor cell (NPC)-specific RNA binding protein that may underlie the high levels of ZIKV replication and apoptosis observed in these cells during congenital infections. © 2017 Elsevier Inc.


Document Type: Short Survey
Source: Scopus

 

12) 

Ren, L., Chang, M.J., Zhang, Z., Dhaka, A., Guo, Z., Cao, Y.-Q.
Quantitative Analysis of Mouse Dural Afferent Neurons Expressing TRPM8, VGLUT3, and NF200
(2017) Headache, . Article in Press. 

DOI: 10.1111/head.13188


a Washington University Pain Center and Department of Anesthesiology, Washington University School of MedicineSt. Louis, MO USA
b Department of Biological Structure, Neurobiology and Behavior Graduate ProgramUniversity of WashingtonSeattle, WA USA


Abstract
Objective: To quantify the abundance of dural afferent neurons expressing transient receptor potential channel melastatin 8 (TRPM8), vesicular glutamate transporter 3 (VGLUT3), and neurofilament 200 (NF200) in adult mice. Background: With the increasing use of mice as a model system to study headache mechanisms, it is important to understand the composition of dural afferent neurons in mice. In a previous study, we have measured the abundance of mouse dural afferent neurons that express neuropeptide calcitonin gene-related peptide as well as two TRP channels TRPV1 and TRPA1, respectively. Here, we conducted quantitative analysis of three other dural afferent subpopulations in adult mice. Methods: We used the fluorescent tracer Fluoro-Gold to retrogradely label dural afferent neurons in adult mice expressing enhanced green fluorescent protein in discrete subpopulations of trigeminal ganglion (TG) neurons. Mechanoreceptors with myelinated fibers were identified by NF200 immunoreactivity. We also conducted Ca2+-imaging experiments to test the overlap between TRPM8 and VGLUT3 expression in mouse primary afferent neurons (PANs). Results: The abundance of TRPM8-expressing neurons in dural afferent neurons was significantly lower than that in total TG neurons. The percentages of dural afferent neurons expressing VGLUT3 and NF200 were comparable to those of total TG neurons, respectively. TRPM8 agonist menthol evoked Ca2+ influx in less than 7% VGLUT3-expressing PANs in adult mice. Conclusions: TG neurons expressing TRPM8, VGLUT3, and NF200 all innervate adult mouse dura. TRPM8 and VGLUT3 are expressed in distinct subpopulations of PANs in adult mice. These results provide an anatomical basis to investigate headache mechanisms in mouse models. © 2017 American Headache Society.


Author Keywords
Dural afferent neurons;  Headache;  Migraine;  NF200;  TRPM8;  VGlut3


Document Type: Article in Press
Source: Scopus

 

13) 

Zhu, Z., Gorman, M.J., McKenzie, L.D., Chai, J.N., Hubert, C.G., Prager, B.C., Fernandez, E., Richner, J.M., Zhang, R., Shan, C., Tycksen, E., Wang, X., Shi, P.-Y., Diamond, M.S., Rich, J.N., Chheda, M.G.
Zika virus has oncolytic activity against glioblastoma stem cells
(2017) Journal of Experimental Medicine, 214 (10), pp. 2843-2857. Cited 1 time.

DOI: 10.1084/jem.20171093


a Department of Medicine, Division of Regenerative Medicine, University of California, School of Medicine, San Diego, La Jolla, CA, United States
b Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States
g The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, United States
h Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, United States
i Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, United States
j Genome Technology Access Center, Department of Genetics, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients. © 2017 Zhu et al.


Document Type: Article
Source: Scopus

 

14) 

Lean, R.E., Paul, R.A., Smyser, C.D., Rogers, C.E.
Maternal intelligence quotient (IQ) predicts IQ and language in very preterm children at age 5 years
(2017) Journal of Child Psychology and Psychiatry and Allied Disciplines, . Article in Press. 

DOI: 10.1111/jcpp.12810


a Department of Psychiatry Washington University School of Medicine St. Louis, MO USA
b Department of Neurology Washington University School of Medicine St. Louis, MO USA
c Department of Radiology Washington University School of Medicine St. Louis, MO USA
d Department of Pediatrics Washington University School of Medicine St. Louis, MO USA


Abstract
Background: Sociodemographic factors are linked to cognitive outcomes in children born very preterm (VPT; ≤30 weeks gestation). The influence of maternal intellectual ability, a heritable trait, is unknown. Also undetermined is the extent to which associations between maternal and child intellectual ability vary according to parenting behaviors that target cognitive stimulation in the home. Methods: At age 5 years, 84 VPT and 38 demographically matched full-term (FT) children underwent neurodevelopmental assessment. Children's intellectual ability was assessed using The Wechsler Preschool Primary Scale of Intelligence-III, and language was assessed with the Clinical Evaluation of Language Fundamentals Preschool-2. The Wechsler Test of Adult Reading estimated maternal intellectual ability. The StimQ-Preschool questionnaire provided a measure of cognitive stimulation in the home. Linear mixed-effects models examined independent effects and interactions between maternal intellectual ability and cognitive stimulation on children's outcomes. Results: After covariate adjustment, maternal intellectual ability was associated with child intellectual (p < .001) and language (p = .002) abilities. Stronger associations were observed in FT mother-child dyads (B = .63, p = .04) than VPT dyads (B = .42, p = .01). Mothers of VPT children reported lower levels of Parental Involvement in Developmental Advance (p = .007) and Parental Verbal Responsiveness (p = .04). Group differences in Parental Involvement in Developmental Advance, but not Parental Verbal Responsivity, persisted after adjusting for social background (p = .03). There was no evidence of an interaction between maternal intellectual ability and Parental Involvement in Developmental Advance (p = .34). Instead, maternal intellectual ability (p < .001) and Parental Involvement in Developmental Advance (p = .05) independently predicted VPT children's outcomes. Conclusions: Maternal intellectual ability is an important trait linked to VPT and FT children's intellectual and language outcomes. Prematurity increases variation in the heritability of intellectual ability and shifts children from the expected range based on maternal ability. Parental involvement in activities that help children master new skills may promote cognitive development in VPT children born to mothers of lower intellectual ability. © 2017 Association for Child and Adolescent Mental Health.


Author Keywords
Environmental influences;  Follow-up studies;  Intelligence;  Maternal factors;  Prematurity


Document Type: Article in Press
Source: Scopus

 

15) 

Lee, C., Jones, T.A.
Neuropharmacological targets for drug action in vestibular sensory pathways
(2017) Journal of Audiology and Otology, 21 (3), pp. 125-132. 

DOI: 10.7874/jao.2017.00171


a Department of Otolaryngology, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, 304 Barkley Memorial Center, Lincoln, NE, United States


Abstract
The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e., glutamate (Glu) and acetylcholine (ACh)] or alter their patterns of release. This review summarizes various efforts to identify drug targets including neurotransmitter and neuromodulator receptors in the vestibular sensory pathways. Identifying these receptor targets provides a strategic basis to use specific pharmacological tools to modify receptor function in the treatment and management of debilitating balance disorders. A review of the literature reveals that most investigations of the neuropharmacology of peripheral vestibular function have been performed using in vitro or ex vivo animal preparations rather than studying drug action on the normal intact vestibular system in situ. Such noninvasive approaches could aid the development of more accurate and effective intervention strategies for the treatment of dizziness and vertigo. The current review explores the major neuropharmacological targets for drug action in the vestibular system. © 2017 The Korean Audiological Society and Korean Otological Society.


Author Keywords
Dizziness;  Neuroactive substance;  Peripheral vestibular system;  Vertigo;  Vestibular suppressant


Document Type: Article
Source: Scopus

 

October 9, 2017  

1) 

Gross, J.H., Bertrand, M., Hirose, K.
Benign Rolandic epilepsy presenting like paradoxical vocal fold motion
(2017) International Journal of Pediatric Otorhinolaryngology, 102, pp. 154-156. 

DOI: 10.1016/j.ijporl.2017.09.021


a Washington University School of Medicine, Department of Otolaryngology, 660 South Euclid Avenue, Saint Louis, Missouri, United States
b Washington University School of Medicine, Department of Neurology, 660 South Euclid Avenue, Saint Louis, Missouri, United States


Abstract
Paradoxical vocal fold motion (PVFM) is characterized by vocal fold adduction during respiration. Benign Rolandic epilepsy (BRE) is the most common childhood epilepsy and can cause oropharyngolaryngeal or facial manifestations. A 9-year-old male presented with intermittent apnea lasting 30–60 seconds and presumed PVFM. The patient's physical and fiberoptic exam were normal. He was admitted and found to have episodes of oxygen desaturation, neck twitching, and tongue burning. An EEG revealed focal epilepsy. After starting anti-epileptic medications, he had resolution of symptoms. Our patient was eventually diagnosed with BRE, a focal onset epilepsy that can mimic primary otolaryngologic disease. © 2017 Elsevier B.V.


Author Keywords
Apnea;  Children;  Epilepsy;  Laryngeal spasm;  Paradoxical vocal fold motion


Document Type: Article
Source: Scopus

 

2) 

Lee, H.-C., Rudy, Y., Liang, H., Chen, C.-C., Luo, C.-H., Sheu, S.-H., Cui, J.
Pro-arrhythmogenic Effects of the V141M KCNQ1 Mutation in Short QT Syndrome and Its Potential Therapeutic Targets: Insights from Modeling
(2017) Journal of Medical and Biological Engineering, 37 (5), pp. 780-789. 

DOI: 10.1007/s40846-017-0257-x


a Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, St. Louis, MO, United States
b Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou 1st Rd, Kaohsiung, Taiwan
c Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
d Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
e Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
f Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan
g Department of Electric Engineering, National Cheng Kung University, Tainan, Taiwan


Abstract
Gain-of-function mutations in the pore-forming subunit of IKs channels, KCNQ1, lead to short QT syndrome (SQTS) and lethal arrhythmias. However, how mutant IKs channels cause SQTS and the possibility of IKs-specific pharmacological treatment remain unclear. V141M KCNQ1 is a SQTS associated mutation. We studied its effect on IKs gating properties and changes in the action potentials (AP) of human ventricular myocytes. Xenopus oocytes were used to study the gating mechanisms of expressed V141M KCNQ1/KCNE1 channels. Computational models were used to simulate human APs in endocardial, mid-myocardial, and epicardial ventricular myocytes with and without β-adrenergic stimulation. V141M KCNQ1 caused a gain-of-function in IKs characterized by increased current density, faster activation, and slower deactivation leading to IKs accumulation. V141M KCNQ1 also caused a leftward shift of the conductance-voltage curve compared to wild type (WT) IKs (V1/2 = 33.6 ± 4.0 mV for WT, and 24.0 ± 1.3 mV for heterozygous V141M). A Markov model of heterozygous V141M mutant IKs was developed and incorporated into the O’Hara–Rudy model. Compared to the WT, AP simulations demonstrated marked rate-dependent shortening of AP duration (APD) for V141M, predicting a SQTS phenotype. Transmural electrical heterogeneity was enhanced in heterozygous V141M AP simulations, especially under β-adrenergic stimulation. Computational simulations identified specific IK1 blockade as a beneficial pharmacologic target for reducing the transmural APD heterogeneity associated with V141M KCNQ1 mutation. V141M KCNQ1 mutation shortens ventricular APs and enhances transmural APD heterogeneity under β-adrenergic stimulation. Computational simulations identified IK1 blockers as a potential antiarrhythmic drug of choice for SQTS. © 2017, Taiwanese Society of Biomedical Engineering.


Author Keywords
Anti-arrhythmic;  Arrhythmia;  IKs;  KCNQ1;  Short QT syndrome


Document Type: Article
Source: Scopus

 

3) 

Lieu, J.E.C.
Variations in the prevalence of hearing loss in children: Truth or artifact?
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (9), pp. 935-936. 

DOI: 10.1001/jamaoto.2017.1172


Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, MO, United States


Document Type: Note
Source: Scopus

 

4) 

Piccirillo, J.F., Bauchner, H.
Expression of concern: Schietroma M, Cecilia EM, Carlei F, Sista F, De Santis G, Lancione L, Amicucci G. Dexamethasone for the prevention of recurrent laryngeal nerve palsy and other complications after thyroid surgery: A randomized double-blind placebo-controlled trial. JAMA Otolaryngol Head Neck Surg. 2013;139(5):471-478. doi:10.1001/jamaoto.2013.2821
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (9), p. 869. 

DOI: 10.1001/jamaoto.2017.1641


a JAMA Otolaryngology−Head and Neck Surgery, Chicago, IL, United States
b Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, MO, United States
c JAMA, Chicago, IL, United States


Document Type: Editorial
Source: Scopus

 

5) 

Waldron, M., Bucholz, K.K., Lian, M., Lessov-Schlaggar, C.N., Miller, R.H., Lynskey, M.T., Knopik, V.S., Madden, P.A.F., Heath, A.C.
Single motherhood, alcohol dependence, and smoking during pregnancy: A propensity score analysis
(2017) Journal of Studies on Alcohol and Drugs, 78 (5), pp. 745-753. 

DOI: 10.15288/jsad.2017.78.745


a Department of Counseling and Educational Psychology, School of Education, Indiana University, Bloomington, IN, United States
b Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
d Addictions Department, Institute of Psychiatry, Psychology & Neuroscience, King’s College, London, United Kingdom
e Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, United States
f Department of Psychiatry & Human Behavior, Warren Alpert School of Medicine, Brown University, Providence, RI, United States


Abstract
Objective: Few studies linking single motherhood and maternal smoking during pregnancy consider correlated risk from problem substance use beyond history of smoking and concurrent use of alcohol. In the present study, we used propensity score methods to examine whether the risk of smoking during pregnancy associated with single motherhood is the result of potential confounders, including alcohol dependence. Method: Data were drawn from mothers participating in a birth cohort study of their female like-sex twin offspring (n = 257 African ancestry; n = 1,711 European or other ancestry). We conducted standard logistic regression models predicting smoking during pregnancy from single motherhood at twins’ birth, followed by propensity score analyses comparing single-mother and two-parent families stratified by predicted probability of single motherhood. Results: In standard models, single motherhood predicted increased risk of smoking during pregnancy in European ancestry but not African ancestry families. In propensity score analyses, rates of smoking during pregnancy were elevated in single-mother relative to two-parent European ancestry families across much of the spectrum a priori risk of single motherhood. Among African ancestry families, within-strata comparisons of smoking during pregnancy by single-mother status were nonsignificant. Conclusions: These findings highlight single motherhood as a unique risk factor for smoking during pregnancy in European ancestry mothers, over and above alcohol dependence. Additional research is needed to identify risks, beyond single motherhood, associated with smoking during pregnancy in African ancestry mothers. © 2017, Alcohol Research Documentation Inc. All rights reserved.


Document Type: Article
Source: Scopus

 

6) 

Bidwell, L.C., Marceau, K., Brick, L.A., Karoly, H.C., Todorov, A.A., Palmer, R.H., Heath, A.C., Knopik, V.S.
Prenatal exposure effects on early adolescent substance use: Preliminary evidence from a genetically informed bayesian approach
(2017) Journal of Studies on Alcohol and Drugs, 78 (5), pp. 789-794. 

DOI: 10.15288/jsad.2017.78.789


a Institute of Cognitive Science, University of Colorado Boulder, Boulder, CO, United States
b Division of Behavioral Genetics, Brown University, Providence, RI, United States
c Department of Psychiatry, Rhode Island Hospital, Providence, RI, United States
d Center for Alcohol and Addiction Studies, Brown University, Providence, RI, United States
e Department of Psychiatry and Human Behavior, Brown University, Providence, RI, United States
f Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
g Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Objective: Given the controversy surrounding the question of whether there are direct or causal effects of exposure to maternal smoking during pregnancy (SDP) on offspring outcomes such as substance use during the adolescent years, we sought to test, on a preliminary basis, within- and between-family associations of SDP and initiation of substance use early in adolescence (by age 15 years) using a discordant sibling design. Method: We used a sibling-comparison approach in a sample of 173 families drawn from the state of Missouri, wherein mothers were discordant for smoking behaviors between two different pregnancies, to test for associations of SDP and initiation of substance use in a younger adolescent cohort. The discordant siblingcomparison approach allows for disentangling familial effects from direct effects of SDP through the purposeful collection of data from siblings within the same family with differential exposure. Results: There were no between- or within-family effects of SDP on initiation of any type of substance use (alcohol, marijuana, smoking, and other drug classes), suggesting that SDP does not exert a direct effect on substance use in early adolescence. Conclusions: Preliminary findings did not support an association of SDP and initiation of substance use in this younger adolescent sample. Studies such as this one can help build a body of evidence to explain whether associations of SDP and adolescent outcomes reflect a direct effect of SPD or may instead be attributable to familial confounders that are controlled in the discordant sibling design. © 2017, Alcohol Research Documentation Inc. All rights reserved.


Document Type: Article
Source: Scopus

 

7) 

Maitree, R., Perez-Carrillo, G.J.G., Shimony, J.S., Gach, H.M., Chundury, A., Roach, M., Li, H.H., Yang, D.
Adaptive anatomical preservation optimal denoising for radiation therapy daily MRI
(2017) Journal of Medical Imaging, 4 (3), art. no. 034004, . 

DOI: 10.1117/1.JMI.4.3.034004


a Washington University School of Medicine, Department of Radiation Oncology, St. Louis, MO, United States
b Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO, United States
c University of Arizona, Department of Radiology, Tucson, AZ, United States
d Washington University School of Medicine, Department of Biomedical Engineering, St. Louis, MO, United States


Abstract
Low-field magnetic resonance imaging (MRI) has recently been integrated with radiation therapy systems to provide image guidance for daily cancer radiation treatments. The main benefit of the low-field strength is minimal electron return effects. The main disadvantage of low-field strength is increased image noise compared to diagnostic MRIs conducted at 1.5 T or higher. The increased image noise affects both the discernibility of soft tissues and the accuracy of further image processing tasks for both clinical and research applications, such as tumor tracking, feature analysis, image segmentation, and image registration. An innovative method, adaptive anatomical preservation optimal denoising (AAPOD), was developed for optimal image denoising, i.e., to maximally reduce noise while preserving the tissue boundaries. AAPOD employs a series of adaptive nonlocal mean (ANLM) denoising trials with increasing denoising filter strength (i.e., the block similarity filtering parameter in the ANLM algorithm), and then detects the tissue boundary losses on the differences of sequentially denoised images using a zero-crossing edge detection method. The optimal denoising filter strength per voxel is determined by identifying the denoising filter strength value at which boundary losses start to appear around the voxel. The final denoising result is generated by applying the ANLM denoising method with the optimal per-voxel denoising filter strengths. The experimental results demonstrated that AAPOD was capable of reducing noise adaptively and optimally while avoiding tissue boundary losses. AAPOD is useful for improving the quality of MRIs with low-contrast-to-noise ratios and could be applied to other medical imaging modalities, e.g., computed tomography. © 2017 Society of Photo-Optical Instrumentation Engineers (SPIE).


Author Keywords
image guidance;  image processing;  image restoration;  magnetic resonance imaging;  medical imaging;  noise reduction;  radiation therapy


Document Type: Article
Source: Scopus

 

8) 

Lean, R.E., Paul, R.A., Smyser, C.D., Rogers, C.E.
Maternal intelligence quotient (IQ) predicts IQ and language in very preterm children at age 5 years
(2017) Journal of Child Psychology and Psychiatry and Allied Disciplines, . Article in Press. 

DOI: 10.1111/jcpp.12810


a Department of Psychiatry Washington University School of Medicine St. Louis, MO USA
b Department of Neurology Washington University School of Medicine St. Louis, MO USA
c Department of Radiology Washington University School of Medicine St. Louis, MO USA
d Department of Pediatrics Washington University School of Medicine St. Louis, MO USA


Abstract
Background: Sociodemographic factors are linked to cognitive outcomes in children born very preterm (VPT; ≤30 weeks gestation). The influence of maternal intellectual ability, a heritable trait, is unknown. Also undetermined is the extent to which associations between maternal and child intellectual ability vary according to parenting behaviors that target cognitive stimulation in the home. Methods: At age 5 years, 84 VPT and 38 demographically matched full-term (FT) children underwent neurodevelopmental assessment. Children's intellectual ability was assessed using The Wechsler Preschool Primary Scale of Intelligence-III, and language was assessed with the Clinical Evaluation of Language Fundamentals Preschool-2. The Wechsler Test of Adult Reading estimated maternal intellectual ability. The StimQ-Preschool questionnaire provided a measure of cognitive stimulation in the home. Linear mixed-effects models examined independent effects and interactions between maternal intellectual ability and cognitive stimulation on children's outcomes. Results: After covariate adjustment, maternal intellectual ability was associated with child intellectual (p < .001) and language (p = .002) abilities. Stronger associations were observed in FT mother-child dyads (B = .63, p = .04) than VPT dyads (B = .42, p = .01). Mothers of VPT children reported lower levels of Parental Involvement in Developmental Advance (p = .007) and Parental Verbal Responsiveness (p = .04). Group differences in Parental Involvement in Developmental Advance, but not Parental Verbal Responsivity, persisted after adjusting for social background (p = .03). There was no evidence of an interaction between maternal intellectual ability and Parental Involvement in Developmental Advance (p = .34). Instead, maternal intellectual ability (p < .001) and Parental Involvement in Developmental Advance (p = .05) independently predicted VPT children's outcomes. Conclusions: Maternal intellectual ability is an important trait linked to VPT and FT children's intellectual and language outcomes. Prematurity increases variation in the heritability of intellectual ability and shifts children from the expected range based on maternal ability. Parental involvement in activities that help children master new skills may promote cognitive development in VPT children born to mothers of lower intellectual ability. © 2017 Association for Child and Adolescent Mental Health.


Author Keywords
Environmental influences;  Follow-up studies;  Intelligence;  Maternal factors;  Prematurity


Document Type: Article in Press
Source: Scopus

 

9) 

Cruchaga, C., Del-Aguila, J.L., Saef, B., Black, K., Fernandez, M.V., Budde, J., Ibanez, L., Kapoor, M., Tosto, G., Mayeux, R.P., Holtzman, D.M., Fagan, A.M., Morris, J.C., Bateman, R.J., Goate, A.M., Harari, O.
Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms
(2017) Alzheimer's and Dementia, . Article in Press. 

DOI: 10.1016/j.jalz.2017.08.013


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
b Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
d Ronald M. Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA
e Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY, USA
f Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY, USA
g Department of Neurology, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY, USA
h School of Medicine, Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic
i Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA


Abstract
Objective: To determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD). Methods: Polygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk. Results: We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. The highest association of the PRS and risk (odds ratio [OR] = 2.27; P = 1.29 × 10-7) was observed in sEOAD, followed by fLOAD (OR = 1.75; P = 1.12 × 10-7) and sLOAD (OR = 1.40; P = 1.21 × 10-3). The PRS was associated with cerebrospinal fluid ptau181-Aβ42 on eADAD (P = 4.36 × 10-2). Conclusion: Our analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset. © 2017 the Alzheimer's Association.


Author Keywords
Age at onset;  APOE;  APP;  Area under the curve;  Aβ;  Cerebrospinal fluid;  Disease modifier;  Dominantly inherited Alzheimer network;  Early-onset Alzheimer's disease;  Early-onset autosomal dominant;  Genetic architecture;  Genetic risk factor;  Late-onset Alzheimer's disease;  Polygenic risk score;  PSEN1;  PSEN2;  Sporadic late-onset Alzheimer's disease;  Tau


Document Type: Article in Press
Source: Scopus

 

10) 

Ren, L., Chang, M.J., Zhang, Z., Dhaka, A., Guo, Z., Cao, Y.-Q.
Quantitative Analysis of Mouse Dural Afferent Neurons Expressing TRPM8, VGLUT3, and NF200
(2017) Headache, . Article in Press. 

DOI: 10.1111/head.13188


a Washington University Pain Center and Department of Anesthesiology, Washington University School of MedicineSt. Louis, MO USA
b Department of Biological Structure, Neurobiology and Behavior Graduate ProgramUniversity of WashingtonSeattle, WA USA


Abstract
Objective: To quantify the abundance of dural afferent neurons expressing transient receptor potential channel melastatin 8 (TRPM8), vesicular glutamate transporter 3 (VGLUT3), and neurofilament 200 (NF200) in adult mice. Background: With the increasing use of mice as a model system to study headache mechanisms, it is important to understand the composition of dural afferent neurons in mice. In a previous study, we have measured the abundance of mouse dural afferent neurons that express neuropeptide calcitonin gene-related peptide as well as two TRP channels TRPV1 and TRPA1, respectively. Here, we conducted quantitative analysis of three other dural afferent subpopulations in adult mice. Methods: We used the fluorescent tracer Fluoro-Gold to retrogradely label dural afferent neurons in adult mice expressing enhanced green fluorescent protein in discrete subpopulations of trigeminal ganglion (TG) neurons. Mechanoreceptors with myelinated fibers were identified by NF200 immunoreactivity. We also conducted Ca2+-imaging experiments to test the overlap between TRPM8 and VGLUT3 expression in mouse primary afferent neurons (PANs). Results: The abundance of TRPM8-expressing neurons in dural afferent neurons was significantly lower than that in total TG neurons. The percentages of dural afferent neurons expressing VGLUT3 and NF200 were comparable to those of total TG neurons, respectively. TRPM8 agonist menthol evoked Ca2+ influx in less than 7% VGLUT3-expressing PANs in adult mice. Conclusions: TG neurons expressing TRPM8, VGLUT3, and NF200 all innervate adult mouse dura. TRPM8 and VGLUT3 are expressed in distinct subpopulations of PANs in adult mice. These results provide an anatomical basis to investigate headache mechanisms in mouse models. © 2017 American Headache Society.


Author Keywords
Dural afferent neurons;  Headache;  Migraine;  NF200;  TRPM8;  VGlut3


Document Type: Article in Press
Source: Scopus

 

October 2, 2017 

1) 

Dixon-Gordon, K.L., Conkey, L.C., Whalen, D.J.
Recent advances in understanding physical health problems in personality disorders
(2018) Current Opinion in Psychology, 21, pp. 1-5. 

DOI: 10.1016/j.copsyc.2017.08.036


a University of Massachusetts Amherst, Department of Psychological and Brain Sciences, 135 Hicks Way, Amherst, MA, United States
b Washington University School of Medicine, Department of Psychiatry, Box 8511, St. Louis, MO, United States


Abstract
Personality disorders are associated with a range of adverse health outcomes, contributing to the high healthcare utilization seen in patients with these disorders. A growing literature supports a robust association of personality disorders and health problems. The primary aim of this article is to summarize the most recent research documenting the associations between personality disorders and health conditions. Extending past reviews, we discuss the association of personality disorders with chronic physical illnesses, sleep disturbances, pain conditions, and obesity. We provide recommendations for future research in this area. © 2017 Elsevier Ltd


Document Type: Review
Source: Scopus

 

2) 

Nguyen, T.-V., Wu, M., Lew, J., Albaugh, M.D., Botteron, K.N., Hudziak, J.J., Fonov, V.S., Collins, D.L., Campbell, B.C., Booij, L., Herba, C., Monnier, P., Ducharme, S., McCracken, J.T.
Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development
(2017) Psychoneuroendocrinology, 86, pp. 110-121. 

DOI: 10.1016/j.psyneuen.2017.09.013


a Department of Psychiatry, McGill University, Montreal, QC, Canada
b Department of Obstetrics-Gynecology, McGill University Health Center, Montreal, QC, Canada
c Research Institute of the McGill University Health Center, Montreal, QC, Canada
d Department of Psychology, McGill University, Montreal, QC, Canada
e Department of Psychology, University of Vermont, College of Medicine, Burlington, VT, United States
f Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
g Brain Development Cooperative Group, United States
h McConnell Brain imaging Centre, Montreal Neurological Institute, Montreal, QC, Canada
i Department of Anthropology, University of Wisconsin-Milwaukee, Milwaukee, WI, United States
j Department of Psychology, Concordia University, Montreal, QC, Canada
k CHU Sainte Justine Hospital Research Centre, University of Montreal, Montreal, QC, Canada
l Department of Psychology, Université du Québec à Montréal, Montreal, QC, Canada
m Department of Neurology & Neurosurgery, McGill University, Montreal, QC, Canada
n Department of Child and Adolescent Psychiatry, University of California in Los Angeles, Los Angeles, CA, United States


Abstract
Existing studies suggest that dehydroepiandrosterone (DHEA) may be important for human brain development and cognition. For example, molecular studies have hinted at the critical role of DHEA in enhancing brain plasticity. Studies of human brain development also support the notion that DHEA is involved in preserving cortical plasticity. Further, some, though not all, studies show that DHEA administration may lead to improvements in working memory in adults. Yet these findings remain limited by an incomplete understanding of the specific neuroanatomical mechanisms through which DHEA may impact the CNS during development. Here we examined associations between DHEA, cortico-hippocampal structural covariance, and working memory (216 participants [female=123], age range 6–22 years old, mean age: 13.6 +/−3.6 years, each followed for a maximum of 3 visits over the course of 4 years). In addition to administering performance-based, spatial working memory tests to these children, we also collected ecological, parent ratings of working memory in everyday situations. We found that increasingly higher DHEA levels were associated with a shift toward positive insular-hippocampal and occipito-hippocampal structural covariance. In turn, DHEA-related insular-hippocampal covariance was associated with lower spatial working memory but higher overall working memory as measured by the ecological parent ratings. Taken together with previous research, these results support the hypothesis that DHEA may optimize cortical functions related to general attentional and working memory processes, but impair the development of bottom-up, hippocampal-to-cortical connections, resulting in impaired encoding of spatial cues. © 2017 Elsevier Ltd


Author Keywords
Adolescence;  Androgen;  Attention;  Brain development;  Cortical thickness;  DHEA;  Puberty;  Structural magnetic resonance imaging


Document Type: Article
Source: Scopus

 

3) 

Guo, P., Yu, Y., Li, H., Zhang, D., Gong, A., Li, S., Liu, W., Cheng, L., Qiu, Y., Yao, W., Li, L., Feng, Y.
TGF-â1-induced miR-503 controls cell growth and apoptosis by targeting PDCD4 in glioblastoma cells
(2017) Scientific Reports, 7 (1), art. no. 11569, . 

DOI: 10.1038/s41598-017-11885-8


a Department of Neurosurgery, Qingdao University, Qingdao, China
b Department of Gastroenterology, Qingdao University, Qingdao, China
c Division of Oncology, Department of Internal Medicine, Washington University, School of Medicine, Saint Louis, MO, United States
d Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
e Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China


Abstract
Aberrant expression of microRNAs hae been shown to be closely associated with glioblastoma cell proliferation, apoptosis and drug resistance. However, mechanisms underlying the role of mcroRNAs in glioblastoma cell growth and apoptosis are not fully understood. In this study, we report that miR-503 is overexpressed in glioblastoma tissue compared with normal human brain tissue. Mechanistically, miR-503 can be induced by TGF-â1 at the transcriptional level by binding the smad2/3 binding elements in the promoter. Ectopic overexpression of miR-503 promotes cell growth and inhibits apoptosis by targeting PDCD4. In contrast, inhibition of miR-503 reduces cell growth. Furthermore, miR-503 inhibitor augments the growth inhibitory effect of temozolomide in glioblastoma cells. These results establish miR-503 as a promising molecular target for glioblastoma therapy. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

4) 

Sinacore, D.R., Hastings, M.K., Bohnert, K.L., Strube, M.J., Gutekunst, D.J., Johnson, J.E.
Immobilization-induced osteolysis and recovery in neuropathic foot impairments
(2017) Bone, 105, pp. 237-244. 

DOI: 10.1016/j.bone.2017.09.009


a Applied Kinesiology Laboratory, Washington University School of Medicine, Program in Physical Therapy, Campus Box 8502, Saint Louis, MO, United States
b Dept of Psychology, Washington University, Campus Box 1125, Saint Louis, MO, United States
c Musculoskeletal Biomechanics Laboratory, Program in Physical Therapy, Doisy College of Health Sciences, Saint Louis University, St. Louis, MO, United States
d Dept Orthopaedic Surgery, Washington University School of Medicine, Campus Box 8233, Foot & Ankle Service, Saint Louis, MO, United States


Abstract
Background Neuropathic foot impairments treated with immobilization and off-loading result in osteolysis. In order to prescribe and optimize rehabilitation programs after immobilization we need to understand the magnitude of pedal osteolysis after immobilization and the time course for recovery. Objective To determine differences in a) foot skin temperature; b) calcaneal bone mineral density (BMD) after immobilization; c) calcaneal BMD after 33–53 weeks of recovery; and d) percent of feet classified as osteopenic or osteoporotic after recovery in participants with neuropathic plantar ulcers (NPU) compared to Charcot neuroarthropathy (CNA). Methods Fifty-five participants with peripheral neuropathy were studied. Twenty-eight participants had NPU and 27 participants had CNA. Bilateral foot skin temperature was assessed before immobilization and bilateral calcaneal BMD was assessed before immobilization, after immobilization and after recovery using quantitative ultrasonometry. Results Before immobilization, skin temperature differences in CNA between their index and contralateral foot were markedly higher than NPU feet (3.0 degree C versus 0.7 degree C, respectively, p &lt; 0.01); BMD in NPU immobilized feet averaged 486 ± 136 mg/cm2, and CNA immobilized feet averaged 456 ± 138 mg/cm2, p &gt; 0.05). After immobilization, index NPU feet lost 27 mg/cm2; CNA feet lost 47 mg/cm2 of BMD, p &lt; 0.05. After recovery, 61% of NPU index feet and 84% of CNA index feet were classified as osteopenic or osteoporotic. Conclusions There was a greater osteolysis after immobilization with an attenuated recovery in CNA feet compared to NPU feet. The attenuated recovery of pedal BMD in CNA feet resulted in a greater percentage of feet classified as osteoporotic and osteopenic. © 2017


Author Keywords
Bone loss;  Neuropathic (Charcot) osteoarthropathy;  Neuropathic plantar ulcers;  Quantitative ultrasonometry;  Total contact casting


Document Type: Article
Source: Scopus

 

5) 

Lerman-Sinkoff, D.B., Sui, J., Rachakonda, S., Kandala, S., Calhoun, V.D., Barch, D.M.
Multimodal neural correlates of cognitive control in the Human Connectome Project
(2017) NeuroImage, 163, pp. 41-54. 

DOI: 10.1016/j.neuroimage.2017.08.081


a Department of Biomedical Engineering, Washington University in St. Louis, United States
b Medical Scientist Training Program, Washington University in St. Louis, United States
c CAS, Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Beijing, China
d Brainnetome Center & National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China
e Medical Image Analysis Lab, The Mind Research Network, United States
f Department of Psychiatry, Washington University in St. Louis, United States
g Department of Electrical and Computer Engineering, University of New Mexico, United States
h Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
i Department of Radiology, Washington University in St. Louis, United States


Abstract
Cognitive control is a construct that refers to the set of functions that enable decision-making and task performance through the representation of task states, goals, and rules. The neural correlates of cognitive control have been studied in humans using a wide variety of neuroimaging modalities, including structural MRI, resting-state fMRI, and task-based fMRI. The results from each of these modalities independently have implicated the involvement of a number of brain regions in cognitive control, including dorsal prefrontal cortex, and frontal parietal and cingulo-opercular brain networks. However, it is not clear how the results from a single modality relate to results in other modalities. Recent developments in multimodal image analysis methods provide an avenue for answering such questions and could yield more integrated models of the neural correlates of cognitive control. In this study, we used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) to identify multimodal patterns of variation related to cognitive control. We used two independent cohorts of participants from the Human Connectome Project, each of which had data from four imaging modalities. We replicated the findings from the first cohort in the second cohort using both independent and predictive analyses. The independent analyses identified a component in each cohort that was highly similar to the other and significantly correlated with cognitive control performance. The replication by prediction analyses identified two independent components that were significantly correlated with cognitive control performance in the first cohort and significantly predictive of performance in the second cohort. These components identified positive relationships across the modalities in neural regions related to both dynamic and stable aspects of task control, including regions in both the frontal-parietal and cingulo-opercular networks, as well as regions hypothesized to be modulated by cognitive control signaling, such as visual cortex. Taken together, these results illustrate the potential utility of multi-modal analyses in identifying the neural correlates of cognitive control across different indicators of brain structure and function. © 2017 Elsevier Inc.


Author Keywords
Cognitive control;  mCCA + jICA;  Multimodal fusion


Document Type: Article
Source: Scopus

 

6) 

Shahim, P., Holleran, L., Kim, J.H., Brody, D.L.
Test-retest reliability of high spatial resolution diffusion tensor and diffusion kurtosis imaging
(2017) Scientific Reports, 7 (1), art. no. 11141, . 

DOI: 10.1038/s41598-017-11747-3


a Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
b Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden
c Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
d Hope Center for Neurological Disorders, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
We assessed the test-retest reliability of high spatial resolution diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Diffusion MRI was acquired using a Siemens 3 Tesla Prisma scanner with 80 mT/m gradients and a 32-channel head coil from each of 3 concussive traumatic brain injury (cTBI) patients and 4 controls twice 0 to 24 days apart. Coefficients of variation (CoV) for DTI parameters were calculated in each DTI Studio parcellated white matter tract at 1.25 mm and 1.75 mm isotropic voxel resolution, as well as DKI parameters at 1.75 mm isotropic. Overall, fractional anisotropy had the best reliability, with mean CoV at 5% for 1.25 mm and 3.5% for 1.75 mm isotropic voxels. Mean CoV for the other DTI metrics were <7.0% for both 1.25 and 1.75 mm isotropic voxels. The mean CoV was ≤4.5% across the DKI metrics. In the commonly injured orbitofrontal and temporal pole regions CoV was <3.5% for all parameters. Thus, with appropriate processing, high spatial resolution advanced diffusion MRI has good to excellent test-retest reproducibility in both human cTBI patients and controls. However, further technical improvements will be needed to reliably discern the most subtle diffusion abnormalities, especially at high spatial resolution. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

7) 

Sha, S.J., Miller, Z.A., Min, S.-W., Zhou, Y., Brown, J., Mitic, L.L., Karydas, A., Koestler, M., Tsai, R., Corbetta-Rastelli, C., Lin, S., Hare, E., Fields, S., Fleischmann, K.E., Powers, R., Fitch, R., Martens, L.H., Shamloo, M., Fagan, A.M., Farese, R.V., Jr., Pearlman, R., Seeley, W., Miller, B.L., Gan, L., Boxer, A.L.
An 8-week, open-label, dose-finding study of nimodipine for the treatment of progranulin insufficiency from GRN gene mutations
(2017) Alzheimer's and Dementia: Translational Research and Clinical Interventions, 3 (4), pp. 507-512. 

DOI: 10.1016/j.trci.2017.08.002


a Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
b Gladstone Institute of Neurodegenerative Disease, San Francisco, CA, United States
c Bluefield Project to Cure Frontotemporal Dementia, San Francisco, CA, United States
d Investigational Drug Service, UCSF Medical Center, San Francisco, CA, United States
e Division of Cardiology, University of California, School of Medicine, San Francisco, CA, United States
f Gladstone Institute of Cardiovascular Disease, San Francisco, CA, United States
g Institute for Neuro-Innovation and Translational Neurosciences, Stanford, CA, United States
h Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
i Stanford Center for Memory Disorders, Stanford University, Stanford, CA, United States
j Genentech, Inc, South San Francisco, CA, United States
k University of California, School of Medicine, San Francisco, CA, United States
l Johns Hopkins School of Medicine, Baltimore, MD, United States
m Michigan State University, College of Osteopathic Medicine, East Lansing, MI, United States
n Dementia Discovery Fund, Boston, MA, United States
o Harvard School of Public Health, Boston, MA, United States


Abstract
Introduction Frontotemporal lobar degeneration–causing mutations in the progranulin (GRN) gene reduce progranulin protein (PGRN) levels, suggesting that restoring PGRN in mutation carriers may be therapeutic. Nimodipine, a Food and Drug Administration–approved blood-brain barrier-penetrant calcium channel blocker, increased PGRN levels in PGRN-deficient murine models. We sought to assess safety and tolerability of oral nimodipine in human GRN mutation carriers. Methods We performed an open-label, 8-week, dose-finding, phase 1 clinical trial in eight GRN mutation carriers to assess the safety and tolerability of nimodipine and assayed fluid and radiologic markers to investigate therapeutic endpoints. Results There were no serious adverse events; however, PGRN concentrations (cerebrospinal fluid and plasma) did not change significantly following treatment (percent changes of −5.2 ± 10.9% in plasma and −10.2 ± 7.8% in cerebrospinal fluid). Measurable atrophy within the left middle frontal gyrus was observed over an 8-week period. Discussion While well tolerated, nimodipine treatment did not alter PGRN concentrations or secondary outcomes. © 2017 The Authors


Author Keywords
Dementia;  Frontotemporal dementia;  Genetics;  Nimodipine;  Progranulin


Document Type: Article
Source: Scopus

 

8) 

Roth, J., Ber, R., Wisoff, J.H., Hidalgo, E.T., Limbrick, D.D., Berger, D.S., Thomale, U.W., Schulz, M., Cinalli, G., Santoro, C., Constantini, S.
Endoscopic Third Ventriculostomy in Patients with Neurofibromatosis Type 1: A Multicenter International Experience
(2017) World Neurosurgery, 107, pp. 623-629. 

DOI: 10.1016/j.wneu.2017.08.053


a Department of Pediatric Neurosurgery, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel
b Division of Pediatric Neurosurgery, NYU Langone Medical Center, New York, New York, United States
c Pediatric Neurosurgery, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, United States
d Pediatric Neurosurgery, Charité Universitaetsmedizin, Berlin, Germany
e Division of Pediatric Neurosurgery, Santobono-Pausilipon Children's Hospital, Naples, Italy
f Department of Woman, Child, General and Specialistic Surgery - “Luigi Vanvitelli“ Campania University, Naples, Italy


Abstract
Background Hydrocephalus in patients with neurofibromatosis (NF) type 1 is usually obstructive and may arise secondary to tumoral or nontumoral causes. Treatment of hydrocephalus in these patients is often challenging owing to combined pathologies and unique anatomic changes. The use of endoscopic third ventriculostomy (ETV) as treatment has rarely been described in this group. We aimed to characterize indications, considerations, and outcome of ETV in patients with NF 1 gathered in a multicenter international cohort. Methods Five centers participated in this retrospective study. Following institutional review board approval, data and images were collected. Patients of all ages with NF 1 who underwent ETV for treatment of obstructive hydrocephalus were included. Patients who had no postoperative radiologic or clinical follow-up were excluded. ETV failure was defined as recurrent clinical or radiologic signs of hydrocephalus. Results The study included 42 patients. Common etiologies for hydrocephalus were aqueductal/tectal tumor (31%), aqueductal web (26%), and aqueductal stenosis owing to NF-related changes (14%). Ten patients had a preoperative diagnosis of optic pathway glioma. ETV failures were identified in 6 patients within 1 month, in 3 patients within 9 months, and in 1 patient within 4 years. ETV was successful in 32 patients (76%) with a mean follow up of 59.4 months ± 50.9 (range, 4 months to 15 years). Conclusions ETV is a safe treatment for selected patients with NF 1 and obstructive hydrocephalus. Individual anatomic and pathologic aspects should be taken into consideration. © 2017 Elsevier Inc.


Author Keywords
Endoscopic third ventriculostomy;  Hydrocephalus;  Neurofibromatosis type 1;  Ommaya;  Optic pathway glioma;  Stent


Document Type: Article
Source: Scopus

 

9) 

Park, L.R., Teagle, H.F.B., Brown, K.D., Gagnon, E.B., Woodard, J.S., Buchman, C.A.
Audiological Outcomes and Map Characteristics in Children with Perimodiolar and Slim Straight Array Cochlear Implants in Opposite Ears
(2017) Otology and Neurotology, 38 (9), pp. e320-e326. 

DOI: 10.1097/MAO.0000000000001539


a Children's Cochlear Implant Center at University of North Carolina, Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
b Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Objective: To identify differences in outcomes and map characteristics in pediatric bilateral cochlear implants with modiolar conforming and lateral wall arrays in opposite ears. Study Design: Retrospective case series. Setting: Tertiary care pediatric referral center. Patients: Fourteen children who received a perimodiolar array in one ear and a slim straight array in the opposite ear in sequential surgeries. Interventions: None. Main Outcome Measures: Consonant-nucleus-consonant test (CNC) word recognition score, battery life, power levels, electrical compound action potential (ECAP) thresholds, and electrical threshold and comfort charge levels. Results: Speech perception outcomes were poorer in the lateral wall ears than the perimodiolar ears, and scores in the bilateral condition were better than with the lateral wall device alone. Sequential placement was a factor with differences in preoperative candidacy time correlating with greater difference in speech perception. There was no difference in charge levels between ears, in spite of higher ECAP threshold values for the lateral wall devices. Conclusion: While bilateral speech perception was good, speech perception with the lateral wall device alone was poorer. This cannot be explained solely by the device, as differences in preoperative candidacy time were a significant factor. ECAP thresholds are significantly higher for lateral wall electrodes, but that did not translate in to higher psychophysical measurements. Copyright © 2017 Otology & Neurotology, Inc.


Author Keywords
Bilateral;  Charge level;  Cochlear implant;  Contour advance;  Ecap;  Lateral wall;  Pediatric;  Perimodiolar;  Slim straight;  Speech perception


Document Type: Article
Source: Scopus

 

10) 

Chen, S.Y., Mancuso, D.M., Lalwani, A.K.
Response to "letter to Editor" Skin Necrosis after Implantation with the Baha Attract: A Case Report and Review of the Literature
(2017) Otology and Neurotology, 38 (9), p. 1383. 

DOI: 10.1097/MAO.0000000000001557


a Department of Otolaryngology-Head and Neck Surgery, Washington University in St. Louis, St. Louis, MO, United States
b Division of Otology, Neurotology and Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Columbia University College of Physicians and Surges, New York, NY, United States
c NewYork Presbyterian Hospital, Columbia University Medical Center, New York, NY, United States


Document Type: Letter
Source: Scopus

 

11) 

Kafashan, M., Ching, S.
Recurrent networks with soft-thresholding nonlinearities for lightweight coding
(2017) Neural Networks, 94, pp. 212-219. 

DOI: 10.1016/j.neunet.2017.07.008


a Department of Electrical and Systems Engineering, Washington University in St. Louis, One Brookings Drive, Campus Box 1042MO, United States
b Division of Biology and Biomedical Sciences, Washington University in St. Louis, One Brookings Drive, Campus Box 1042MO, United States
c Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, BostonMA, United States


Abstract
A long-standing and influential hypothesis in neural information processing is that early sensory networks adapt themselves to produce efficient codes of afferent inputs. Here, we show how a nonlinear recurrent network provides an optimal solution for the efficient coding of an afferent input and its history. We specifically consider the problem of producing lightweight codes, ones that minimize both l1 and l2 constraints on sparsity and energy, respectively. When embedded in a linear coding paradigm, this problem results in a non-smooth convex optimization problem. We employ a proximal gradient descent technique to develop the solution, showing that the optimal code is realized through a recurrent network endowed with a nonlinear soft thresholding operator. The training of the network connection weights is readily achieved through gradient-based local learning. If such learning is assumed to occur on a slower time-scale than the (faster) recurrent dynamics, then the network as a whole converges to an optimal set of codes and weights via what is, in effect, an alternative minimization procedure. Our results show how the addition of thresholding nonlinearities to a recurrent network may enable the production of lightweight, history-sensitive encoding schemes. © 2017 Elsevier Ltd


Author Keywords
Efficient sparse coding;  Neural networks;  Proximal gradient descent;  Short-term memory;  Unsupervised learning


Document Type: Article
Source: Scopus

 

12) 

Kaufman, D.M., Wu, X., Scott, B.A., Itani, O.A., Van Gilst, M.R., Bruce, J.E., Crowder, C.M.
Ageing and hypoxia cause protein aggregation in mitochondria
(2017) Cell Death and Differentiation, 24 (10), pp. 1730-1738. 

DOI: 10.1038/cdd.2017.101


a Department of Anesthesiology and Pain Medicine, University of Washington, Department of Genome Sciences, 1959 NE Pacific Street, Seattle, WA, United States
b Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, United States
c Department of Genome Sciences, University of Washington, Seattle, WA, United States
d Department of Chemistry, University of Washington, Seattle, WA, United States


Abstract
Aggregation of cytosolic proteins is a pathological finding in disease states, including ageing and neurodegenerative diseases. We have previously reported that hypoxia induces protein misfolding in Caenorhabditis elegans mitochondria, and electron micrographs suggested protein aggregates. Here, we seek to determine whether mitochondrial proteins actually aggregate after hypoxia and other cellular stresses. To enrich for mitochondrial proteins that might aggregate, we performed a proteomics analysis on purified C. elegans mitochondria to identify relatively insoluble proteins under normal conditions (110 proteins identified) or after sublethal hypoxia (65 proteins). A GFP-tagged mitochondrial protein (UCR-11 - a complex III electron transport chain protein) in the normally insoluble set was found to form widespread aggregates in mitochondria after hypoxia. Five other GFP-tagged mitochondrial proteins in the normally insoluble set similarly form hypoxia-induced aggregates. Two GFP-tagged mitochondrial proteins from the soluble set as well as a mitochondrial-targeted GFP did not form aggregates. Ageing also resulted in aggregates. The number of hypoxia-induced aggregates was regulated by the mitochondrial unfolded protein response (UPRmt) master transcriptional regulator ATFS-1, which has been shown to be hypoxia protective. An atfs-1(loss-of-function) mutant and RNAi construct reduced the number of aggregates while an atfs-1(gain-of-function) mutant increased aggregates. Our work demonstrates that mitochondrial protein aggregation occurs with hypoxic injury and ageing in C. elegans. The UPRmt regulates aggregation and may protect from hypoxia by promoting aggregation of misfolded proteins. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1350-9047/17.


Document Type: Article
Source: Scopus

 

13) 

Griffiths, H., Goyal, M.S., Pineda, J.A.
Brain metabolism and severe pediatric traumatic brain injury
(2017) Child's Nervous System, 33 (10), pp. 1719-1726. 

DOI: 10.1007/s00381-017-3514-y


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


Abstract
Age-dependent changes in brain metabolism may influence the response to and tolerance of secondary insults, potentially affecting outcomes. More complete characterization of brain metabolism across the clinical trajectory of severe pediatric TBI is needed to improve our ability to measure and better mitigate the impact of secondary insults. Better management of secondary insults will impact clinical care and the probability of success of future neuroprotective clinical trials. Improved bedside monitoring and imaging technologies will be required to achieve these goals. Effective and sustained integration of brain metabolism information into the pediatric critical care setting will be equally challenging and important. © 2017, Springer-Verlag GmbH Germany.


Author Keywords
Brain metabolism;  Secondary injury;  Traumatic brain injury


Document Type: Article
Source: Scopus

 

14) 

Janowski, A.B., Bauer, I.K., Holtz, L.R., Wang, D.
Propagation of astrovirus VA1, a neurotropic human astrovirus, in cell culture
(2017) Journal of Virology, 91 (19), art. no. e00740-17, . 

DOI: 10.1128/JVI.00740-17


a Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
b Department of Molecular Microbiology and Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Astrovirus VA1/HMO-C (VA1; mamastrovirus 9) is a recently discovered astrovirus genotype that is divergent from the classic human astroviruses (mamastrovirus 1). The gastrointestinal tract is presumed to be the primary site of infection and pathogenicity for astroviruses. However, VA1 has been independently detected in brain tissue of five cases of human encephalitis. Studies of the pathogenicity of VA1 are currently impossible because there are no reported cell culture systems or in vivo models that support VA1 infection. Here, we describe successful propagation of VA1 in multiple human cell lines. The initial inoculum, a filtered clinical stool sample from the index gastroenteritis case cluster that led to the discovery of VA1, was first passaged in Vero cells. Serial blind passage in Caco-2 cells yielded increasing copies of VA1 RNA, and multistep growth curves demonstrated a >100-fold increase in VA1 RNA 72 h after inoculation. The full-length genomic and subgenomic RNA strands were detected by Northern blotting, and crystalline lattices of viral particles of ~26-nm diameter were observed by electron microscopy in infected Caco-2 cells. Unlike other human astrovirus cell culture systems, which require addition of exogenous trypsin for continued propagation, VA1 could be propagated equally well with or without the addition of trypsin. Furthermore, VA1 was sensitive to the type I interferon (IFN-I) response, as VA1 RNA levels were reduced by pretreatment of Caco-2 cells with IFN-β1a. The ability to propagate VA1 in cell culture will facilitate studies of the neurotropism and neuropathogenesis of VA1. © 2017 American Society for Microbiology.


Author Keywords
Astrovirus;  Astrovirus VA1;  Cell culture;  Electron microscopy;  Encephalitis;  Pathogenesis;  Subgenomic RNA;  Viral propagation


Document Type: Article
Source: Scopus

 

15) 

Butler-Barnes, S.T., Varner, F., Williams, A., Sellers, R.
Academic Identity: A Longitudinal Investigation of African American Adolescents’ Academic Persistence
(2017) Journal of Black Psychology, 43 (7), pp. 714-739. 

DOI: 10.1177/0095798416683170


a Washington University in St. Louis, St. Louis, MO, United States
b University of Texas at Austin, Austin, TX, United States
c University of Michigan, Ann Arbor, MI, United States


Abstract
Adolescence is a vulnerable period for the development of academic identification and academic persistence, particularly among African American adolescents. The present study investigated how cultural assets (i.e., private regard and racial centrality) and academic assets (i.e., academic curiosity and academic self-esteem) influence African American adolescent boys’ (n = 109) and girls’ (n = 153) academic persistence over time. Additionally, we explored whether oppositional academic identity mediated the relationships between academic and cultural assets and academic persistence. Data were drawn from a cross-sectional longitudinal study. Results indicated significant direct effects of academic assets on academic persistence at Times 1 and 2 for boys and at Times 1, 2, and 3 for girls. Furthermore, oppositional academic identity mediated the relationship between boys’, but not girls’, cultural assets and academic persistence at Time 1. These findings have implications for understanding the role of assets in the lives of African American youth. © 2016, © The Author(s) 2016.


Author Keywords
academic identity;  academic persistence;  African American adolescents;  gender


Document Type: Article
Source: Scopus

 

16) 

Moore, J.R., Pollio, D.E., Hong, B.A., Valencia, C., Sorrell, M., North, C.S.
Pilot Design and Implementation of an Innovative Mental Health and Wellness Clinic at a Historically Black College/University
(2017) Community Mental Health Journal, pp. 1-5. Article in Press. 

DOI: 10.1007/s10597-017-0167-y


a Department of Psychiatry, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, United States
b Department of Social Work, College of Arts and Sciences, University of Alabama at Birmingham, HB 302E 1720 2nd Ave S, Birmingham, AL, United States
c Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8134, St. Louis, MO, United States
d Paul Quinn College, 3837 Simpson Stuart Rd, Dallas, TX, United States
e The Altshuler Center for Education & Research, Metrocare Services, 1250 Mockingbird Lane, Suite 330, Dallas, TX, United States
f The University of Texas Southwestern Medical Center, 6363 Forest Park Rd., Room BL6.226, Dallas, TX, United States


Abstract
A pilot mental health and wellness clinic was developed and implemented on the campus of Paul Quinn College, a small Historically Black College and University (HBCU) in Dallas, TX, to address mental health disparities in an African-American student population. Additionally, a series of student engagement activities was developed and implemented to address stigma and enhance linkage to the clinic. The student engagement activities were well attended. In all, 14 students requested a total of 97 appointments during the spring 2016 semester, but attended only 41 appointments. Students sought treatment of a variety of psychiatric disorders, most commonly major depressive disorder and adjustment disorder. A model based on this program could conceivably be extended to serve students more broadly in other HBCUs as well as in community colleges. © 2017 Springer Science+Business Media, LLC


Author Keywords
African American;  College mental health;  Health care disparities;  Historically Black College University;  Mental health assessment


Document Type: Article in Press
Source: Scopus

 

17) 

Oetjen, L.K., Mack, M.R., Feng, J., Whelan, T.M., Niu, H., Guo, C.J., Chen, S., Trier, A.M., Xu, A.Z., Tripathi, S.V., Luo, J., Gao, X., Yang, L., Hamilton, S.L., Wang, P.L., Brestoff, J.R., Council, M.L., Brasington, R., Schaffer, A., Brombacher, F., Hsieh, C.-S., Gereau, R.W., IV, Miller, M.J., Chen, Z.-F., Hu, H., Davidson, S., Liu, Q., Kim, B.S.
Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch
(2017) Cell, 171 (1), pp. 217-228.e13. 

DOI: 10.1016/j.cell.2017.08.006


a Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, United States
b Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
c Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States
e Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
f Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
g Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
h International Centre for Genetic Engineering and Biotechnology and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, University of Cape Town, Cape Town, South Africa


Abstract
Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior. © 2017 Elsevier Inc.


Author Keywords
atopic dermatitis;  IL-13;  IL-4;  IL-4Rα;  itch;  JAK1;  pruriceptor;  pruritus;  type 2 cytokines


Document Type: Article
Source: Scopus

 

18) 

Arriaga, M., Han, E.B.
Dedicated hippocampal inhibitory networks for locomotion and immobility
(2017) Journal of Neuroscience, 37 (38), pp. 9222-9238. 

DOI: 10.1523/JNEUROSCI.1076-17.2017


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


Abstract
Network activity is strongly tied to animal movement; however, hippocampal circuits selectively engaged during locomotion or immobility remain poorly characterized. Here we examined whether distinct locomotor states are encoded differentially in genetically defined classes of hippocampal interneurons. To characterize the relationship between interneuron activity and movement, we used in vivo, two-photon calcium imaging in CA1 of male and female mice, as animals performed a virtual-reality (VR) track running task. We found that activity in most somatostatin-expressing and parvalbumin-expressing interneurons positively correlated with locomotion. Surprisingly, nearly one in five somatostatin or one in seven parvalbumin interneurons were inhibited during locomotion and activated during periods of immobility. Anatomically, the somata of somatostatin immobility-activated neurons were smaller than those of movement-activated neurons. Furthermore, immobility-activated interneurons were distributed across cell layers, with somatostatin-expressing cells predominantly in stratum oriens and parvalbumin-expressing cells mostly in stratum pyramidale. Importantly, each cell’s correlation between activity and movement was stable both over time and across VR environments. Our findings suggest that hippocampal interneuronal microcircuits are preferentially active during either movement or immobility periods. These inhibitory networks may regulate information flow in “labeled lines” within the hippocampus to process information during distinct behavioral states. © 2017 the authors.


Author Keywords
Behavior;  Calcium imaging;  Circuits;  Hippocampus;  Interneurons;  Virtual reality


Document Type: Article
Source: Scopus

 

19) 

Mei, Y., Du, Z., Hu, C., Greenwald, N.F., Abedalthagafi, M., Agar, N.Y.R., Dunn, G.P., Bi, W.L., Santagata, S., Dunn, I.F.
Osteoglycin promotes meningioma development through downregulation of NF2 and activation of mTOR signaling
(2017) Cell Communication and Signaling, 15 (1), art. no. 34, . 

DOI: 10.1186/s12964-017-0189-7


a Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
b Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
c Department of Neurosurgery, Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, China
d Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
e Saudi Human Genome Laboratory, King Fahad Medical City, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia
f Department of Neurosurgery, Washington University, School of Medicine, St. Louis, MO, United States
g Center for Human Immunology and Immunotherapy Programs, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
Background: Meningiomas are the most common primary intracranial tumors in adults. While a majority of meningiomas are slow growing neoplasms that may cured by surgical resection, a subset demonstrates more aggressive behavior and insidiously recurs despite surgery and radiation, without effective alternative treatment options. Elucidation of critical mitogenic pathways in meningioma oncogenesis may offer new therapeutic strategies. We performed an integrated genomic and molecular analysis to characterize the expression and function of osteoglycin (OGN) in meningiomas and explored possible therapeutic approaches for OGN-expressing meningiomas. Methods: OGN mRNA expression in human meningiomas was assessed by RNA microarray and RNAscope. The impact of OGN on cell proliferation, colony formation, and mitogenic signaling cascades was assessed in a human meningioma cell line (IOMM-Lee) with stable overexpression of OGN. Furthermore, the functional consequences of introducing an AKT inhibitor in OGN-overexpressing meningioma cells were assessed. Results: OGN mRNA expression was dramatically increased in meningiomas compared to a spectrum of other brain tumors and normal brain. OGN-overexpressing meningioma cells demonstrated an elevated rate of cell proliferation, cell cycle activation, and colony formation as compared with cells transfected with control vector. In addition, NF2 mRNA and protein expression were both attenuated in OGN-overexpressing cells. Conversely, mTOR pathway and AKT activation increased in OGN-overexpressing cells compared to control cells. Lastly, introduction of an AKT inhibitor reduced OGN expression in meningioma cells and resulted in increased cell death and autophagy, suggestive of a reciprocal relationship between OGN and AKT. Conclusion: We identify OGN as a novel oncogene in meningioma proliferation. AKT inhibition reduces OGN protein levels in meningioma cells, with a concomitant increase in cell death, which provides a promising treatment option for meningiomas with OGN overexpression. © 2017 The Author(s).


Author Keywords
AKT inhibitor;  Autophagy;  Mammalian target of rapamycin complex 1;  Meningioma;  Neurofibromatosis type 2;  Osteoglycin


Document Type: Article
Source: Scopus

 

20) 

Rodgers, J.D., Lodi-Smith, J., Hill, P.L., Spain, S.M., Lopata, C., Thomeer, M.L.
Brief Report: Personality Mediates the Relationship between Autism Quotient and Well-Being: A Conceptual Replication using Self-Report
(2017) Journal of Autism and Developmental Disorders, pp. 1-9. Article in Press. 

DOI: 10.1007/s10803-017-3290-2


a Institute for Autism Research, Canisius College, Science Hall 1016B, 2001 Main St., Buffalo, NY, United States
b Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO, United States
c School of Management, Binghamton University, P. O. Box 6000, Vestal, NY, United States


Abstract
Autism spectrum disorder (ASD) impacts well-being across the lifespan. Individuals with ASD evidence differences in personality traits and self-concept clarity that are predictors of well-being in typically-developing individuals. The current research replicates a growing body of evidence demonstrating differences in well-being and personality between individuals low in ASD characteristics (n = 207) and individuals high in ASD characteristics (n = 46) collected from the general population using an online survey. Results were consistent in a subsample of demographically matched pairs (n = 39 per group) and relative to norms. Further, the current research provides the first evidence that openness, conscientiousness, emotional stability, and self-concept clarity mediate the relationship between ASD characteristics and well-being. © 2017 Springer Science+Business Media, LLC


Author Keywords
Autism spectrum disorder;  Personality traits;  Self-concept clarity;  Well-being


Document Type: Article in Press
Source: Scopus

 

21) 

Gray-Edwards, H.L., Jiang, X., Randle, A.N., Taylor, A.R., Voss, T.L., Johnson, A.K., McCurdy, V.J., Sena-Esteves, M., Ory, D.S., Martin, D.R.
Lipidomic Evaluation of Feline Neurologic Disease after AAV Gene Therapy
(2017) Molecular Therapy - Methods and Clinical Development, 6, pp. 135-142. 

DOI: 10.1016/j.omtm.2017.07.005


a Scott-Ritchey Research Center, Auburn University College of Veterinary Medicine, Auburn, AL, United States
b Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO, United States
c Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, AL, United States
d Department of Neurology, University of Massachusetts Medical School, Worcester, PA, United States
e Department of Anatomy, Physiology and Pharmacology Auburn University, Auburn, AL, United States
f Department of Biological Sciences, Mississippi State University, Starkville, MS, United States


Abstract
GM1 gangliosidosis is a fatal lysosomal disorder, for which there is no effective treatment. Adeno-associated virus (AAV) gene therapy in GM1 cats has resulted in a greater than 6-fold increase in lifespan, with many cats remaining alive at &gt;5.7 years of age, with minimal clinical signs. Glycolipids are the principal storage product in GM1 gangliosidosis whose pathogenic mechanism is not completely understood. Targeted lipidomics analysis was performed to better define disease mechanisms and identify markers of disease progression for upcoming clinical trials in humans. 36 sphingolipids and subspecies associated with ganglioside biosynthesis were tested in the cerebrospinal fluid of untreated GM1 cats at a humane endpoint (8 months), AAV-treated GM1 cats (5 years old), and normal adult controls. In untreated GM1 cats, significant alterations were noted in 16 sphingolipid species, including gangliosides (GM1 and GM3), lactosylceramides, ceramides, sphingomyelins, monohexosylceramides, and sulfatides. Variable degrees of correction in many lipid metabolites reflected the efficacy of AAV gene therapy. Sphingolipid levels were highly predictive of neurologic disease progression, with 11 metabolites having a coefficient of determination (R2) &gt; 0.75. Also, a specific detergent additive significantly increased the recovery of certain lipid species in cerebrospinal fluid samples. This report demonstrates the methodology and utility of targeted lipidomics to examine the pathophysiology of lipid storage disorders. © 2017 The Author(s)


Author Keywords
AAV;  adeno-associated virus;  biomarkers;  feline;  gene therapy;  GM1 gangliosidosis;  lipidomics;  neurologic disease


Document Type: Article
Source: Scopus

 

22) 

Cavazos-Rehg, P.A., Krauss, M.J., Sowles, S.J., Zewdie, K., Bierut, L.
Operating a motor vehicle after marijuana use: Perspectives from people who use high-potency marijuana
(2017) Substance Abuse, pp. 1-6. Article in Press. 

DOI: 10.1080/08897077.2017.1365802


Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA


Abstract
Background: With advancing marijuana legalization in the United States, a primary concern is the possible increase in consequences relating to marijuana driving impairment, especially among people who use high-potency marijuana (i.e., extracts). In this study, the research team assessed the risk perception and experiences of driving under the influence of marijuana by investigating people who use extracts. Methods: Participants from 2 studies were queried about driving after using marijuana. In Study 1, phone interviews (n = 19) were conducted with people who use extracts. In Study 2, people who use extracts (n = 174) were recruited to participate in a nationwide survey via an online existing panel. Responses to marijuana and driving–related questions were qualitatively coded for themes (e.g., riskiness, engagement in behavior) developed by the research team. Results: Prominent themes identified in Study 1 suggested a belief that driving risk following marijuana use is dependent on the individual (i.e., response/tolerance) or the amount/type of marijuana consumed. This theme was corroborated by Study 2 participants. Those who perceived no or minimal risk from driving following marijuana use were more likely to report engagement in driving following extracts use. Conclusions: More research is needed to understand how marijuana, especially in its concentrated form, impacts driving ability in order to develop appropriate and scientifically sound regulations. Such research could subsequently fill the need to improve and more widely disseminate prevention messages on marijuana use and driving risks. © 2017 Taylor & Francis Group, LLC


Author Keywords
Driving under the influence;  drugged driving;  impaired driving;  marijuana


Document Type: Article in Press
Source: Scopus

 

23) 

Bandara, N., Sharma, A.K., Krieger, S., Schultz, J.W., Han, B.H., Rogers, B.E., Mirica, L.M.
Evaluation of 64Cu-Based Radiopharmaceuticals that Target Aβ Peptide Aggregates as Diagnostic Tools for Alzheimer's Disease
(2017) Journal of the American Chemical Society, 139 (36), pp. 12550-12558. 

DOI: 10.1021/jacs.7b05937


a Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Chemistry, Washington University, One Brookings Drive, St. Louis, MO, United States
c Department of Radiation Oncology, Washington University, School of Medicine, St. Louis, MO, United States
d Hope Center for Neurological Disorders, Washington University, School of Medicine, St. Louis, MO, United States
e Department of Pharmacology, A.T. Still University of Health Sciences, Kirksville College of Osteopathic Medicine, Kirksville, MO, United States


Abstract
Positron emission tomography (PET) imaging agents that detect amyloid plaques containing amyloid beta (Aβ) peptide aggregates in the brain of Alzheimer's disease (AD) patients have been successfully developed and recently approved by the FDA for clinical use. However, the short half-lives of the currently used radionuclides 11C (20.4 min) and 18F (109.8 min) may limit the widespread use of these imaging agents. Therefore, we have begun to evaluate novel AD diagnostic agents that can be radiolabeled with 64Cu, a radionuclide with a half-life of 12.7 h, ideal for PET imaging. Described herein are a series of bifunctional chelators (BFCs), L1-L5, that were designed to tightly bind 64Cu and shown to interact with Aβ aggregates both in vitro and in transgenic AD mouse brain sections. Importantly, biodistribution studies show that these compounds exhibit promising brain uptake and rapid clearance in wild-type mice, and initial microPET imaging studies of transgenic AD mice suggest that these compounds could serve as lead compounds for the development of improved diagnostic agents for AD. © 2017 American Chemical Society.


Document Type: Article
Source: Scopus

 

24) 

Paul, R., Rhee, G., Baker, L.M., Vaida, F., Cooley, S.A., Ances, B.M.
Effort and neuropsychological performance in HIV-infected individuals on stable combination antiretroviral therapy
(2017) Journal of NeuroVirology, pp. 1-9. Article in Press. 

DOI: 10.1007/s13365-017-0557-5


a Department of Psychological Sciences, University of Missouri- St. Louis, St. Louis, United States
b Missouri Institute of Mental Health, St. Louis, United States
c Department of Neurology, Washington University in St. Louis, St. Louis, United States
d Department of Family Medicine and Public Health, Division of Biostatistics and Bio-informatics, University of California San Diego, San Diego, CA, United States
e Department of Neurology, Washington University in Saint Louis School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St. Louis, MO, United States


Abstract
The expression of cognitive symptoms associated with HIV varies over time and across individuals. This pattern may reflect transient contextual factors, including the degree of effort exerted by individuals undergoing cognitive testing. The present study examined whether effort corresponds to the expression of persistent HIV-related cognitive impairment among individuals receiving combination antiretroviral therapy (cART). HIV+ individuals (n = 111) averaged 48.2 (14.9) years of age and 13.0 (2.7) years of education and HIV− individuals (n = 92) averaged 34.9 (17.2) years of age and 13.5 (1.9) years of education. Participants completed a neuropsychological battery and a clinically validated measure of effort (Test of Memory Malingering, trial 1). Results revealed that the vast majority of HIV+ (85%) and HIV− (89%) individuals performed above published guidelines for adequate effort. Furthermore, the expression of cognitive impairment in HIV was not related to effort performance. The results were unchanged when examining HIV+ individuals with and without viral suppression. Finally, disability and disability-seeking status, and a proxy measure of apathy did not correspond to effort levels in HIV+ individuals. These findings suggest that variability in the expression of cognitive impairment in the cART era is unlikely to represent overt effort failures or other confounds unrelated to the disease. Persistent cognitive impairment in HIV likely represents historical and/or ongoing disease mechanisms despite otherwise successful treatment. © 2017 Journal of NeuroVirology, Inc.


Author Keywords
Cognition;  Effort;  HIV;  Neuropsychological performance;  Test of Memory Malingering (TOMM)


Document Type: Article in Press
Source: Scopus

 

25) 

Ouwenga, R., Lake, A.M., O’Brien, D., Mogha, A., Dani, A., Dougherty, J.D.
Transcriptomic analysis of ribosome-bound mRNA in cortical neurites in vivo
(2017) Journal of Neuroscience, 37 (36), pp. 8688-8705. 

DOI: 10.1523/JNEUROSCI.3044-16.2017


a Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
e Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
f Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Localized translation in neurites helps regulate synaptic strength and development. Dysregulation of local translation is associated with many neurological disorders. However, due to technical limitations, study of this phenomenon has largely been limited to brain regions with laminar organization of dendrites such as the hippocampus or cerebellum. It has not been examined in the cortex, a region of importance for most neurological disorders, where dendrites of each neuronal population are densely intermingled with cell bodies of others. Therefore, we have developed a novel method, SynapTRAP, which combines synaptoneurosomal fractionation with translating ribosome affinity purification to identify ribosome-bound mRNA in processes of genetically defined cell types. We demonstrate Synap-TRAP’s efficacy and report local translation in the cortex of mice, where we identify a subset of mRNAs that are translated in dendrites by neuronal ribosomes. These mRNAs have disproportionately longer lengths, enrichment for FMRP binding and G-quartets, and their genes are under greater evolutionary constraint in humans. In addition, we show that alternative splicing likely regulates this phenomenon. Overall, SynapTRAP allows for rapid isolation of cell-type-specific localized translation and is applicable to classes of previously inaccessible neuronal and non-neuronal cells in vivo. © 2017 the authors.


Author Keywords
Local translation;  Synaptic translation;  Synaptoneurosomes;  SynapTRAP;  TRAP


Document Type: Article
Source: Scopus

 

26) 

Caulfield, A.F., Flower, O., Pineda, J.A., Uddin, S.
Emergency Neurological Life Support: Acute Non-traumatic Weakness
(2017) Neurocritical Care, 27, pp. 29-50. 

DOI: 10.1007/s12028-017-0450-3


a Department of Neurology, Stanford University, Stanford, CA, United States
b Department of Intensive Care, Royal North Shore Hospital, Sydney, Australia
c Departments of Pediatrics and Neurology, Washington University School of Medicine at St. Louis, St. Louis, MO, United States
d Department of Critical Care Medicine, King’s College Hospital, London, United Kingdom


Abstract
Acute non-traumatic weakness may be life-threatening if it involves the respiratory muscles and/or is associated with autonomic dysfunction. Most patients presenting with acute muscle weakness have a worsening neurological disorder that requires a rapid, systematic evaluation and detailed neurological exam to localize the disorder. Urgent laboratory tests and neuroimaging are needed to confirm the diagnosis. Because acute weakness is a common presenting sign of neurological emergencies, it was chosen as an Emergency Neurological Life Support protocol. Causes of acute non-traumatic weakness are discussed here by both presenting clinical signs and anatomical location. For each diagnosis, key features of the history, examination, investigations, and treatment are outlined in the included tables or in the “Appendix”. © 2017, Neurocritical Care Society.


Author Keywords
Acute weakness;  Neuromuscular weakness;  Respiratory failure


Document Type: Article
Source: Scopus

 

27) 

Fehlings, M.G., Tetreault, L.A., Riew, K.D., Middleton, J.W., Wang, J.C.
A Clinical Practice Guideline for the Management of Degenerative Cervical Myelopathy: Introduction, Rationale, and Scope
(2017) Global Spine Journal, 7 (3_supplement), pp. 21S-27S. 

DOI: 10.1177/2192568217703088


a Toronto Western Hospital, University Health Network, Toronto, ON, Canada
b University of Toronto, Toronto, ON, Canada
c University College Cork, Cork, Ireland
d Washington University School of Medicine, St Louis, MO, United States
e Medical School, University of Sydney, Sydney, NSW, Australia
f University of Southern California, Los Angeles, CA, United States


Abstract
Degenerative cervical myelopathy (DCM) is a progressive spine disease and the most common cause of spinal cord dysfunction in adults worldwide. Patients with DCM may present with common signs and symptoms of neurological dysfunction, such as paresthesia, abnormal gait, decreased hand dexterity, hyperreflexia, increased tone, and sensory dysfunction. Clinicians across several specialties encounter patients with DCM, including primary care physicians, rehabilitation specialists, therapists, rheumatologists, neurologists, and spinal surgeons. Currently, there are no guidelines that outline how to best manage patients with mild (defined as a modified Japanese Orthopedic Association (mJOA) score of 15-17), moderate (mJOA = 12-14), or severe (mJOA ≤ 11) myelopathy, or nonmyelopathic patients with evidence of cord compression. This guideline provides evidence-based recommendations to specify appropriate treatment strategies for these populations. The intent of our recommendations is to (1) help identify patients at high risk of neurological deterioration, (2) define the role of nonoperative and operative management in each patient population, and (3) determine which patients are most likely to benefit from surgical intervention. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with DCM by promoting standardization of care and encouraging clinicians to make evidence-informed decisions. © 2017, © The Author(s) 2017.


Author Keywords
cervical spondylotic myelopathy;  degenerative cervical myelopathy;  guideline development;  guidelines


Document Type: Editorial
Source: Scopus

 

28) 

Meehan, T.P., Bressler, S.L., Tang, W., Astafiev, S.V., Sylvester, C.M., Shulman, G.L., Corbetta, M.
Top-down cortical interactions in visuospatial attention
(2017) Brain Structure and Function, 222 (7), pp. 3127-3145. 

DOI: 10.1007/s00429-017-1390-6


a Center for Complex Systems and Brain Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, United States
b Department of Psychology, Florida Atlantic University, Boca Raton, FL, United States
c Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Neurobiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The voluntary allocation of visuospatial attention depends upon top-down influences from the frontal eye field (FEF) and intraparietal sulcus (IPS)—the core regions of the dorsal attention network (DAN)—to visual occipital cortex (VOC), and has been further associated with within-DAN influences, particularly from the FEF to IPS. However, the degree to which these influences manifest at rest and are then modulated during anticipatory visuospatial attention tasks remains poorly understood. Here, we measured both undirected and directed functional connectivity (UFC, DFC) between the FEF, IPS, and VOC at rest and during an anticipatory visuospatial attention task, using a slow event-related design. Whereas the comparison between rest and task indicated FC modulations that persisted throughout the task duration, the large number of task trials we collected further enabled us to measure shorter timescale modulations of FC across the trial. Relative to rest, task engagement induced enhancement of both top-down influences from the DAN to VOC, as well as bidirectional influences between the FEF and IPS. These results suggest that task performance induces enhanced interaction within the DAN and a greater top-down influence on VOC. While resting FC generally showed right hemisphere dominance, task-related enhancement favored the left hemisphere, effectively balancing a resting hemispheric asymmetry, particularly within the DAN. On a shorter (within-trial) timescale, VOC-to-DAN and bidirectional FEF-IPS influences were transiently elevated during the anticipatory period of the trial, evincing phasic modulations related to changing attentional demands. In contrast to these task-specific effects, resting and task-related influence patterns were highly correlated, suggesting a predisposing role for resting organization, which requires minimal tonic and phasic modulations for control of visuospatial attention. © 2017, Springer-Verlag Berlin Heidelberg.


Author Keywords
Cognitive control;  Dorsal attention network;  Hemispheric asymmetry;  Intrinsic connectivity;  Task set


Document Type: Article
Source: Scopus

 

29) 

Ruzycki, P.A., Linne, C.D., Hennig, A.K., Chen, S.
Crx-L253x mutation produces dominant photoreceptor defects in TVRM65 mice
(2017) Investigative Ophthalmology and Visual Science, 58 (11), pp. 4644-4653. 

DOI: 10.1167/iovs.17-22075


a Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO, United States
b Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, MO, United States
c Department of Developmental Biology, Washington University, St. Louis, MO, United States


Abstract
PURPOSE. The cone-rod homeobox (CRX) transcription factor is essential for photoreceptor gene expression, differentiation, and survival. Human CRX mutations can cause dominant retinopathies of varying onset and phenotype severity. In animal models, dominant frameshift Crx mutations introduce a premature termination codon (PTC), producing inactive truncated proteins that interfere with normal CRX function. Previously, a mutant mouse, TVRM65, was reported to carry a recessive late PTC mutation, Crx-L253X. More detailed phenotype analysis of the pathogenicity of Crx-L253X sheds new light on the variability of CRX-linked diseases. METHODS. Homozygous (L253X/X); heterozygous (L253X/+); Crx-/- and control C57BL/6J (WT) mice were analyzed at various ages for changes in retinal function (ERG), morphology (histology) and photoreceptor gene expression (qRT-PCR). RESULTS. At 1 month, L253X/X mice lack visual function, show greater reductions in retinal thickness, and distinct gene expression changes relative to Crx-/-, suggesting that the phenotype of L253X/X is more severe than Crx-/-. L253X/+ mice have reduced rod/cone function, but normal retinal morphology at all ages tested. qRT-PCR assays described a complex phenotype in which both developing and mature photoreceptors are unable to maintain proper gene expression. L253X mRNA/protein is overexpressed relative to normal Crx, suggesting a pathogenic mechanism similar to early PTC mutations. However, the overexpression is less pronounced, correlating with a relatively mild dominant phenotype. CONCLUSIONS. The L253X mouse provides a valuable model for CRX-associated retinopathy. The pathogenicity of CRX frameshift mutations depends on the position of the PTC, which in turn determines the degree of mutant mRNA/protein overproduction. © 2017 The Authors.


Author Keywords
Animal models;  Cone-rod dystrophy;  CRX mutations;  Gene expression;  Inherited photoreceptor degeneration


Document Type: Article
Source: Scopus

 

30) 

Fowler, P.J., Farrell, A.F.
Housing and Child Well Being: Implications for Research, Policy, and Practice
(2017) American Journal of Community Psychology, 60 (1-2), pp. 3-8. 

DOI: 10.1002/ajcp.12154


a Washington University in St. Louis, St. Louis, MO, United States
b Chapin Hall at the University of Chicago, Chicago, IL, United States


Abstract
Inadequate housing and homelessness represent significant barriers to family stability and child development. An accumulating body of evidence documents the relatively high risk of family separation among families experiencing housing instability and homelessness, the extent of housing problems experienced by families involved in the child welfare system, and the disproportionately high rates of homelessness among youth aging out of foster care. Vulnerable youth and families interact frequently with various social service programs intended to mitigate multifaceted and multilevel risks, however, systems efforts and resources are rarely coordinated and results to date are mixed. We introduce 13 papers that are part of a burgeoning, increasingly sophisticated body of scholarship that inform coordinated responses to inadequate housing experienced by families involved in child welfare and related interventions. We note emergent themes and state a pressing need for research that accounts for ecological and contextual influences, examines the differential impact of housing and service interventions, identifies critical ingredients of effective housing and service interventions, and positions for scale-up. We distill findings into a set of observations and recommendations that align with best intentions to improve quality of life and promote well being among some of society's most vulnerable individuals. © Society for Community Research and Action 2017


Author Keywords
Child welfare;  Child well being;  Foster care;  Homelessness;  Housing


Document Type: Article
Source: Scopus

 

31) 

Fehlings, M.G., Tetreault, L.A., Riew, K.D., Middleton, J.W., Aarabi, B., Arnold, P.M., Brodke, D.S., Burns, A.S., Carette, S., Chen, R., Chiba, K., Dettori, J.R., Furlan, J.C., Harrop, J.S., Holly, L.T., Kalsi-Ryan, S., Kotter, M., Kwon, B.K., Martin, A.R., Milligan, J., Nakashima, H., Nagoshi, N., Rhee, J., Singh, A., Skelly, A.C., Sodhi, S., Wilson, J.R., Yee, A., Wang, J.C.
A Clinical Practice Guideline for the Management of Patients With Degenerative Cervical Myelopathy: Recommendations for Patients With Mild, Moderate, and Severe Disease and Nonmyelopathic Patients With Evidence of Cord Compression
(2017) Global Spine Journal, 7 (3_supplement), pp. 70S-83S. 

DOI: 10.1177/2192568217701914


a Toronto Western Hospital, University Health Network, Toronto, ON, Canada
b University of Toronto, Toronto, ON, Canada
c University College Cork, Cork, Ireland
d Washington University School of Medicine, St Louis, MO, United States
e University of Sydney, Sydney, NSW, Australia
f University of Maryland School of Medicine, Baltimore, MD, United States
g The University of Kansas, Kansas City, KS, United States
h University of Utah, Salt Lake City, UT, United States
i National Defense Medical College, Saitama, Japan
j Spectrum Research, Inc, Tacoma, WA, United States
k Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada
l Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, United States
m University of California at Los Angeles, Los Angeles, CA, United States
n University of Cambridge, Cambridge, United Kingdom
o Vancouver General Hospital, Vancouver, BC, Canada
p The Centre for Family Medicine, Kitchener, ON, Canada
q Department of Family Medicine, McMaster University, Hamilton, ON, Canada
r Western University, London, ON, Canada
s Nagoya University Graduate School of Medicine, Nagoya, Japan
t Keio University School of Medicine, Keio, Japan
u Emory University, Atlanta, GA, United States
v Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, ON, Canada
w Sunnybrook Health Sciences Centre, Toronto, ON, Canada
x USC Spine Center, Los Angeles, CA, United States


Abstract
Study Design: Guideline development. Objectives: The objective of this study is to develop guidelines that outline how to best manage (1) patients with mild, moderate, and severe myelopathy and (2) nonmyelopathic patients with evidence of cord compression with or without clinical symptoms of radiculopathy. Methods: Five systematic reviews of the literature were conducted to synthesize evidence on disease natural history; risk factors of disease progression; the efficacy, effectiveness, and safety of nonoperative and surgical management; the impact of preoperative duration of symptoms and myelopathy severity on treatment outcomes; and the frequency, timing, and predictors of symptom development. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the management of degenerative cervical myelopathy (DCM). Results: Our recommendations were as follows: (1) “We recommend surgical intervention for patients with moderate and severe DCM.” (2) “We suggest offering surgical intervention or a supervised trial of structured rehabilitation for patients with mild DCM. If initial nonoperative management is pursued, we recommend operative intervention if there is neurological deterioration and suggest operative intervention if the patient fails to improve.” (3) “We suggest not offering prophylactic surgery for non-myelopathic patients with evidence of cervical cord compression without signs or symptoms of radiculopathy. We suggest that these patients be counseled as to potential risks of progression, educated about relevant signs and symptoms of myelopathy, and be followed clinically.” (4) “Non-myelopathic patients with cord compression and clinical evidence of radiculopathy with or without electrophysiological confirmation are at a higher risk of developing myelopathy and should be counselled about this risk. We suggest offering either surgical intervention or nonoperative treatment consisting of close serial follow-up or a supervised trial of structured rehabilitation. In the event of myelopathic development, the patient should be managed according to the recommendations above.” Conclusions: These guidelines will promote standardization of care for patients with DCM, decrease the heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions. © 2017, © The Author(s) 2017.


Author Keywords
cervical spondylotic myelopathy;  degenerative cervical myelopathy;  guidelines;  spinal cord compression


Document Type: Article
Source: Scopus

 

32) 

Huang, H., Zhu, C.-T., Skuja, L.L., Hayden, D.J., Hart, A.C.
Genome-Wide screen for genes involved in Caenorhabditis elegans developmentally timed sleep
(2017) G3: Genes, Genomes, Genetics, 7 (9), pp. 2907-2917. 

DOI: 10.1534/g3.117.300071


a Department of Neuroscience and Evolutionary Biology, Brown University, Providence, RI, United States
b Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, United States
c Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
d Trait and Pipeline Delivery Analytics, Monsanto Research Center, Chesterfield, MO, United States
e Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States


Abstract
In Caenorhabditis elegans, Notch signaling regulates developmentally timed sleep during the transition from L4 larval stage to adulthood (L4/A) . To identify core sleep pathways and to find genes acting downstream of Notch signaling, we undertook the first genome-wide, classical genetic screen focused on C. elegans developmentally timed sleep. To increase screen efficiency, we first looked for mutations that suppressed inappropriate anachronistic sleep in adult hsp::osm-11 animals overexpressing the Notch coligand OSM-11 after heat shock. We retained suppressor lines that also had defects in L4/A developmentally timed sleep, without heat shock overexpression of the Notch coligand. Sixteen suppressor lines with defects in developmentally timed sleep were identified. One line carried a new allele of goa-1; loss of GOA-1 Gαo decreased C. elegans sleep. Another line carried a new allele of gpb-2, encoding a Gβ5 protein; Gβ5 proteins have not been previously implicated in sleep. In other scenarios, Gβ5 GPB-2 acts with regulators of G protein signaling (RGS proteins) EAT-16 and EGL-10 to terminate either EGL-30 Gαq signaling or GOA-1 Gαo signaling, respectively. We found that loss of Gβ5 GPB-2 or RGS EAT-16 decreased L4/A sleep. By contrast, EGL-10 loss had no impact. Instead, loss of RGS-1 and RGS-2 increased sleep. Combined, our results suggest that, in the context of L4/A sleep, GPB-2 predominantly acts with EAT-16 RGS to inhibit EGL- 30 Gαq signaling. These results confirm the importance of G protein signaling in sleep and demonstrate that these core sleep pathways function genetically downstream of the Notch signaling events promoting sleep. © 2017 Huang et al.


Author Keywords
C. elegans;  G protein;  GOA-1;  GPB-2;  Mutant Screen;  Report;  Screen;  Sleep


Document Type: Article
Source: Scopus

 

33) 

Rubenstein, R., Chang, B., Yue, J.K., Chiu, A., Winkler, E.A., Puccio, A.M., Diaz-Arrastia, R., Yuh, E.L., Mukherjee, P., Valadka, A.B., Gordon, W.A., Okonkwo, D.O., Davies, P., Agarwal, S., Lin, F., Sarkis, G., Yadikar, H., Yang, Z., Manley, G.T., Wang, K.K.W., Cooper, S.R., Dams-O’Connor, K., Borrasso, A.J., Inoue, T., Maas, A.I.R., Menon, D.K., Schnyer, D.M., Vassar, M.J.
Comparing plasma phospho tau, total tau, and phospho tau–total tau ratio as acute and chronic traumatic brain injury biomarkers
(2017) JAMA Neurology, 74 (9), pp. 1063-1072. Cited 1 time.

DOI: 10.1001/jamaneurol.2017.0655


a Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, United States
b Department of Neurological Surgery, University of California, San Francisco, United States
c Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
d Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
e Department of Psychology, Washington University, St Louis, MO, United States
f Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium
g Departments of Anesthesia and Neurocritical Care, University of Cambridge, Cambridge, United Kingdom
h Department of Psychology, University of Texas, Austin, United States
i Laboratory of Neurodegenerative Diseases and CNS Biomarker Discovery, Departments of Neurology and Physiology/Pharmacology, State University of New York Downstate Medical Center, Brooklyn, United States
j Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, United States
k Department of Neurological Surgery, University of California, San Francisco, United States
l Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
m University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
n Department of Radiology, University of California, San Francisco, United States
o Department of Neurosurgery, Virginia Commonwealth University, Richmond, United States
p Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
q Litwin-Zucker Center for Research in Alzheimer’s Disease, Feinstein Institute for Medical Research, Manhasset, NY, United States
r Department of Orthopedic Surgery and Rehabilitation Medicine, State University of New York Downstate Medical Center, Brooklyn, United States
s Program for Neurotrauma, Neuroproteomics, and Biomarker Research, Department of Emergency Medicine, Psychiatry and Chemistry, University of Florida, Gainesville, United States
t Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, Alexandria, Egypt
u Department of Biochemistry, Kuwait University, Khadiya, Kuwait


Abstract
IMPORTANCE: Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. OBJECTIVE: To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. DESIGN, SETTING, AND PARTICIPANTS: In the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (<24 hours after injury) and 21 patients with TBI admitted to inpatient rehabilitation units (mean [SD], 176.4 [44.5] days after injury). Control samples were purchased from a commercial vendor. The TRACK-TBI Pilot study was conducted from April 1, 2010, to June 30, 2012. Data analysis for the current investigation was performed from August 1, 2015, to March 13, 2017. MAIN OUTCOMES AND MEASURES: Plasma samples were assayed for P-tau (using an antibody that specifically recognizes phosphothreonine-231) and T-tau using ultra-high sensitivity laser-based immunoassay multi-arrayed fiberoptics conjugated with rolling circle amplification. RESULTS: In the 217 patients with TBI, 161 (74.2%) were men; mean (SD) age was 42.5 (18.1) years. The P-tau and T-tau levels and P-tau–T-tau ratio in patients with acute TBI were higher than those in healthy controls. Receiver operating characteristic analysis for the 3 tau indices demonstrated accuracy with area under the curve (AUC) of 1.000, 0.916, and 1.000, respectively, for discriminating mild TBI (Glasgow Coma Scale [GCS] score, 13-15, n = 162) from healthy controls. The P-tau level and P-tau–T-tau ratio were higher in individuals with more severe TBI (GCS, ≤12 vs 13-15). The P-tau level and P-tau–T-tau ratio outperformed the T-tau level in distinguishing cranial computed tomography–positive from -negative cases (AUC = 0.921, 0.923, and 0.646, respectively). Acute P-tau levels and P-tau–T-tau ratio weakly distinguished patients with TBI who had good outcomes (Glasgow Outcome Scale–Extended GOS-E, 7-8) (AUC = 0.663 and 0.658, respectively) and identified those with poor outcomes (GOS-E, ≤4 vs >4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau–T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively). CONCLUSIONS AND RELEVANCE: Plasma P-tau levels and P-tau–T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau–T-tau ratios show more robust and sustained elevations among patients with chronic TBI. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

34) 

O'Callaghan, C.
Sensing, the Senses, and Attention
(2017) Philosophy and Phenomenological Research, 95 (2), pp. 485-491. 

DOI: 10.1111/phpr.12412


Washington University in St. Louis, United States


Document Type: Conference Paper
Source: Scopus

 

35) 

Cadena, R., Shoykhet, M., Ratcliff, J.J.
Emergency Neurological Life Support: Intracranial Hypertension and Herniation
(2017) Neurocritical Care, 27, pp. 82-88. 

DOI: 10.1007/s12028-017-0454-z


a Departments of Neurology, Neurosurgery, and Emergency Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
b Pediatric Critical Care Medicine, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
c Departments of Emergency Medicine and Neurology, Emory University, Atlanta, GA, United States


Abstract
Sustained intracranial hypertension and acute brain herniation are “brain codes,” signifying catastrophic neurological events that require immediate recognition and treatment to prevent irreversible injury and death. As in cardiac arrest, a brain code mandates the organized implementation of a stepwise management algorithm. The goal of this Emergency Neurological Life Support protocol is to implement an evidence-based, standardized approach to the evaluation and management of patients with intracranial hypertension and/or herniation. © 2017, Neurocritical Care Society.


Author Keywords
Emergency Neurological Life Support;  Intracranial hypertension;  Intracranial pressure;  Neurocritical care


Document Type: Article
Source: Scopus

 

36) 

Peters, C.H., Yu, A., Zhu, W., Silva, J.R., Ruben, P.C.
Depolarization of the conductance-voltage relationship in the NaV1.5 mutant, E1784K, is due to altered fast inactivation
(2017) PLoS ONE, 12 (9), art. no. e0184605, . 

DOI: 10.1371/journal.pone.0184605


a Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
b Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States


Abstract
E1784K is the most common mixed long QT syndrome/Brugada syndrome mutant in the cardiac voltage-gated sodium channel NaV1.5. E1784K shifts the midpoint of the channel conductance-voltage relationship to more depolarized membrane potentials and accelerates the rate of channel fast inactivation. The depolarizing shift in the midpoint of the conductance curve in E1784K is exacerbated by low extracellular pH. We tested whether the E1784K mutant shifts the channel conductance curve to more depolarized membrane potentials by affecting the channel voltage-sensors. We measured ionic currents and gating currents at pH 7.4 and pH 6.0 in Xenopus laevis oocytes. Contrary to our expectation, the movement of gating charges is shifted to more hyperpolarized membrane potentials by E1784K. Voltage-clamp fluorimetry experiments show that this gating charge shift is due to the movement of the DIVS4 voltage-sensor being shifted to more hyperpolarized membrane potentials. Using a model and experiments on fast inactivation-deficient channels, we show that changes to the rate and voltage-dependence of fast inactivation are sufficient to shift the conductance curve in E1784K. Our results localize the effects of E1784K to DIVS4, and provide novel insight into the role of the DIV-VSD in regulating the voltage-dependencies of activation and fast inactivation. © 2017 Peters et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Document Type: Article
Source: Scopus

 

37) 

Brophy, G.M., Human, T.
Pharmacotherapy Pearls for Emergency Neurological Life Support
(2017) Neurocritical Care, 27, pp. 51-73. 

DOI: 10.1007/s12028-017-0456-x


a Departments of Pharmacotherapy and Outcomes Science and Neurosurgery, Virginia Commonwealth University, Richmond, VA, United States
b Department of Clinical Pharmacy, Barnes-Jewish Hospital, Washington University in St. Louis, St. Louis, MO, United States


Abstract
The appropriate use of medications during Emergency Neurological Life Support (ENLS) is essential to optimize patient care. Important considerations when choosing the appropriate agent include the patient’s organ function and medication allergies, potential adverse drug effects, drug interactions and critical illness and aging pathophysiologic changes. Critical medications used during ENLS include hyperosmolar therapy, anticonvulsants, antithrombotics, anticoagulant reversal and hemostatic agents, anti-shivering agents, neuromuscular blockers, antihypertensive agents, sedatives, vasopressors and inotropes, and antimicrobials. This article focuses on the important pharmacokinetic and pharmacodynamics characteristics, advantages and disadvantages and clinical pearls of these therapies, providing practitioners with essential drug information to optimize pharmacotherapy in acutely ill neurocritical care patients. © 2017, Neurocritical Care Society.


Author Keywords
Adverse drug event;  Drug interaction;  ENLS;  Medication;  Pharmacotherapy


Document Type: Article
Source: Scopus

 

38) 

Fowler, P.J., Farrell, A.F., Marcal, K.E., Chung, S., Hovmand, P.S.
Housing and Child Welfare: Emerging Evidence and Implications for Scaling up Services
(2017) American Journal of Community Psychology, 60 (1-2), pp. 134-144. Cited 1 time.

DOI: 10.1002/ajcp.12155


a Washington University in St. Louis, St. Louis, MO, United States
b Chapin Hall, University of Chicago, Chicago, United States


Abstract
Inadequate housing threatens family stability in communities across the United States. This study reviews emerging evidence on housing interventions in the context of scale-up for the child welfare system. In child welfare, scale-up refers to the extent to which fully implemented interventions sustainably alleviate family separations associated with housing instability. It incorporates multiple aspects beyond traditional measures of effectiveness including costs, potential reach, local capacities for implementation, and fit within broader social services. The framework further encompasses everyday circumstances faced by service providers, program administrators, and policymakers who allocate resources under conditions of scarcity and uncertainty. The review of current housing interventions reveals a number of systemic constraints for scale-up in child welfare. Reliance on rental assistance programs limits capacity to address demand, while current practices that target the most vulnerable families may inadvertently diminish effectiveness of the intervention and increase overall demand. Alternative approaches that focus on homelessness prevention and early intervention must be tested in conjunction with community initiatives to increase accessibility of affordable housing. By examining system performance over time, the scalability framework provides an opportunity for more efficient coordination of housing services within and outside of the child welfare system. © Society for Community Research and Action 2017


Author Keywords
Child welfare;  Evidence-based interventions;  Homelessness;  Homelessness prevention;  Scale-up;  Systems science


Document Type: Article
Source: Scopus

 

39) 

Tetreault, L.A., Rhee, J., Prather, H., Kwon, B.K., Wilson, J.R., Martin, A.R., Andersson, I.B., Dembek, A.H., Pagarigan, K.T., Dettori, J.R., Fehlings, M.G.
Change in Function, Pain, and Quality of Life Following Structured Nonoperative Treatment in Patients With Degenerative Cervical Myelopathy: A Systematic Review
(2017) Global Spine Journal, 7 (3_supplement), pp. 42S-52S. 

DOI: 10.1177/2192568217700397


a Toronto Western Hospital, University Health Network, Toronto, ON, Canada
b University College Cork, Cork, Ireland
c Emory University, Atlanta, GA, United States
d Washington University, St Louis, MO, United States
e Vancouver General Hospital, Vancouver, BC, Canada
f University of Toronto, Toronto, ON, Canada
g University of Puget Sound, Tacoma, WA, United States
h Spectrum Research, Inc, Tacoma, WA, United States


Abstract
Study Design: Systematic review. Objectives: The objective of this study was to conduct a systematic review to determine (1) change in function, pain, and quality of life following structured nonoperative treatment for degenerative cervical myelopathy (DCM); (2) variability of change in function, pain, and quality of life following different types of structured nonoperative treatment; (3) differences in outcomes observed between certain subgroups (eg, baseline severity score, duration of symptoms); and (4) negative outcomes and harms resulting from structured nonoperative treatment. Methods: A systematic search was conducted in Embase, PubMed, and the Cochrane Collaboration for articles published between January 1, 1950, and February 9, 2015. Studies were included if they evaluated outcomes following structured nonoperative treatment, including therapeutic exercise, manual therapy, cervical bracing, and/or traction. The quality of each study was evaluated using the Newcastle-Ottawa Scale, and strength of the overall body of evidence was rated using guidelines outlined by the Grading of Recommendation Assessment, Development and Evaluation Working Group. Results: Of the 570 retrieved citations, 8 met inclusion criteria and were summarized in this review. Based on our results, there is very low evidence to suggest that structured nonoperative treatment for DCM results in either a positive or negative change in function as evaluated by the Japanese Orthopaedic Association score. Conclusion: There is a lack of evidence to determine the role of nonoperative treatment in patients with DCM. However, in the majority of studies, patients did not achieve clinically significant gains in function following structured nonoperative treatment. Furthermore, 23% to 54% of patients managed nonoperatively subsequently underwent surgical treatment. © 2017, © The Author(s) 2017.


Author Keywords
cervical spondylotic myelopathy;  degenerative cervical myelopathy;  nonoperative treatment;  systematic review


Document Type: Review
Source: Scopus

 

40) 

D’Souza, R.D., Burkhalter, A.
A laminar organization for selective cortico-cortical communication
(2017) Frontiers in Neuroanatomy, 11, art. no. 71, . 

DOI: 10.3389/fnana.2017.00071


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


Abstract
The neocortex is central to mammalian cognitive ability, playing critical roles in sensory perception, motor skills and executive function. This thin, layered structure comprises distinct, functionally specialized areas that communicate with each other through the axons of pyramidal neurons. For the hundreds of such cortico-cortical pathways to underlie diverse functions, their cellular and synaptic architectures must differ so that they result in distinct computations at the target projection neurons. In what ways do these pathways differ? By originating and terminating in different laminae, and by selectively targeting specific populations of excitatory and inhibitory neurons, these “interareal” pathways can differentially control the timing and strength of synaptic inputs onto individual neurons, resulting in layer-specific computations. Due to the rapid development in transgenic techniques, the mouse has emerged as a powerful mammalian model for understanding the rules by which cortical circuits organize and function. Here we review our understanding of how cortical lamination constrains long-range communication in the mammalian brain, with an emphasis on the mouse visual cortical network. We discuss the laminar architecture underlying interareal communication, the role of neocortical layers in organizing the balance of excitatory and inhibitory actions, and highlight the structure and function of layer 1 in mouse visual cortex. © 2017 D’Souza and Burkhalter.


Author Keywords
Cortical hierarchy;  Cortical inhibition;  Interareal communication;  Layer 1;  Mouse visual cortex


Document Type: Article
Source: Scopus

 

41) 

Zhang, M., Chen, Y.
Weisfeiler-lehman neural machine for link prediction
(2017) Proceedings of the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, Part F129685, pp. 575-583. 

DOI: 10.1145/3097983.3097996


Department of Computer Science and Engineering, Washington University, St. Louis, United States


Abstract
In this paper, we propose a next-generation link prediction method, Weisfeiler-Lehman Neural Machine (WLNM), which learns topo-logical features in the form of graph patterns that promote the formation of links. WLNM has unmatched advantages including higher performance than state-of-the-art methods and universal applicability over various kinds of networks. WLNM extracts an enclosing subgraph of each target link and encodes the subgraph as an adjacency matrix. The key novelty of the encoding comes from a fast hashing-based Weisfeiler-Lehman (WL) algorithm that labels the vertices according to their structural roles in the subgraph while preserving the subgraph's intrinsic directionality. After that, a neural network is trained on these adjacency matrices to learn a predictive model. Compared with traditional link prediction methods, WLNM does not assume a particular link formation mechanism (such as common neighbors), but learns this mechanism from the graph itself. We conduct comprehensive experiments to show that WLNM not only outperforms a great number of state-of-the-art link prediction methods, but also consistently performs well across networks with different characteristics. © 2017 Association for Computing Machinery.


Author Keywords
Color refinement;  Graph labeling;  Link prediction;  Neural network


Document Type: Conference Paper
Source: Scopus

 

42) 

Yao, Z., Zhu, Z., Chen, Y.
Atrial fibrillation detection by multi-scale convolutional neural networks
(2017) 20th International Conference on Information Fusion, Fusion 2017 - Proceedings, art. no. 8009782, . 

DOI: 10.23919/ICIF.2017.8009782


a Beijing Advanced Innovation Center for Future Internet Technology, Beijing University of Technology, Beijing, China
b Department of Computer Science and Engineering, Washington University in St. Louis, United States


Abstract
Atrial Fibrillation (AF) is the most common chronic arrhythmia. Effective detection of the AF would avoid serious consequences like stroke. Conventional AF detection methods need heuristic or hand-craft feature extraction. In this paper, A deep neural network named multi-scale convolutional neural networks (MCNN) based AF detector is proposed. Instant heart rate sequence is extracted from ECG signal, then an end-to-end MCNN detects AF with the instant heart rate sequence as input and detection result as output. The algorithm was tested on both public and private datasets. On the public dataset, with the sensitivity achieved being 0.9822, the corresponding specificity is 0.9811, and the overall accuracy is 0.9818. The area under an ROC curve is as high as 0.9962, compared to the AUC of the best conventional method is 0.9947. Comparison shows that the MCNN based AF detector give superior accuracy than conventional methods. Test on private dataset also shows significant improvement. © 2017 International Society of Information Fusion (ISIF).


Document Type: Conference Paper
Source: Scopus

 

43) 

Carlozzi, N.E., Goodnight, S., Casaletto, K.B., Goldsmith, A., Heaton, R.K., Wong, A.W.K., Baum, C.M., Gershon, R., Heinemann, A.W., Tulsky, D.S.
Validation of the NIH Toolbox in Individuals with Neurologic Disorders
(2017) Archives of Clinical Neuropsychology, 32 (5), pp. 555-573. 

DOI: 10.1093/arclin/acx020


a Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, United States
b Department of Neurology, University of California, San Francisco, CA, United States
c Center for Rehabilitation Outcomes Research, Rehabilitation Institute of Chicago, Chicago, IL, United States
d Department of Psychiatry, University of California San Diego, San Diego, CA, United States
e Occupational Therapy and Department of Neurology, Washington University, St. LouisMO, United States
f Department of Medical Social Sciences, Northwestern University, Chicago, IL, United States
g Department of Preventative Medicine, Northwestern University, Chicago, IL, United States
h Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg, School of Medicine, Chicago, IL, United States
i Department of Physical Therapy, Center for Assessment Research and Translation, University of Delaware, Newark, DE, United States
j Kessler Foundation, West OrangeNJ, United States


Abstract
Individuals with spinal cord injury (SCI), traumatic brain injury (TBI), and stroke experience a variety of neurologically related deficits across multiple domains of function. The NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) examines motor, sensation, cognition, and emotional functioning. The purpose of this paper is to establish the validity of the NIHTB in individuals with neurologic conditions. Methods Community-dwelling individuals with SCI (n = 209), TBI (n = 184), or stroke (n = 211) completed the NIHTB. Relative risks for impaired performance were examined relative to a matched control groups. Results The largest group differences were observed on the Motor domain and for the Fluid Cognition measures. All groups were at increased risk for motor impairment relative to normative standards and matched controls. Fluid cognitive abilities varied across groups such that individuals with stroke and TBI performed more poorly than individuals with SCI; increased relative risks for impaired fluid cognition were seen for individuals in the stroke and TBI groups, but not for those in the SCI group. All three neurologic groups performed normally on most measures in the Sensation Battery, although TBI participants evidenced increased risk for impaired odor identification and the stroke group showed more vision difficulties. On the Emotion Battery, participants in all three groups showed comparably poor psychological well-being, social satisfaction, and self-efficacy, whereas the TBI group also evidenced slightly increased negative affect. Conclusions Data provide support for the validity of the NIHTB in individuals with neurologic conditions. © 2017 The Author.


Author Keywords
Assessment;  Cognition;  Disability;  Emotion;  Motor;  NIHTB;  Outcomes assessment (health care);  Sensory;  Spinal cord injury;  Stroke;  Traumatic brain injury


Document Type: Article
Source: Scopus

 

44) 

Klein, R.S., Hunter, C.A.
Protective and Pathological Immunity during Central Nervous System Infections
(2017) Immunity, 46 (6), pp. 891-909. 

DOI: 10.1016/j.immuni.2017.06.012


a Departments of Medicine, Pathology and Immunology, Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA
b Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA


Abstract
The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege. Copyright © 2017. Published by Elsevier Inc.


Author Keywords
astrocyte;  blood brain barrier;  Brain;  central nervous system;  encephalitis;  infection;  meningitis;  monocyte;  neuron;  T cell


Document Type: Review
Source: Scopus

 

45) 

Kim, D.H., Dacey, R.G., Zipfel, G.J., Berger, M.S., McDermott, M., Barbaro, N.M., Shapiro, S.A., Solomon, R.A., Harbaugh, R., Day, A.L.
Neurosurgical Education in a Changing Healthcare and Regulatory Environment: A Consensus Statement from 6 Programs
(2017) Neurosurgery, 80 (4), pp. S75-S82. 

DOI: 10.1093/neuros/nyw146


a Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, Texas
b Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri
c Department of Neurological Surgery, University of California, San Francisco, San Francisco, California
d Department of Neurosurgery, Indiana University, Indianapolis, Indiana
e Department of Neurosurgery, Columbia University, New York, New York
f Department of Neurosurgery, Pennsylvania State University, Hershey, Pennsylvania


Abstract
The purpose of neurosurgical education is to teach the clinical knowledge and surgical skills necessary to become a neurosurgeon. Another goal is to inculcate the principles of the scientific method. However, increasing expectations about attending involvement during surgery, duty hour requirements, and new curricular mandates have put programs under stress to ensure adequate training, in less time, in an environment of limited resident independence. More recently, the Accreditation Council for Graduate Medical Education has developed a new tracking process based on "milestones" or defined educational outcomes. At the same time, our healthcare system is undergoing a rapid socioeconomic transition in organization and payment models, which traditionally has not been a focus of formal teaching. A 2008 survey conducted by the Council of State Neurosurgical Societies found that graduating residents felt inadequately prepared in areas like contract negotiation, practice evaluation, and management. Copyright © 2017 by the Congress of Neurological Surgeons.


Author Keywords
Neurosurgery residency;  Neurosurgical education;  Neurosurgical milestones


Document Type: Article
Source: Scopus

 

46) 

Olson, D.W.M., Parcon, C., Santos, A., Santos, G., Delabar, R., Stutzman, S.E.
A novel approach to explore how nursing care affects intracranial pressure
(2017) American Journal of Critical Care, 26 (2), pp. 136-139. 

DOI: 10.4037/ajcc2017410


a Neurology and therapeutics, Dallas, TX, United States
b University of Texas Southwestern Medical Center, Dallas, TX, United States
c Baylor University Medical Center, Dallas, TX, United States
d Texas Woman's University, Denton, TX, United States
e Washington University, St Louis, MO, United States


Abstract
Background Intracranial pressure is measured continuously, and nursing behaviors have been associated with variations in the measurements. Methods A prospective pilot observational study was done to develop a comprehensive list of nursing behaviors that affect patients' intracranial pressure. Data on nurses were obtained by self-reports and video recording. Patient-level data were collected via chart abstraction, video recording, and patients' monitors. Results Data on 9 patients and 32 nurses were analyzed. A total of 6244 minutes of data were video recorded. Intracranial pressure was changed because of a nursing intervention during 3394 observations. Compared with baseline levels, intracranial pressure was significantly higher if a nursing intervention was performed (odds ratio, 1.96; 95% CI, 1.71-2.24; P < .001). Conclusion Studying nursing behaviors is feasible. Synchronizing and analyzing mutually exclusive and exhaustive behaviors indicated that nursing behaviors have an effect on patients' intracranial pressure. © 2017 American Association of Critical-Care Nurses.


Document Type: Article
Source: Scopus

 

47) 

Power, J.D., Laumann, T.O., Plitt, M., Martin, A., Petersen, S.E.
On Global fMRI Signals and Simulations
(2017) Trends in Cognitive Sciences, . Article in Press. 

DOI: 10.1016/j.tics.2017.09.002


a Sackler Institute, Department of Psychiatry, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY 10065, USA
b Department of Psychiatry, Washington University School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA
c Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA
d National Institute of Mental Health, Bethesda, MD 20814, USA
e Departments of Neurology and Psychology, Washington University School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA


Document Type: Article in Press
Source: Scopus

 

48) 

Scott-Wittenborn, N., Karadaghy, O.A., Piccirillo, J.F., Peelle, J.E.
A methodological assessment of studies that use voxel-based morphometry to study neural changes in tinnitus patients
(2017) Hearing Research, . Article in Press. 

DOI: 10.1016/j.heares.2017.09.002


Department of Otolaryngology - Head and Neck Surgery, Washington University School of Medicine, Saint Louis, MO, USA


Abstract
Background: The scientific understanding of tinnitus and its etiology has transitioned from thinking of tinnitus as solely a peripheral auditory problem to an increasing awareness that cortical networks may play a critical role in tinnitus percept or bother. With this change, studies that seek to use structural brain imaging techniques to better characterize tinnitus patients have become more common. These studies include using voxel-based morphometry (VBM) to determine if there are differences in regional gray matter volume in individuals who suffer from tinnitus and those who do not. However, studies using VBM in patients with tinnitus have produced inconsistent and sometimes contradictory results. Objective: This paper is a systematic review of all of the studies to date that have used VBM to study regional gray matter volume in people with tinnitus, and explores ways in which methodological differences in these studies may account for their heterogeneous results. We also aim to provide guidance on how to conduct future studies using VBM to produce more reproducible results to further our understanding of disease processes such as tinnitus. Methods: Studies about tinnitus and VBM were searched for using PubMed and Embase. These returned 15 and 25 results respectively. Of these, nine met the study criteria and were included for review. An additional 5 studies were identified in the literature as pertinent to the topic at hand and were added to the review, for a total of 13 studies. Results: There was significant heterogeneity among the studies in several areas, including inclusion and exclusion criteria, software programs, and statistical analysis. We were not able to find publicly shared data or code for any study. Discussion: The differences in study design, software analysis, and statistical methodology make direct comparisons between the different studies difficult. Especially problematic are the differences in the inclusion and exclusion criteria of the study, and the statistical design of the studies, both of which could radically alter findings. Thus, heterogeneity has complicated efforts to explore the etiology of tinnitus using structural MRI. Conclusion: There is a pressing need to standardize the use of VBM when evaluating tinnitus patients. While some heterogeneity is expected given the rapid advances in the field, more can be done to ensure that there is internal validity between studies. © 2017 Elsevier B.V.


Author Keywords
Gray matter;  Magnetic resonance imaging;  Tinnitus;  Voxel-based morphometry


Document Type: Article in Press
Source: Scopus

 

49) 

Swanson, M.R., Shen, M.D., Wolff, J.J., Elison, J.T., Emerson, R.W., Styner, M.A., Hazlett, H.C., Truong, K., Watson, L.R., Paterson, S., Marrus, N., Botteron, K.N., Pandey, J., Schultz, R.T., Dager, S.R., Zwaigenbaum, L., Estes, A.M., Piven, J.
Subcortical Brain and Behavior Phenotypes Differentiate Infants With Autism Versus Language Delay
(2017) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, . Article in Press. 

DOI: 10.1016/j.bpsc.2017.07.007


a Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
b Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
c Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
d Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
e Division of Speech and Hearing Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
f Department of Educational Psychology, University of Minnesota, Minneapolis, Minnesota
g Institute of Child Development, University of Minnesota, Minneapolis, Minnesota
h Department of Psychology, Temple University
i Center for Autism Research at the Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania
j Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
k Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri
l Department of Radiology, University of Washington, Seattle, Washington
m Department of Speech and Hearing Sciences, University of Washington, Seattle, Washington
n Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada


Abstract
Background: Younger siblings of children with autism spectrum disorder (ASD) are themselves at increased risk for ASD and other developmental concerns. It is unclear if infants who display developmental concerns, but are unaffected by ASD, share similar or dissimilar behavioral and brain phenotypes to infants with ASD. Most individuals with ASD exhibit heterogeneous difficulties with language, and their receptive-expressive language profiles are often atypical. Yet, little is known about the neurobiology that contributes to these language difficulties. Methods: In this study, we used behavioral assessments and structural magnetic resonance imaging to investigate early brain structures and associations with later language skills. High-risk infants who were later diagnosed with ASD (n = 86) were compared with high-risk infants who showed signs of early language delay (n = 41) as well as with high- and low-risk infants who did not have ASD or language delay (n = 255 and 143, respectively). Results: Results indicated that diminished language skills were evident at 12 months in infants with ASD and infants with early language delay. At 24 months of age, only the infants with ASD displayed atypical receptive-expressive language profiles. Associations between 12-month subcortical volumes and 24-month language skills were moderated by group status, indicating disordinal brain-behavior associations among infants with ASD and infants with language delay. Conclusions: These results suggest that there are different brain mechanisms influencing language development in infants with ASD and infants with language delay, and that the two groups likely experience unique sets of genetic and environmental risk factors. © 2017 Society of Biological Psychiatry.


Author Keywords
ASD;  Brain;  Infancy;  Language delay;  Language profile;  Subcortical structure


Document Type: Article in Press
Source: Scopus

 

50) 

Liégeois, R., Laumann, T.O., Snyder, A.Z., Zhou, J., Yeo, B.T.T.
Interpreting temporal fluctuations in resting-state functional connectivity MRI
(2017) NeuroImage, . Article in Press. 

DOI: 10.1016/j.neuroimage.2017.09.012


a Department of Electrical and Computer Engineering, ASTAR-NUS Clinical Imaging Research Centre, Singapore Institute for Neurotechnology and Memory Networks Program, National University of Singapore, Singapore
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
c Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
d Centre for Cognitive Neuroscience, Duke-NUS Medical School, Singapore
e Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA


Abstract
Resting-state functional connectivity is a powerful tool for studying human functional brain networks. Temporal fluctuations in functional connectivity, i.e., dynamic functional connectivity (dFC), are thought to reflect dynamic changes in brain organization and non-stationary switching of discrete brain states. However, recent studies have suggested that dFC might be attributed to sampling variability of static FC. Despite this controversy, a detailed exposition of stationarity and statistical testing of dFC is lacking in the literature. This article seeks an in-depth exploration of these statistical issues at a level appealing to both neuroscientists and statisticians.We first review the statistical notion of stationarity, emphasizing its reliance on ensemble statistics. In contrast, all FC measures depend on sample statistics. An important consequence is that the space of stationary signals is much broader than expected, e.g., encompassing hidden markov models (HMM) widely used to extract discrete brain states. In other words, stationarity does not imply the absence of brain states. We then expound the assumptions underlying the statistical testing of dFC. It turns out that the two popular frameworks - phase randomization (PR) and autoregressive randomization (ARR) - generate stationary, linear, Gaussian null data. Therefore, statistical rejection can be due to non-stationarity, nonlinearity and/or non-Gaussianity. For example, the null hypothesis can be rejected for the stationary HMM due to nonlinearity and non-Gaussianity. Finally, we show that a common form of ARR (bivariate ARR) is susceptible to false positives compared with PR and an adapted version of ARR (multivariate ARR).Application of PR and multivariate ARR to Human Connectome Project data suggests that the stationary, linear, Gaussian null hypothesis cannot be rejected for most participants. However, failure to reject the null hypothesis does not imply that static FC can fully explain dFC. We find that first order AR models explain temporal FC fluctuations significantly better than static FC models. Since first order AR models encode both static FC and one-lag FC, this suggests the presence of dynamical information beyond static FC. Furthermore, even in subjects where the null hypothesis was rejected, AR models explain temporal FC fluctuations significantly better than a popular HMM, suggesting the lack of discrete states (as measured by resting-state fMRI). Overall, our results suggest that AR models are not only useful as a means for generating null data, but may be a powerful tool for exploring the dynamical properties of resting-state fMRI. Finally, we discuss how apparent contradictions in the growing dFC literature might be reconciled. •Space of stationary models bigger than expected; includes hidden Markov model (HMM).•Phase & autoregressive randomizations test for stationarity, linearity, Gaussianity.•Resting-state fMRI is mostly stationary, linear, and Gaussian.•1st order autoregressive (AR) model encodes static & one-lag FC.•1st order AR model explains sliding window correlations very well, better than HMM. © 2017 Elsevier Inc.


Author Keywords
Autoregressive model;  Brain states;  Dynamic FC;  Linear dynamical systems;  Stationarity;  Surrogate data


Document Type: Article in Press
Source: Scopus

 

51) 

Lenze, E.J., Stark, S., Avidan, M.S.
Alternative Facts? Antidepressants and Falls in Older Adults
(2017) American Journal of Geriatric Psychiatry, . Article in Press. 

DOI: 10.1016/j.jagp.2017.07.017


Department of Psychiatry, Washington University, St Louis, MO


Document Type: Article in Press
Source: Scopus

 

52) 

Burkhalter, A.
The network for intracortical communication in mouse visual cortex
(2016) Research and Perspectives in Neurosciences, (9783319277769), pp. 31-43. 

DOI: 10.1007/978-3-319-27777-6_4


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


Abstract
New techniques for identifying cell types, tracing their synaptic partners, imaging and manipulating their activity in behaving organisms have made mice a widely used model for linking brain circuits to behavior. Most behaviors are tied to vision: identifying objects, guiding movements of body parts, navigating through the environment, and even social interactions. Reason enough to focus on the mouse visual cortex. To find our way around in the occipital cortex, we needed a map. We took a classic approach and traced in the same animal the outputs from multiple retinotopic sites of primary visual cortex (V1) and compared the relative location of projections in the extrastriate cortex. We found nine extrastriate maps and showed by single unit recordings that each of the connectional maps contained visually responsive neurons whose receptive fields were mapped in orderly fashion and completely covered the visual field. Remarkably, a tiny region of one sixth of a dime contained a two- to three-times larger number of areas than the highly developed somatosensory and auditory cortices. By tracing the connections, we found that each of the ten visual areas projected to 25–35 cortical targets and interconnected virtually all of the areas reciprocally with one another. Although the binary graph density of the connection matrix was nearly complete, the connection strengths between areas within the ventral and dorsal cortex differed, indicating that the information from V1 flowed into distinct but interconnected streams. Unit recordings and calcium imaging studies showed that the ventral and dorsal streams processed different spatiotemporal information, which aligned with known properties of streams in primates. Analyses of the laminar patterns of interareal projections showed that areas were organized at multiple levels, suggesting that each stream represented a processing hierarchy. © 2016, The Author(s).


Document Type: Book Chapter
Source: Scopus