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

Neuroscience Publications Archive - May 2017

Weekly Scopus Report

May 29, 2017

May 22, 2017

May 15, 2017

May 1, 2017

 

May 29, 2017

1) 

Weinstock, J.a , April, L.M.a , Kallmi, S.b 
Is subclinical gambling really subclinical?
(2017) Addictive Behaviors, 73, pp. 185-191. 

DOI: 10.1016/j.addbeh.2017.05.014


a Saint Louis University, United States
b Washington University in St. Louis, United States


Abstract
Gambling disorder and substance use disorders (SUD) overlap in terms of etiology and diagnostic constructs (e.g., preoccupation, loss of control), yet diagnostic thresholds for the disorders are different. Currently, endorsing 2–3 gambling disorder criteria does not warrant a diagnosis while endorsing 2–3 SUD criteria does. The aim of this study was to examine whether subclinical gamblers (i.e., endorsing 2–3 gambling disorder criteria) experience psychosocial dysfunction equivalent to individuals who are diagnosed with mild severity SUD (i.e., 2–3 SUD criteria) and whether this level of dysfunction is significantly different from individuals with no psychopathology. Data are from the first wave of Quinte Longitudinal Study, a large epidemiological sample (N = 4121). Psychometrically supported measures assessed for psychosocial functioning and the presence of Axis-I psychiatric disorders. Cross-sectional analysis examined 7 domains of psychosocial functioning using ANCOVA, which allowed for the inclusion of covariates, to test for difference between subclinical gamblers and individuals with no psychopathology and individuals with mild severity SUD. Equivalency testing compared subclinical gamblers in relation to mild severity SUD. Subclinical gamblers reported significantly poorer psychosocial functioning in relation to individuals endorsing no current psychopathology. Subclinical gamblers were also equivalent to and not significantly different from individuals with mild severity SUD. Subclinical gamblers experience similar psychosocial impairment to those individuals who endorse mild severity SUD, and this significantly differed from healthy individuals. The threshold for diagnosis of gambling disorder therefore warrants re-examination. © 2017 Elsevier Ltd


Author Keywords
Diagnostic threshold;  Equivalence testing;  Gambling disorder;  Substance use disorders


Document Type: Article
Source: Scopus

 

2) 

Ermel, J.a , Carter, C.S.b , Gold, J.M.c , MacDonald, A.W., IIId e , Daniel Ragland, J.b , Silverstein, S.M.f , Strauss, M.E.g , Barch, D.M.a h 
Self versus informant reports on the specific levels of functioning scale: Relationships to depression and cognition in schizophrenia and schizoaffective disorder
(2017) Schizophrenia Research: Cognition, 9, pp. 1-7. 

DOI: 10.1016/j.scog.2017.04.001


a Department of Psychological & Brain Science, Washington University, Box 1125, One Brookings Drive, St. Louis, MO, United States
b University of California at Davis, Imaging Research Center, 4701 X Street, Sacramento, CA, United States
c Maryland Psychiatric Research Center, Dept of Psychiatry, University of Maryland Baltimore, PO Box 21247, Baltimore, MD, United States
d Department of Psychology, University of Minnesota, Minneapolis, MN, United States
e Department of Psychiatry, University of Minnesota School of Medicine, 75 E. River Rd, Minneapolis, MN, United States
f Rutgers University, Department of Psychiatry, 671 Hoes Lane West, Piscataway, NJ, United States
g Case Western Reserve University, PO Box 3837, Corrales, NM, United States
h Department of Psychiatry, Washington University, Box 1125, One Brookings Drive, St. Louis, MO, United States


Abstract
The goal of the current study was to examine the relationships between insight and both cognitive function and depression in schizophrenia and schizoaffective disorder, and to determine if there were similar relationships across diagnostic categories. We examined discrepancies between self and informant reports of function on the Specific levels of function scale as a metric of insight for interpersonal, social acceptance, work and activities. We examined two samples of individuals with schizophrenia and/or schizoaffective disorder (Ns of 188 and 67 respectively). In Sample 1, cognition was measured using the Dot Probe Expectancy Task. In Sample 2, cognition was measured by averaging several subtests from the MATRICS consensus cognitive battery, as well as additional measures of working memory. In both samples, depression was measured using the Brief Psychiatric Rating Scale. In both samples, we found significant relationships between worse cognition and overestimations of work function, as well as between higher depression levels and underestimation of interpersonal function. These relationships were specific to interpersonal and work function, with significantly stronger correlations with interpersonal and work function compared to the other areas of function. Similar results were found across diagnostic categories. These results have important implications for treatment planning, as they suggest the need to take into account depression and cognitive function when evaluating the patient's self-report of function, and highlight the utility of informant reports in evaluating function and treatment planning. Further, they add to the literature on the similarity across schizophrenia and schizoaffective disorder in a variety of pathological mechanisms. © 2017 The Authors


Author Keywords
Cognition;  Depression;  Function;  Insight;  Interpersonal;  Psychosis


Document Type: Article
Source: Scopus

 

3) 

Ben-David, V., Jonson-Reid, M.
Resilience among adult survivors of childhood neglect: A missing piece in the resilience literature
(2017) Children and Youth Services Review, 78, pp. 93-103. 

DOI: 10.1016/j.childyouth.2017.05.014


Brown School of Social Work, Washington University in St. Louis, Campus Box 1196, One Brookings Drive, St. Louis, MO, United States


Abstract
Despite the established long-term effect of childhood maltreatment, some proportion of adult individuals, who suffered childhood maltreatment, appear more resilient than others and continue to function well in life. We searched the databases of MEDLINE, PsycINFO and ERIC in order to identify relevant studies on resilience among adult survivors of child neglect, which constitutes the most common form of child maltreatment. We found that the vast majority of quantitative (n = 41) and qualitative (n = 45) studies on resilience among adult survivors focused on survivors of sexual and physical abuse rather than neglect. Only few studies examined neglect often along with other forms of child maltreatment. We reviewed the studies, identified gaps in the existing literature, and suggested directions for future research. © 2017


Author Keywords
Adult resilience;  Adult survivors of child neglect;  Child neglect;  Childhood maltreatment


Document Type: Article
Source: Scopus

 

4) 

Kerekes, N.a , Falk, Ö.b , Brändström, S.c , Anckarsäter, H.b , Råstam, M.d e , Hofvander, B.d 
The protective effect of character maturity in child aggressive antisocial behavior
(2017) Comprehensive Psychiatry, 76, pp. 129-137. 

DOI: 10.1016/j.comppsych.2017.04.007


a Department of Health Sciences, University West, Trollhättan, Sweden
b Centre for Ethics, Law and Mental health (CELAM), University of Gothenburg, Sweden
c Center for Well-being Washington University, School of Medicine in St. Louis, United States
d Department of Clinical Sciences, Lund, Child and Adolescent Psychiatry, Lund University, Sweden
e Gillberg Neuropsychiatry Centre, University of Gothenburg, Sweden


Abstract
Background Childhood aggressive antisocial behavior (CD) is one of the strongest predictors of mental health problems and criminal behavior in adulthood. The aims of this study were to describe personality profiles in children with CD, and to determine the strength of association between defined neurodevelopmental symptoms, dimensions of character maturity and CD. Methods A sample of 1886 children with a close to equal distribution of age (9 or 12) and gender, enriched for neurodevelopmental and psychiatric problems were selected from the nationwide Child and Adolescent Twin Study in Sweden. Their parents rated them according to the Junior Temperament and Character Inventory following a telephone interview during which information about the children's development and mental health was assessed with the Autism-Tics, AD/HD and other Comorbidities inventory. Result Scores on the CD module significantly and positively correlated with scores on the Novelty Seeking temperament dimension and negatively with scores on character maturity (Self-Directedness and Cooperativeness). In the group of children with either neurodevelopmental or behavioral problems, the prevalence of low or very low character maturity was 50%, while when these two problems coexisted the prevalence of low or very low character maturity increased to 70%. Neurodevelopmental problems (such as: oppositional defiant disorder, symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder) and low scores on character maturity emerged as independently significant predictors of CD; in a multivariable model, only oppositional defiant symptoms and impulsivity significantly increased the risk for coexisting CD while a mature self-agency in a child (Self-Directedness) remained a significant protective factor. Conclusion These results suggest that children's willpower, the capacity to achieve personally chosen goals may be an important protective factor – even in the presence of neurodevelopmental and psychiatric problems – against progressing into persistent negative outcomes, such as aggressive antisocial behaviors. © 2017 Elsevier Inc.


Author Keywords
Character;  Child aggressive antisocial behavior;  Conduct disorder;  Mental health;  Neurodevelopment;  Personality;  Self-directedness


Document Type: Article
Source: Scopus

 

5) 

Satoh, A.a d , Imai, S.-I.a , Guarente, L.b c 
The brain, sirtuins, and ageing
(2017) Nature Reviews Neuroscience, 18 (6), pp. 362-374. 

DOI: 10.1038/nrn.2017.42


a Department of Developmental Biology, Washington University, School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St. Louis, MO, United States
b Department of Biology, Paul F. Glenn Center for the Science of Aging, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, United States
c Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA, United States
d National Center for Geriatrics and Gerontology, Sleep and Aging Regulation, Research Project Team, 7-430 Morioka-cho, Obu, Aichi, Japan


Abstract
In mammals, recent studies have demonstrated that the brain, the hypothalamus in particular, is a key bidirectional integrator of humoral and neural information from peripheral tissues, thus influencing ageing both in the brain and at the 'systemic' level. CNS decline drives the progressive impairment of cognitive, social and physical abilities, and the mechanisms underlying CNS regulation of the ageing process, such as microglia-neuron networks and the activities of sirtuins, a class of NAD + -dependent deacylases, are beginning to be understood. Such mechanisms are potential targets for the prevention or treatment of age-associated dysfunction and for the extension of a healthy lifespan.


Document Type: Review
Source: Scopus

 

6) 

Kim, T.a b , Kerschensteiner, D.a c d e 
Inhibitory Control of Feature Selectivity in an Object Motion Sensitive Circuit of the Retina
(2017) Cell Reports, 19 (7), pp. 1343-1350. 

DOI: 10.1016/j.celrep.2017.04.060


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, MO, United States
b Graduate Program in Neuroscience, Washington University School of Medicine, Saint Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO, United States
d Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO, United States
e Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO, United States


Abstract
Object motion sensitive (OMS) W3-retinal ganglion cells (W3-RGCs) in mice respond to local movements in a visual scene but remain silent during self-generated global image motion. The excitatory inputs that drive responses of W3-RGCs to local motion were recently characterized, but which inhibitory neurons suppress W3-RGCs’ responses to global motion, how these neurons encode motion information, and how their connections are organized along the excitatory circuit axis remains unknown. Here, we find that a genetically identified amacrine cell (AC) type, TH2-AC, exhibits fast responses to global motion and slow responses to local motion. Optogenetic stimulation shows that TH2-ACs provide strong GABAA receptor-mediated input to W3-RGCs but only weak input to upstream excitatory neurons. Cell-type-specific silencing reveals that temporally coded inhibition from TH2-ACs cancels W3-RGC spike responses to global but not local motion stimuli and, thus, controls the feature selectivity of OMS signals sent to the brain. © 2017 The Author(s)


Author Keywords
amacrine cell;  feature selectivity;  object motion;  retina;  surround inhibition;  temporal coding


Document Type: Article
Source: Scopus

 

7) 

Ray, W.Z.a , Mahan, M.A.b , Guo, D.c , Guo, D.c , Kliot, M.d 
An update on addressing important peripheral nerve problems: challenges and potential solutions
(2017) Acta Neurochirurgica, pp. 1-9. Article in Press. 

DOI: 10.1007/s00701-017-3203-3


a Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurosurgery, University of Utah, Salt Lake City, UT, United States
c BayCare Clinic, Green Bay, WI, United States
d Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, CA, United States


Abstract
From time to time it is thoughtful and productive to review a medical field and reflect upon what are the major issues that need to be addressed and what is being done to do so. This review article is not meant to be all-inclusive but rather focuses on four evolving areas in the field of peripheral nerve disorders and treatments: (1) nerve surgery under ultrasound guidance using a new ultra-minimally invasive thread technique; (2) evolving magnetic resonance imaging (MRI) and ultrasound imaging techniques that are helping to both diagnose and treat a variety of peripheral nerve problems including entrapment neuropathies, traumatic nerve injuries, and masses arising from nerves; (3) promoting recovery after nerve injury using electrical stimulation; and (4) developing animal models to reproduce a severe nerve injury (neurotmetic grade in continuity) that requires a surgical intervention and repair. In each area we first describe the current challenges and then discuss new and emerging techniques and approaches. It is our hope that this article will bring added attention and resources to help better address peripheral nerve problems that remain a challenge for both patients and physicians. © 2017 Springer-Verlag Wien


Author Keywords
Carpal tunnel;  Diffusion tensor imaging;  Peripheral nerve;  Regeneration


Document Type: Article in Press
Source: Scopus

 

8) 

Sakers, K.a b c , Lake, A.M.b c , Khazanchi, R.b c , Ouwenga, R.a b c , Vasek, M.J.b c , Dani, A.d e , Dougherty, J.D.b c e 
Astrocytes locally translate transcripts in their peripheral processes
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (19), pp. E3830-E3838. 

DOI: 10.1073/pnas.1617782114


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


Abstract
Local translation in neuronal processes is key to the alteration of synaptic strength necessary for long-term potentiation, learning, and memory. Here, we present evidence that regulated de novo protein synthesis occurs within distal, perisynaptic astrocyte processes. Astrocyte ribosomal proteins are found adjacent to synapses in vivo, and immunofluorescent detection of peptide elongation in acute slices demonstrates robust translation in distal processes. We have also developed a biochemical approach to define candidate transcripts that are locally translated in astrocyte processes. Computational analyses indicate that astrocyte-localized translation is both sequence-dependent and enriched for particular biological functions, such as fatty acid synthesis, and for pathways consistent with known roles for astrocyte processes, such as GABA and glutamate metabolism. These transcripts also include glial regulators of synaptic refinement, such as Sparc. Finally, the transcripts contain a disproportionate amount of a binding motif for the quaking RNA binding protein, a sequence we show can significantly regulate mRNA localization and translation in the astrocytes. Overall, our observations raise the possibility that local production of astrocyte proteins may support microscale alterations of adjacent synapses.


Author Keywords
Astrocyte;  Local translation;  RNA-sequencing;  Synapse;  TRAP


Document Type: Article
Source: Scopus

 

9) 

Chheda, M.G.a b , Gutmann, D.H.b 
Using Epigenetic Reprogramming to Treat Pediatric Brain Cancer
(2017) Cancer Cell, 31 (5), pp. 609-611. 

DOI: 10.1016/j.ccell.2017.04.008


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


Abstract
In this issue of Cancer Cell, Nagaraja et al. dissect the molecular mechanisms underlying therapeutic responses to transcriptional disruptors in the fatal pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). Moreover, they identify super-enhancers mediating these effects, highlighting how normal brain developmental programs can be hijacked in cancer. © 2017 Elsevier Inc.


Document Type: Short Survey
Source: Scopus

 

10) 

Pal, P.a b , Balaban, A.E.c d , DIamond, M.S.a b e , Sinnis, P.c d , Klein, R.S.a e f , Goldberg, D.E.a b 
Plasmodium falciparum histidine-rich protein II causes vascular leakage and exacerbates experimental cerebral malaria in mice
(2017) PLoS ONE, 12 (5), art. no. e0177142, . 

DOI: 10.1371/journal.pone.0177142


a Department of Medicine, Division of Infectious Diseases, Washington University, School of Medicine, St Louis, MO, United States
b Department of Molecular Microbiology, Washington University, School of Medicine, St Louis, MO, United States
c Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
d Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
e Department of Pathology and Immunology, 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
A devastating complication of Plasmodium falciparum infection is cerebral malaria, in which vascular leakage and cerebral swelling lead to coma and often death. P. falciparum produces a protein called histidine-rich protein II (HRPII) that accumulates to high levels in the bloodstream of patients and serves as a diagnostic and prognostic marker for falciparum malaria. Using a human cerebral microvascular endothelial barrier model, we previously found that HRPII activates the endothelial cell inflammasome, resulting in decreased integrity of tight junctions and increased endothelial barrier permeability. Here, we report that intravenous administration of HRPII induced blood-brain barrier leakage in uninfected mice. Furthermore, HRPII infusion in P. berghei-infected mice increased early mortality from experimental cerebral malaria. These data support the hypothesis that HRPII is a virulence factor that contributes to cerebral malaria by compromising the integrity of the blood-brain barrier. © 2017 Pal 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

 

11) 

Hill, P.L.a , Payne, B.R.b 
Don't forget the person when promoting healthy cognitive aging: Comment on Smith (2016)
(2017) American Psychologist, 72 (4), pp. 390-392. 

DOI: 10.1037/amp0000105


a Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
b Department of Psychology and Beckman Institute, University of Illinois at Urbana-Champaign, United States


Abstract
Smith (2016) provided a valuable review on healthy cognitive aging, addressing potential risk factors for dementia, as well as multiple mechanisms for preventing dementia. However, missing in this discussion was an acknowledgment of the potential that personality may play in shaping trajectories of cognitive aging. The current response provides a brief review of the ever accruing evidence that our dispositional traits and self-efficacy beliefs can predict trajectories of cognitive aging, as well as the mechanisms that produce these trajectories, including participants' likelihood to adhere to intervention efforts to reduce cognitive decline. We conclude by presenting recommendations for how cognitive aging researchers and practitioners can integrate personality science into their work. © 2017 American Psychological Association.


Author Keywords
Cognitive aging;  Healthy aging;  Memory self-efficacy;  Personality


Document Type: Note
Source: Scopus

 

12) 

Allison, S.a , Head, D.b 
Route repetition and route reversal: Effects of age and encoding method
(2017) Psychology and Aging, 32 (3), pp. 220-231. 

DOI: 10.1037/pag0000170


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


Abstract
Previous research indicates age-related impairments in learning routes from a start location to a target destination. There is less research on age effects on the ability to reverse a learned path. The method used to learn routes may also influence performance. This study examined how encoding methods influence the ability of younger and older adults to recreate a route in a virtual reality environment in forward and reverse directions. Younger (n = 50) and older (n = 50) adults learned a route either by self-navigation through the virtual environment or through studying a map. At test, participants recreated the route in the forward and reverse directions. Older adults in the map study condition had greater difficulty learning the route in the forward direction compared to younger adults. Older adults who learned the route by self-navigation were less accurate in traversing the route in the reverse compared to forward direction after a delay. In contrast, for older adults who learned via map study there were no significant differences between forward and reverse directions. Results suggest that older adults may not as readily develop and retain a sufficiently flexible representation of the environment during self-navigation to support accurate route reversal. Thus, initially learning a route from a map may be more difficult for older adults, but may ultimately be beneficial in terms of better supporting the ability to return to a start location. © 2017 American Psychological Association.


Author Keywords
Allocentric;  Cognitive map;  Egocentric;  Hippocampus;  Response learning


Document Type: Article
Source: Scopus

 

13) 

King, A.A.a , Seidel, K.b , Di, C.b , Leisenring, W.M.b , Perkins, S.M.a , Krull, K.R.c , Sklar, C.A.d , Green, D.M.c , Armstrong, G.T.c , Zeltzer, L.K.e , Wells, E.f , Stovall, M.g , Ullrich, N.J.h , Oeffinger, K.C.d , Robison, L.L.c , Packer, R.J.f 
Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma/PNET: A report from the Childhood Cancer Survivor Study
(2017) Neuro-Oncology, 19 (5), pp. 689-698. 

DOI: 10.1093/neuonc/now242


a Washington University School of Medicine, Siteman Cancer Center, St. Louis Children's Hospital, Barnes Jewish Hospital, Box 8505 660 South Euclid, St. Louis, MO, United States
b Fred Hutchinson Cancer Research Center, Seattle, WA, United States
c St. Jude Children's Research Hospital, Memphis, TN, United States
d Memorial Sloan Kettering Cancer Center, New York, NY, United States
e Mattel Children's Hospital, University of California Los Angeles, Los Angeles, CA, United States
f Children's National Health System, Washington, DC, United States
g University of Texas MD Anderson Cancer Center, Houston, TX, United States
h Boston Children's Hospital, Boston, MA, United States


Abstract
Background. Medulloblastoma is the most common malignant childhood brain tumor, although long-term risks for chronic neurologic health and psychosocial functioning in aging adult survivors are incompletely characterized. Methods. The Childhood Cancer Survivor Study (CCSS) includes 380 fve-year survivors of medulloblastoma/primitive neuroectodermal tumor (PNET; median age at follow-up: 30 y, interquartile range 24-36) and sibling comparison (n = 4031). Cumulative incidence of neurologic health conditions was reported. Cox regression models provided hazard ratios (HRs) and 95% CIs. Cross-sectional outcomes were assessed using generalized linear models. Results. Compared with siblings, survivors were at increased risk of late-onset hearing loss (HR: 36.0, 95% CI: 23.6-54.9), stroke (HR: 33.9, 95% CI: 17.8-64.7), seizure (HR: 12.8, 95% CI: 9.0-18.1), poor balance (HR: 10.4, 95% CI: 6.7-15.9), tinnitus (HR: 4.8, 95% CI: 3.5-6.8), and cataracts (HR: 31.8, 95% CI: 16.7-60.5). Temporal/frontal lobe radiotherapy of 50 Gy or more increased risk for hearing loss (HR: 1.9, 95% CI: 1.1-1.3), seizure (HR: 2.1, 95% CI: 1.1-3.9), stroke (HR: 3.5, 95% CI: 1.3-9.1), and tinnitus (HR: 2.0, 95% CI: 1.0-3.9). Survivors were less likely than siblings to earn a college degree (relative risk [RR]: 0.49, 95% CI: 0.39-0.60), marry (RR: 0.35, 95% CI: 0.29-0.42), and live independently (RR: 0.58, 95% CI: 0.52-0.66). Conclusions. Adult survivors of childhood medulloblastoma/PNET demonstrate pronounced risk for hearing impairment, stroke, lower educational attainment, and social independence. Interventions to support survivors should be a high priority. © 2017 The Author.


Author Keywords
Late effects;  Medulloblastoma;  Neurologic outcomes;  Psychosocial outcomes


Document Type: Article
Source: Scopus

 

14) 

Brown, B.M.a b c , Sohrabi, H.R.b c , Taddei, K.b c , Gardener, S.L.b c , Rainey-Smith, S.R.b c , Peiffer, J.J.a , Xiong, C.d , Fagan, A.M.e , Benzinger, T.f , Buckles, V.e , Erickson, K.I.g , Clarnette, R.h , Shah, T.c , Masters, C.L.i , Weiner, M.j , Cairns, N.k , Rossor, M.l , Graff-Radford, N.R.m , Salloway, S.n , Vöglein, J.o p , Laske, C.q r , Noble, J.s , Schofield, P.R.t u , Bateman, R.J.e , Morris, J.C.e , Martins, R.N.b c 
Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer's disease
(2017) Alzheimer's and Dementia, . Article in Press. 

DOI: 10.1016/j.jalz.2017.03.008


a School of Psychology and Exercise Science, Murdoch University, Murdoch, Western Australia, Australia
b Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
c McCusker Alzheimer's Research Foundation, Nedlands, Western Australia, Australia
d Division of Biostatistics, Washington University in St Louis, St Louis, Missouri, USA
e Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA
f Department of Radiology, Washington University in St Louis, St Louis, Missouri, USA
g Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
h School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia
i The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
j Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, California, USA
k Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA
l Dementia Research Centre, University College London (UCL) Institute of Neurology, London, United Kingdom
m Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
n Department of Neurology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
o German Center for Neurodegenerative Diseases, Munich, Germany
p Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany
q German Center for Neurodegenerative Diseases, Tübingen, Germany
r Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
s Department of Neurology, Columbia University Medical Centre, New York, New York, USA
t Neuroscience Research Australia, Sydney, New South Wales, Australia
u School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia


Abstract
Introduction: The objective of this study was to evaluate the relationship between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers. Methods: In 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self-reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ42, and CSF tau levels was evaluated using linear regression. Results: No differences in brain amyloid load, CSF Aβ42, or CSF tau were observed between low and high exercise groups. Nevertheless, when examining only those already accumulating AD pathology (i.e., amyloid positive), low exercisers had higher mean levels of brain amyloid than high exercisers. Furthermore, the interaction between exercise and estimated years from expected symptom onset was a significant predictor of brain amyloid levels. Discussion: Our findings indicate a relationship exists between self-reported exercise levels and brain amyloid in autosomal dominant AD mutation carriers. © 2017 the Alzheimer's Association.


Author Keywords
Alzheimer's disease;  Amyloid β;  Dementia;  Genetics;  Physical activity;  Tau


Document Type: Article in Press
Source: Scopus

 

15) 

Pan, Y.a , Smithson, L.J.a , Ma, Y.a , Hambardzumyan, D.b , Gutmann, D.H.a 
Ccl5 establishes an autocrine high-grade glioma growth regulatory circuit critical for mesenchymal glioblastoma survival
(2017) Oncotarget, 8 (20), pp. 32977-32989. 

DOI: 10.18632/oncotarget.16516


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Oncology, Aflac Cancer and Blood Disorders Center, Emory UniversityGA, United States


Abstract
Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a median survival of 15 months. These poor clinical outcomes have prompted the development of drugs that block neoplastic cancer cell growth; however, non-neoplastic cell-derived signals (chemokines and cytokines) in the tumor microenvironment may also represent viable treatment targets. One such chemokine, Ccl5, produced by lowgrade tumor-associated microglia, is responsible for maintaining neurofibromatosis type 1 (NF1) mouse optic glioma growth in vivo. Since malignant gliomas may achieve partial independence from growth regulatory factors produced by non-neoplastic cells in the tumor microenvironment by producing the same cytokines secreted by the stromal cells in their low-grade counterparts, we tested the hypothesis that CCL5/CCL5-receptor signaling in glioblastoma creates an autocrine circuit important for high-grade glioma growth. Herein, we demonstrate that increased CCL5 expression was restricted to both human and mouse mesenchymal GBM (M-GBM), a molecular subtype characterized by NF1 loss. We further show that the NF1 protein, neurofibromin, negatively regulates Ccl5 expression through suppression of AKT/ mTOR signaling. Consistent with its role as a glioblastoma growth regulator, Ccl5 knockdown in M-GBM cells reduces M-GBM cell survival in vitro, and increases mouse glioblastoma survival in vivo. Finally, we demonstrate that Ccl5 operates through an unconventional CCL5 receptor, CD44, to inhibit M-GBM apoptosis. Collectively, these findings reveal an NF1-dependent CCL5-mediated pathway that regulates M-GBM cell survival, and support the concept that paracrine factors important for low-grade glioma growth can be usurped by high-grade tumors to create autocrine regulatory circuits that maintain malignant glioma survival. © Pan et al.


Author Keywords
CD44;  Chemokine;  Glioma;  MTOR;  Neurofibromin


Document Type: Article
Source: Scopus

 

16) 

Cain, M.D.a , Salimi, H.a , Gong, Y.a , Yang, L.a , Hamilton, S.L.a , Heffernan, J.R.a , Hou, J.a , Miller, M.J.a , Klein, R.S.a b c 
Virus entry and replication in the brain precedes blood-brain barrier disruption during intranasal alphavirus infection
(2016) Journal of Neuroimmunology, . Article in Press. 

DOI: 10.1016/j.jneuroim.2017.04.008


a Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, United States
c Department of Neuroscience, Washington University School of Medicine, St Louis, MO 63110, United States


Abstract
Viral infections of the central nervous system (CNS) are often associated with blood-brain barrier (BBB) disruption, yet the impact of virus replication and immune cell recruitment on BBB integrity are incompletely understood. Using two-photon microscopy, we demonstrate that Venezuelan equine encephalitis virus (VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation within the 5' UTR that is associated with increased sensitivity to type I interferons (IFNs), does not directly impact BBB permeability. Following intranasal infection of both wild-type and IFN-induced protein with tetratricopeptide repeats 1 (IFIT1)-deficient mice, which fail to block TC83-specific RNA translation, virus spreads to the olfactory bulb and cortex via migration along axonal tracts of neurons originating from the olfactory neuroepithelium. Global dissemination of virus in the CNS by 2days post-infection (dpi) was associated with increased BBB permeability in the olfactory bulb, but not in the cortex or hindbrain, where permeability only increased after the recruitment of CX3CR1+ and CCR2+ mononuclear cells on 6 dpi, which corresponded with tight junction loss and claudin 5 redistribution. Importantly, despite higher levels of viral replication, similar results were obtained in IFIT1-deficient mice. These findings indicate that TC83 gains CNS access via anterograde axonal migration without directly altering BBB function and that mononuclear and endothelial cell interactions may underlie BBB disruption during alphavirus encephalitis. © 2017.


Document Type: Article in Press
Source: Scopus

May 22, 2017

1) 

Müller, S.a , Preische, O.a b , Sohrabi, H.R.c d , Gräber, S.b e , Jucker, M.b f , Dietzsch, J.e , Ringman, J.M.g , Martins, R.N.c d , McDade, E.h , Schofield, P.R.i j , Ghetti, B.k , Rossor, M.l , Graff-Radford, N.R.m n , Levin, J.o p , Galasko, D.q , Quaid, K.A.r , Salloway, S.s , Xiong, C.t , Benzinger, T.u , Buckles, V.u , Masters, C.L.v , Sperling, R.w, Bateman, R.J.u , Morris, J.C.u , Laske, C.b e 
Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer's disease
(2017) Scientific Reports, 7 (1), art. no. 1225, . 

DOI: 10.1038/s41598-017-01327-w


a Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
b German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
c Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Perth, WA, Australia
d School of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, WA, Australia
e Section for Dementia Research, Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
f Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
g Memory and Aging Center, Keck School of Medicine of USC, Los Angeles, CA, United States
h University of Pittsburgh School of Medicine, Department of Neurology, 3471 5th Ave, Suite 811, Pittsburgh, PA, United States
i Neuroscience Research Australia, Randwick, Sydney, NSW, Australia
j School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
k Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, United States
l Dementia Research Centre, Department of Neurodegeneration, UCL Institute of Neurology, Queen Square, London, United Kingdom
m Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
n Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
o German Center for Neurodegenerative Diseases (DZNE), München, Germany
p Department of Neurology, Ludwig-Maximilians Universität Munich, Munich, Germany
q Shiley-Marcos Alzheimer's Disease Research Center, Department of Neurosciences, University of California, San Diego, CA, United States
r Indiana University Center for Bioethics, 410 West 10th Street, Indianapolis, IN, United States
s Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, United States
t Division of Biostatistics, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, United States
u Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. LouisMO, United States
v Mental Health Research Institute, University of Melbourne, Level 5, Kenneth Myer Building, 30 Royal Parade, Parkville, VIC, Australia
w Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States


Abstract
The relationship between body-mass index (BMI) and Alzheimers disease (AD) has been extensively investigated. However, BMI alterations in preclinical individuals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before expected symptom onset. However, the BMI curves begun to diverge already at 17.8 years before expected symptom onset. Lower BMI in preclinical MCs was significantly associated with less years before estimated symptom onset, higher global Aβ brain burden, and with lower delayed total recall scores in the logical memory test. The study provides cross-sectional evidence that weight loss starts one to two decades before expected symptom onset of ADAD. Our findings point toward a link between the pathophysiology of ADAD and disturbance of weight control mechanisms. Longitudinal follow-up studies are warranted to investigate BMI changes over time. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

2) 

Schindler, S.E.a b c , Jasielec, M.S.d , Weng, H.d , Hassenstab, J.J.a b , Grober, E.e , McCue, L.M.d , Morris, J.C.a b, Holtzman, D.M.a b c , Xiong, C.a b d , Fagan, A.M.a b c 
Neuropsychological measures that detect early impairment and decline in preclinical Alzheimer disease
(2017) Neurobiology of Aging, 56, pp. 25-32. 

DOI: 10.1016/j.neurobiolaging.2017.04.004


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
d Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Albert Einstein College of Medicine, New York, NY, United States


Abstract
Identifying which neuropsychological measures detect early cognitive changes associated with Alzheimer disease (AD), brain pathology would be helpful clinically for the diagnosis of early AD and for the design of clinical trials. We evaluated which neuropsychological measures in our cognitive battery are most strongly associated with cerebrospinal fluid (CSF) biomarkers of AD brain pathology. We studied a large cohort (n = 233) of middle-to older-aged community-dwelling individuals (mean age 61 years) who had no clinical symptoms of dementia and underwent baseline CSF collection at baseline. Participants completed a battery of 9 neuropsychological measures at baseline and then every 1 to 3 years. CSF tau/Aβ42 was associated with baseline performance on 5/9 neuropsychological measures, especially measures of episodic memory, and longitudinal performance on 7/9 neuropsychological measures, especially measures of global cognition. The free recall portion of the Free and Cued Selective Reminding Task (FCSRT-free) detected declining cognition in the high CSF tau/Aβ42 group the earliest, followed by another measure of episodic memory and a sequencing task. © 2017 Elsevier Inc.


Author Keywords
Cerebrospinal fluid;  Neuropsychological measures;  Preclinical Alzheimer disease;  Subtle cognitive decline


Document Type: Article
Source: Scopus

 

3) 

Oh, S.-H.a , Choi, Y.-B.b , Kim, J.-H.b , Weihl, C.C.c , Ju, J.-S.a 
Quantification of autophagy flux using LC3 ELISA
(2017) Analytical Biochemistry, 530, pp. 57-67. 

DOI: 10.1016/j.ab.2017.05.003


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


Abstract
Macroautophagy (hereafter referred to as autophagy) is a degradation system that delivers cytoplasmic materials to lysosomes via autophagosomes. Autophagic flux is defined as a measure of autophagic degradation activity. Despite several methods for monitoring autophagic flux being currently utilized, interest in finding a highly accurate, sensitive and well-quantifiable assay is still growing. Therefore, we introduce a new approach analyzing autophagic flux in vitro and in vivo using enzyme-linked immunosorbent assay (ELISA) technique. In order to adapt this assay from LC3-II turnover measured by Western blot in the presence and absence of lysosomal inhibitors, we induced autophagy by starvation or rapamycin and mitophagy (mitochondrial degradation by autophagy) by CCCP in C2C12 myotubes for 8 h and in mice for 48 h with and without Bafilomycin A1 or colchicine treatment, respectively. Following subcellular fractionation of mouse skeletal muscle cells and tissue, cytosolic, membrane, and mitochondrial fractions were analyzed through a sandwich ELISA using two LC3 antibodies, LC3 capture and HRP-conjugated LC3 detection antibodies. Using this ELISA, changes in the membrane-bound or mitochondrion-associated LC3-II levels, and the ratio of the LC3-II from each fraction to LC3-I levels (cytosolic fraction) were evaluated for measuring autophagy and mitophagy flux. This study demonstrates that this ELISA was more sensitive and reliable to measure autophagic/mitophagic flux in both in vitro and in vivo, compared with the most commonly used LC3 turnover assay via Western blot. © 2017 Elsevier Inc.


Author Keywords
Autophagy;  ELISA;  LC3 turnover;  Mitophagy;  Skeletal muscle


Document Type: Article
Source: Scopus

 

4) 

Du, F.a b , Wang, X.a c , Abrams, R.A.d , Zhang, K.a b 
Emotional processing is enhanced in peri-hand space
(2017) Cognition, 165, pp. 39-44. 

DOI: 10.1016/j.cognition.2017.04.009


a CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
b University of Chinese Academy of Sciences, Beijing, China
c School of Psychology, Jiangxi Normal University, Nanchang, Jiangxi, China
d Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States


Abstract
The space near the hands, or peri-hand space is a critical multisensory-motor interface between people and the environment. Recent studies have shown that visual processing near the hands is altered compared with stimuli far from the hands. Some results suggest that the changes may be mediated by brain mechanisms involved in evaluating emotional stimuli. Here we show direct evidence for that proposal: we found that both the emotional Stroop effect and the Late Positive Potential (LPP) to unpleasant visual stimuli were enhanced near the hands compared to far from the hands. The results reveal enhanced processing of unpleasant stimuli in peri-hand space, which may facilitate the response to potentially dangerous stimuli. © 2017 Elsevier B.V.


Author Keywords
Emotional Stroop;  Event-related potentials;  Hand-stimulus proximity;  Late positive potential;  Peri-hand space


Document Type: Article
Source: Scopus

 

5) 

Davis, S.A.a , Gan, K.A.a , Dowell, J.A.b , Cairns, N.J.c , Gitcho, M.A.a 
TDP-43 expression influences amyloidβ plaque deposition and tau aggregation
(2017) Neurobiology of Disease, 103, pp. 154-162. 

DOI: 10.1016/j.nbd.2017.04.012


a Department of Biological Sciences, Delaware Center for Neuroscience Research, Delaware State University, Dover, DE, United States
b Wisconsin Institute of Discovery, Madison, WI, United States
c Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Although the main focus in Alzheimer's disease (AD) has been an investigation of mechanisms causing Aβ plaque deposition and tau tangle formation, recent studies have shown that phosphorylated TDP-43 pathology is present in up to 50% of sporadic cases. Furthermore, elevated phosphorylated TDP-43 has been associated with more severe AD pathology. Therefore, we hypothesized that TDP-43 may regulate amyloid-beta precursor protein (APP) trafficking and tau phosphorylation/aggregation. In order to examine the role of TDP-43 in AD, we developed a transgenic mouse that overexpresses hippocampal and cortical neuronal TDP-43 in a mouse expressing familial mutations (K595N and M596L) in APP and presenilin 1 (PSEN1ΔE9). In our model, increased TDP-43 was related to increased tau aggregation as evidenced by thioflavin S-positive phosphorylated tau, which may implicate TDP-43 expression in pre-tangle formation. In addition, there was increased endosomal/lysosomal localization of APP and reduced Aβ plaque formation with increased TDP-43. Furthermore, there was decreased calcineurin with elevated TDP-43 expression. Since calcineurin is a phosphatase for TDP-43, the decreased calcineurin expression may be one mechanism leading to an increase in accumulation of diffuse phosphorylated TDP-43 in the hippocampus and cortex. We further show that when TDP-43 is knocked down there is an increase in calcineurin. In our model of selective TDP-43 overexpression in an APP/PSEN1 background, we show that TDP-43 decreases Aβ plaque deposition while increasing abnormal tau aggregation. These observations indicate that TDP-43 may play a role in regulating APP trafficking and tau aggregation. Our data suggest that TDP-43 could be a putative target for therapeutic intervention in AD affecting both Aβ plaque formation and tauopathy. © 2017 Elsevier Inc.


Author Keywords
Alzheimer's disease;  APP;  APP/PS1;  Calcineurin;  TARDBP;  Tau;  TDP-43


Document Type: Article
Source: Scopus

 

6) 

Gruber, J.a , Van Meter, A.b , Gilbert, K.E.c , Youngstrom, E.A.d , Youngstrom, J.K.d , Feeny, N.C.e , Findling, R.L.f 
Positive Emotion Specificity and Mood Symptoms in an Adolescent Outpatient Sample
(2017) Cognitive Therapy and Research, 41 (3), pp. 393-405. 

DOI: 10.1007/s10608-016-9796-7


a Department of Psychology and Neuroscience, University of Colorado Boulder, 1905 Colorado Avenue, 345 UCB, Muenzinger D321C, Boulder, CO, United States
b Ferkauf Graduate School, Yeshiva University, New York, NY, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
e Case Western Reserve University, Cleveland, OH, United States
f Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States


Abstract
Research on positive emotion disturbance has gained increasing attention, yet it is not clear which specific positive emotions are affected by mood symptoms, particularly during the critical period of adolescence. This is especially pertinent for identifying potential endophenotypic markers associated with mood disorder onset and course. The present study examined self-reported discrete positive and negative emotions in association with clinician-rated manic and depressive mood symptoms in a clinically and demographically diverse group of 401 outpatient adolescents between 11 and 18 years of age. Results indicated that higher self reported joy and contempt were associated with increased symptoms of mania, after controlling for symptoms of depression. Low levels of joy and high sadness uniquely predicted symptoms of depression, after controlling for symptoms of mania. Results were independent of age, ethnicity, gender and bipolar diagnosis. These findings extend work on specific emotions implicated in mood pathology in adulthood, and provide insights into associations between emotions associated with goal driven behavior with manic and depressive mood symptom severity in adolescence. In particular, joy was the only emotion associated with both depressive and manic symptoms across adolescent psychopathology, highlighting the importance of understanding positive emotion disturbance during adolescent development. © 2016, Springer Science+Business Media New York.


Author Keywords
Adolescence;  Depression;  Mania;  Positive emotion


Document Type: Article
Source: Scopus

 

7) 

Meacham, K.a b , Shepherd, A.a b , Mohapatra, D.P.a b , Haroutounian, S.a b 
Neuropathic Pain: Central vs. Peripheral Mechanisms
(2017) Current Pain and Headache Reports, 21 (6), art. no. 28, . 

DOI: 10.1007/s11916-017-0629-5


a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Purpose of Review: Our goal is to examine the processes—both central and peripheral—that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent evidence for mechanisms contributing to its maintenance. While many pNP conditions are initiated by damage to the peripheral nervous system (PNS), their persistence appears to rely on maladaptive processes within the central nervous system (CNS). The potential existence of an autonomous pain-generating mechanism in the CNS creates significant implications for the development of new neuropathic pain treatments; thus, work towards its resolution is crucial. Here, we seek to identify evidence for PNS and CNS independently generating neuropathic pain signals. Recent Findings: Recent preclinical studies in pNP support and provide key details concerning the role of multiple mechanisms leading to fiber hyperexcitability and sustained electrical discharge to the CNS. In studies regarding central mechanisms, new preclinical evidence includes the mapping of novel inhibitory circuitry and identification of the molecular basis of microglia-neuron crosstalk. Recent clinical evidence demonstrates the essential role of peripheral mechanisms, mostly via studies that block the initially damaged peripheral circuitry. Clinical central mechanism studies use imaging to identify potentially self-sustaining infra-slow CNS oscillatory activity that may be unique to pNP patients. Summary: While new preclinical evidence supports and expands upon the key role of central mechanisms in neuropathic pain, clinical evidence for an autonomous central mechanism remains relatively limited. Recent findings from both preclinical and clinical studies recapitulate the critical contribution of peripheral input to maintenance of neuropathic pain. Further clinical investigations on the possibility of standalone central contributions to pNP may be assisted by a reconsideration of the agreed terms or criteria for diagnosing the presence of central sensitization in humans. © 2017, Springer Science+Business Media New York.


Author Keywords
Central sensitization;  Chronic pain;  Hyperexcitability;  Neuropathic pain;  Neuroplasticity;  Painful neuropathy;  Peripheral nerve damage


Document Type: Review
Source: Scopus

 

8) 

Ke, Q.a , Zhao, Z.-Y.b , Griggs, R.c , Wiley, V.d , Connolly, A.e , Kwon, J.f , Qi, M.g , Sheehan, D.h , Ciafaloni, E.i , Howell, R.R.j , Furu, P.k , Sazani, P.l , Narayana, A.m , Gatheridge, M.n 
Newborn screening for Duchenne muscular dystrophy in China: Follow-up diagnosis and subsequent treatment
(2017) World Journal of Pediatrics, pp. 1-5. Article in Press. 

DOI: 10.1007/s12519-017-0036-3


a Department of Neurology, Zhejiang University School of Medicine, Hangzhou, China
b Department of Child Health Care, Zhejiang University School of Medicine, Hangzhou, China
c Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
d Disciplines of Genetic Medicine and Pediatric and Child Health, University of Sydney, Sydney, Australia
e Departments of Neurology and Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
f Departments of Neurology and Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
g Center for Genetic & Genomic Medicine, Zhejiang University School of Medicine and James Watson Institute of Genome Sciences, Hangzhou, China
h Department of Pediatrics, University of Buffalo, Buffalo, NY, United States
i Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
j University of Miami, Business Manager Neonatal Screening, PerkinElmer, Turku, Finland
k Senior Direction, Field Medical Affairs, Marathon Pharmaceuticals, Northbrook, IL, United States
l Sr. Medical Director, Sarepta Therapeutics, Cambridge, MA, United States
m Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
n Department of Neurology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 673, Rochester, NY, United States


Abstract
Background: Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province, China and is under consideration in other countries, including the United States. As China begins to implement DMD newborn screening (DMDNBS), there is ongoing discussion regarding the steps forward for follow up care of positively identifi ed patients as well as false positive and false negative results. Data sources: Relevant papers related to DMD-NBS, and NBS in China were reviewed in PubMed. Results: The current state of DMD-NBS is discussed, along with the steps needed to effectively screen infants for this disease in China, recommendations for establishment of follow up care in patients with positive and negative screens, and measurement of patient outcomes. Conclusions: Zhejiang Province, China is ready to implement DMD-NBS. Future challenges that exist for this program, and other countries, include the ability to track patients, assist with access to care, and ensure adequate follow-up care according to evidence-based guidelines. In addition, China's large rural population, lack of specialty providers, and difficulty in educating patients regarding the benefi ts of treatment create challenges that will need to be addressed. © 2017 Children's Hospital, Zhejiang University School of Medicine and Springer-Verlag Berlin Heidelberg


Author Keywords
Duchene muscular dystrophy;  neurology;  neuromuscular disorders;  newborn screening


Document Type: Article in Press
Source: Scopus

 

9) 

Yang, C.a , Gonzalez-Perez, V.a , Mukaibo, T.b c , Melvin, J.E.b , Xia, X.-M.a , Lingle, C.J.a 
Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (18), pp. E3739-E3747. 

DOI: 10.1073/pnas.1703081114


a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Secretory Mechanisms and Dysfunction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
c Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Fukuoka, Japan


Abstract
Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca2+- and voltage-dependent BK-type K+ channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca2+, suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KOmicewith a β-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons. We establish the presence of LRRC26 protein in eight secretory tissues or tissues with significant secretory epithelium and show that LRRC26 protein coassembles with the pore-forming BK α-subunit in at least three tissues: lacrimal gland, parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar cells, LRRC26 KO shifts BK gating to be like α-subunit-only BK channels. Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K+] in saliva. LRRC26-containing BK channels are competent to contribute to resting K+ efflux at normal cell membrane potentials with resting cytosolic Ca2+ concentrations and likely play a critical physiological role in supporting normal secretory function in all secretory epithelial cells.


Author Keywords
BK channels;  LRRC26;  Salivary glands;  Secretory epithelium;  SLO1


Document Type: Article
Source: Scopus

 

10) 

Smolkina, M.a , Morley, K.I.a b , Rijsdijk, F.c , Agrawal, A.d , Bergin, J.E.e , Nelson, E.C.d , Statham, D.f , Martin, N.G.g , Lynskey, M.T.a 
Cannabis and Depression: A Twin Model Approach to Co-morbidity
(2017) Behavior Genetics, pp. 1-11. Article in Press. 

DOI: 10.1007/s10519-017-9848-0


a National Addiction Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, Addiction Sciences Building, 4 Windsor Walk, SE5 8BB, London, United Kingdom
b Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
c Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United Kingdom
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
e Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States
f Faculty of Arts, Business and Law, School of Social Sciences, University of the Sunshine Coast, Sippy Downs, QLD, Australia
g Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia


Abstract
Cannabis use disorder (CUD) co-occurs with major depressive disorder (MDD) more frequently than would be expected by chance. However, studies to date have not produced a clear understanding of the mechanisms underlying this co-morbidity. Genetically informative studies can add valuable insight to this problem, as they allow the evaluation of competing models of co-morbidity. This study uses data from the Australian Twin Registry to compare 13 co-morbidity twin models initially proposed by Neale and Kendler (Am J Hum Genet 57:935–953, 1995). The analysis sample comprised 2410 male and female monozygotic and dizygotic twins (average age 32) who were assessed on CUD and MDD using the SSAGA-OZ interview. Data were analyzed in OpenMx. Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD. Both fit substantially better than the Correlated Liabilities model. Although the current study cannot differentiate between them statistically, these models, in combination, suggest that CUD risk factors may causally influence the risk to develop MDD, but only when risk for CUD is high. © 2017 The Author(s)


Author Keywords
Cannabis use disorder;  Co-morbidity;  Genetics;  Major depressive disorder;  Twin model


Document Type: Article in Press
Source: Scopus

 

11) 

Saa, J.P.a b , Doherty, M.a , Young, A.a , Spiers, M.c , Leary, E.d , Wolf, T.J.c 
Development and alternate form reliability of the Complex Task Performance Assessment (CTPA) for people with mild stroke
(2017) American Journal of Occupational Therapy, 71 (3), art. no. 024356, . 

DOI: 10.5014/ajot.2017.024356


a Program in Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States
b George Warren Brown School of Social Work and Public Health, Washington University, St. Louis, MO, United States
c Department of Occupational Therapy, University of Missouri, Columbia, United States
d Biostatistics and Research Design Unit, University of Missouri, Columbia, United States


Abstract
Cognitive impairment is a common consequence of mild stroke. Current performance-based assessments for mild stroke can detect mild impairments in executive function but lack alternate forms to be used as outcome measures. This study aimed to develop an alternate form of the Complex Task Performance Assessment (CTPA-Alt), a performance-based assessment of executive function, and to establish the alternate form reliability of the CTPA-Alt. A repeated-measures study was conducted with 26 community participants. Participants were screened for eligibility and administered both forms of the CTPA; administration order was alternated. Overall performance was significantly correlated (rs =.44, p =.03), but pattern of scoring differed by CTPA form and order of administration. Our results indicate that the CTPA forms were similar but that the specific tasks in each form were different. The CTPA may be used as an ecologically valid outcome assessment with further considerations.


Document Type: Article
Source: Scopus

 

12) 

Shaw, J.A.a , Bryant, L.K.b , Malle, B.F.c , Povinelli, D.J.d , Pruett, J.R., Jr.e 
The relationship between joint attention and theory of mind in neurotypical adults
(2017) Consciousness and Cognition, 51, pp. 268-278. 

DOI: 10.1016/j.concog.2017.02.012


a Medical Scientist Training Program, Philosophy-Neuroscience-Psychology Program, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO, United States
b Vanderbilt Brain Institute, Vanderbilt University School of Medicine, 2215 Garland Ave., Nashville, TN, United States
c Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, 190 Thayer Street, Providence, RI, United States
d Department of Biology, University of Louisiana, 104 University Circle, Lafayette, LA, United States
e Department of Psychiatry, Washington University in St. Louis, School of Medicine, 660 S. Euclid Ave., St. Louis, MO, United States


Abstract
Joint attention (JA) is hypothesized to have a close relationship with developing theory of mind (ToM) capabilities. We tested the co-occurrence of ToM and JA in social interactions between adults with no reported history of psychiatric illness or neurodevelopmental disorders. Participants engaged in an experimental task that encouraged nonverbal communication, including JA, and also ToM activity. We adapted an in-lab variant of experience sampling methods (Bryant et al., 2013) to measure ToM during JA based on participants’ subjective reports of their thoughts while performing the task. This experiment successfully elicited instances of JA in 17/20 dyads. We compared participants’ thought contents during episodes of JA and non-JA. Our results suggest that, in adults, JA and ToM may occur independently. © 2017 The Authors


Author Keywords
Experience sampling;  Joint attention;  Social cognition;  Theory of mind


Document Type: Article
Source: Scopus

 

13) 

Krauss, M.J., Grucza, R.A., Bierut, L.J., Cavazos-Rehg, P.A.
"get drunk. Smoke weed. Have fun.": A Content Analysis of Tweets about Marijuana and Alcohol
(2017) American Journal of Health Promotion, 31 (3), pp. 200-208. 

DOI: 10.4278/ajhp.150205-QUAL-708


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


Abstract
Purpose. To explore the sentiment and themes of Twitter chatter that mentions both alcohol and marijuana. Design. Cross-sectional analysis of tweets mentioning both alcohol and marijuana during 1 month was performed. Setting. The study setting was Twitter. Participants. Tweets sent from February 4 to March 5, 2014, were studied. Method. A random sample (n = 5000) of tweets that mentioned alcohol and marijuana were qualitatively coded as normalizing both substances, preferring one substance over the other, or discouraging both substances. Other common themes were identified. Results. More than half (54%) of the tweets normalized marijuana and alcohol (without preferring one substance over the other), and 24% preferred marijuana over alcohol. Only 2% expressed a preference for alcohol over marijuana, 7% discouraged the use of both substances, and the sentiment was unknown for 13% of the tweets. Common themes among tweets that normalized both substances included using the substances with friends (17%) and mentioning substance use in the context of sex or romance (14%). Common themes among tweets that preferred marijuana over alcohol were the beliefs that marijuana is safer than alcohol (46%) and preferences for effects of marijuana over alcohol (40%). Conclusion. Tweets normalizing polysubstance use or encouraging marijuana use over alcohol use are common. Both online and offline prevention efforts are needed to increase awareness of the risks associated with polysubstance use and marijuana use. © 2016 by American Journal of Health Promotion, Inc.


Author Keywords
Health focus: social health;  Outcome measure: behavioral;  Research purpose: descriptive;  Setting: national;  Social Media, Alcohol, Marijuana, Twitter, Prevention Research. Manuscript format: research;  Strategy: behavior change;  Study design: content analysis;  Target population age: youth, adults;  Target population circumstances: education/income level


Document Type: Article
Source: Scopus

 

14) 

Colonna, M.a , Butovsky, O.b 
Microglia function in the central nervous system during health and neurodegeneration
(2017) Annual Review of Immunology, 35, pp. 441-468. 

DOI: 10.1146/annurev-immunol-051116-052358


a Department of Pathology and Immunology, Washington University, School of Medicine, St. Louis, MO, United States
b Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States


Abstract
Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration. Recent observations about microglia ontogeny combined with extensive gene expression profiling and novel tools to study microglia biology have allowed us to characterize the spectrum of microglial phenotypes during development, homeostasis, and disease. In this article, we review recent advances in our understanding of the biology of microglia, their contribution to homeostasis, and their involvement in neurodegeneration. Moreover, we highlight the complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases. © 2017 by Annual Reviews. All rights reserved.


Author Keywords
Homeostasis;  Microglia;  Neurodegeneration;  Phenotypes;  Receptors;  Regulation


Document Type: Review
Source: Scopus

 

15) 

Walter, C.a , Crawford, L.b , Lai, M.c , Toonen, J.A.b , Pan, Y.b , Sakiyama-Elbert, S.d , Gutmann, D.H.b , Pathak, A.a c 
Increased Tissue Stiffness in Tumors from Mice with Neurofibromatosis-1 Optic Glioma
(2017) Biophysical Journal, 112 (8), pp. 1535-1538. 

DOI: 10.1016/j.bpj.2017.03.017


a Department of Biomedical Engineering, Washington University, St. Louis, Missouri, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States
c Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, Missouri, United States
d Department of Biomedical Engineering, University of Texas-Austin, Austin, Texas, United States


Abstract
Children with neurofibromatosis type 1 (NF1) cancer predisposition syndrome are prone to the development of low-grade brain tumors (gliomas) within the optic pathway (optic gliomas). One of the key obstacles to developing successful therapeutic strategies for these tumors is the striking lack of information about the mechanical properties that characterize these tumors relative to non-neoplastic optic nerve tissue. To study the physical changes that may occur when an optic nerve glioma is present, we employed atomic force microscopy to measure the stiffness of healthy versus tumor-bearing optic nerve tissue. We found that the average elastic moduli of non-neoplastic and tumor-bearing optic nerves were 3 and 6 kPa, respectively. Based on previous studies implicating changes in extracellular matrix remodeling in other, related optic nerve pathological states, we found decreased expression of one major metalloproteinase protein (MMP-2) and unchanged expression of lysyl oxidase and a second metalloproteinase, MMP-9, in murine optic gliomas relative to normal non-neoplastic optic nerve. Collectively, these observations suggest a productive interplay between physical properties of mouse optic nerve gliomas and the extracellular matrix. © 2017 Biophysical Society


Document Type: Article
Source: Scopus

 

16) 

Wong, A.W.K.a b , Ng, S.b c , Dashner, J.a , Baum, M.C.d , Hammel, J.e , Magasi, S.f , Lai, J.-S.g , Carlozzi, N.E.h, Tulsky, D.S.i , Miskovic, A.j , Goldsmith, A.j , Heinemann, A.W.j k 
Relationships between environmental factors and participation in adults with traumatic brain injury, stroke, and spinal cord injury: a cross-sectional multi-center study
(2017) Quality of Life Research, pp. 1-13. Article in Press. 

DOI: 10.1007/s11136-017-1586-5


a Program in Occupational Therapy and Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Program in Occupational Therapy, Washington University School of Medicine, 4444 Forest Park Ave, Campus Box 8505, St. Louis, MO, United States
c Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
d Program in Occupational Therapy, Department of Neurology and George Warren Brown School of Social Work, Washington University, St. Louis, MO, United States
e Departments of Occupational Therapy and Disability and Human Development, University of Illinois at Chicago, Chicago, IL, United States
f Department of Occupational Therapy, University of Illinois at Chicago, Chicago, IL, United States
g Departments of Medical Social Science and Pediatric, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
h Department of Physical Medicine and Rehabilitation, University of Michigan Medical School, Ann Arbor, MI, United States
i Department of Physical Therapy, University of Delaware, Newark, DE, United States
j Center for Rehabilitation Outcomes Research, Rehabilitation Institute of Chicago, Chicago, IL, United States
k Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, United States


Abstract
Purpose: To develop and evaluate a model of environmental factors-participation relationships for persons with traumatic brain injury (TBI), stroke, and spinal cord injury (SCI), and test whether this model differed across three diagnostic groups, as well as other demographic and clinical characteristics. Methods: A cross-sectional observational study included 545 community-dwelling adults with neurological disorders (TBI = 166; stroke = 189; SCI = 190) recruited at three academic medical centers. Participants completed patient-reported measures of environmental factors and participation. Results: The final structural equation model had acceptable fit to the data (CFI = 0.923; TLI = 0.898; RMSEA = 0.085; SRMR = 0.053), explaining 63% of the variance in participation in social roles and activities. Systems, services, and policies had an indirect influence on participation and this relation was mediated by social attitudes and the built and natural environment. Access to information and technology was associated with the built and natural environment which in turn influence on participation (ps < 0.001). The model was consistent across sex, diagnosis, severity/type of injury, education, race, age, marital status, years since injury, wheelchairs use, insurance coverage, personal or household income, and crystallized cognition. Conclusions: Social and physical environments appear to mediate the influence of systems, services, and policies on participation after acquired neurological disorders. These relations are stable across three diagnostic groups and many personal and clinical factors. Our findings inform health and disability policy, and provide guidance for implementing the initiatives in Healthy People 2020 in particular for people with acquired neurological disorders. © 2017 Springer International Publishing Switzerland


Author Keywords
Environment;  Participation;  Spinal cord injury;  Stroke;  Traumatic brain injury


Document Type: Article in Press
Source: Scopus

 

17) 

McCarty, S., Eickmeyer, S.M., Kocherginsky, M., Keeshin, S., Shahpar, S., Semik, P., Wong, A.W.K.
Health-Related Quality of Life and Cancer-Related Symptoms During Interdisciplinary Outpatient Rehabilitation for Malignant Brain Tumor
(2017) American Journal of Physical Medicine and Rehabilitation, . Article in Press. 

DOI: 10.1097/PHM.0000000000000756


From the Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, Illinois (SM, SK, SS); Physical Medicine and Rehabilitation, University of Kansas Medical Center, Kansas City, Kansas (SME); Department of Preventive Medicine, Division of Biostatistics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (MK); Center of Rehabilitation Outcomes Research, Rehabilitation Institute of Chicago, Chicago, Illinois (PS); and Occupational Therapy and Neurology, Washington University School of Medicine, St. Louis, Missouri (AWKW).


Abstract
OBJECTIVE: The aim of the study was to determine the relationships between functional outcomes, clinical symptoms, and health-related quality of life among patients with malignant brain tumors receiving interdisciplinary outpatient rehabilitation. DESIGN: A prospective study of 49 adults with malignant brain tumors participating in outpatient therapies was performed. Outcome measures included the Functional Assessment of Cancer Therapy-Brain (FACT-Br) for health-related quality of life and the Patient-Reported Outcome Measures Instrument Survey (PROMIS) Depression and Pain Behavior scales measured at admission, discharge, 1 and 3 mos after discharge. Day Rehabilitation Outcome Scale, a functional measure, was measured at admission and discharge. RESULTS: The FACT-Br scores, PROMIS pain, and PROMIS depression scores did not significantly change. There were many negative associations seen between FACT-Br and PROMIS depression (all P < .0001) and less associations with PROMIS pain. There was a positive correlation between Day Rehabilitation Outcome Scale and FACT-Br (P = .0058) and a negative association with PROMIS pain (P = .028), but not with PROMIS depression. There were no correlations between Day Rehabilitation Outcome Scale gains and change in PROMIS depression, FACT-Br total, or PROMIS pain. CONCLUSIONS: Health-related quality of life, pain, and depression did not worsen. Patients who reported less depression and pain had better reported health-related quality of life. Level of function was also associated with HRQOL and pain, but not depression. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Document Type: Article in Press
Source: Scopus

 

18) 

Bauernfeind, A.L.a b , Babbitt, C.C.c 
The predictive nature of transcript expression levels on protein expression in adult human brain
(2017) BMC Genomics, 18 (1), art. no. 322, . 

DOI: 10.1186/s12864-017-3674-x


a Washington University Medical School, Department of Neuroscience, St. Louis, MO, United States
b Washington University in St. Louis, Department of Anthropology, St. Louis, MO, United States
c University of Massachusetts Amherst, Department of Biology, Amherst, MA, United States


Abstract
Background: Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Results: Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R2 values of &lt; 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. Conclusions: The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples. © 2017 The Author(s).


Author Keywords
Chimpanzee;  Gene;  Proteomics;  RNA-Seq


Document Type: Article
Source: Scopus

 

19) 

Ulrich, J.D.a b c , Ulland, T.K.d , Colonna, M.d , Holtzman, D.M.a b c 
Elucidating the Role of TREM2 in Alzheimer's Disease
(2017) Neuron, 94 (2), pp. 237-248. 

DOI: 10.1016/j.neuron.2017.02.042


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
c Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Alzheimer's disease (AD) is the sixth leading cause of death in the United States and the most common cause of dementia in the elderly. Genetic factors, such as rare variants in the microglial-expressed gene TREM2, strongly impact the lifetime risk of developing AD. Several recent studies have described dramatic TREM2-dependent phenotypes in mouse models of amyloidosis that point to an important role for TREM2 in regulating the response of the innate immune system to Aβ pathology. Furthermore, elevations in the CSF levels of soluble TREM2 fragments implicate changes in inflammatory pathways as occurring coincident with markers of neuronal damage and the onset of clinical dementia in AD. Here, we review the rapidly developing literature surrounding TREM2 in AD that may provide novel insight into the broader role of the innate immune system in neurodegenerative disease. © 2017 Elsevier Inc.


Author Keywords
Alzheimer's disease;  microglia;  TREM2


Document Type: Review
Source: Scopus

 

20) 

Yanamandra, K.a b , Patel, T.K.a , Jiang, H.a , Schindler, S.a , Ulrich, J.D.a , Boxer, A.L.c , Miller, B.L.c , Kerwin, D.R.d , Gallardo, G.a , Stewart, F.a , Finn, M.B.a , Cairns, N.J.a , Verghese, P.B.e , Fogelman, I.e , West, T.e , Braunstein, J.e , Robinson, G.a , Keyser, J.a , Roh, J.a , Knapik, S.S.e , Hu, Y.e , Holtzman, D.M.a 
Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy
(2017) Science Translational Medicine, 9 (386), art. no. eaal2029, . 

DOI: 10.1126/scitranslmed.aal2029


a Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University, St. Louis, MO, United States
b AbbVie Inc., Foundational Neuroscience Center, Cambridge, MA, United States
c Clinical Trials Program, Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
d Texas Alzheimer's and Memory Disorders, Texas Health Presbyterian Hospital Dallas, Dallas, TX, United States
e C2N Diagnostics, Center for Emerging Technologies, 4041 Forest Park Avenue, St. Louis, MO, United States


Abstract
Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. 2017 © The Authors.


Document Type: Article
Source: Scopus

 

21) 

Mahdi, J.a , Shah, A.C.c , Sato, A.d , Morris, S.M.a , McKinstry, R.C.b , Listernick, R.e , Packer, R.J.d , Fisher, M.J.c f , Gutmann, D.H.a 
A multi-institutional study of brainstem gliomas in children with neurofibromatosis type 1
(2017) Neurology, 88 (16), pp. 1584-1589. 

DOI: 10.1212/WNL.0000000000003881


a Departments of Neurology, United States
b Departments of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
c Division of Oncology, Children's Hospital of PhiladelphiaPA, United States
d Center for Neuroscience of Behavioral Medicine, Children's National Medical Center, Washington, DC, United States
e Division of Academic General Pediatrics, Feinberg School of Medicine, Northwestern University, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States
f Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States


Abstract
Objective: To define the clinical and radiologic features of brainstem gliomas (BSGs) in children with neurofibromatosis type 1 (NF1). Methods: We performed a retrospective cross-sectional study of 133 children with NF1 and concurrent BSGs cared for at 4 NF1 referral centers. BSG was determined using radiographic criteria. Age at diagnosis, tumor location and appearance, clinical symptoms, treatment, and presence of a concurrent optic pathway glioma were assessed. Results: The average age at BSG diagnosis was 7.2 years, and tumors occurred most often in the midbrain and medulla (66%). The majority of children with NF1-BSGs were asymptomatic (54%) and were not treated (88%). Only 9 of the 72 asymptomatic children received treatment because of progressive tumor enlargement. In contrast, 61 children presented with clinical signs/symptoms attributable to their BSG; these individuals were older and more often had focal lesions. Thirty-one patients underwent treatment for their tumor, and 14 received CSF diversion only. Progression-free survival was 3 years shorter for children receiving tumor-directed therapy relative to those who had either no treatment or CSF diversion only. Overall survival was 85% for the tumor-directed therapy group, whereas no deaths were reported in the untreated or CSF diversion groups. Conclusions: Unlike children with sporadically occurring BSGs, most children with NF1-BSGs were asymptomatic, and few individuals died from complications of their tumor. Those requiring tumor-directed treatment tended to be older children with focal lesions, and had clinically more aggressive disease relative to those who were not treated or underwent CSF diversion only. © 2017 American Academy of Neurology.


Document Type: Article
Source: Scopus

 

22) 

Marrie, R.A.a , Salter, A.b , Tyry, T.c , Cutter, G.R.d , Cofield, S.d , Fox, R.J.e 
High hypothetical interest in physician-assisted death in multiple sclerosis
(2017) Neurology, 88 (16), pp. 1528-1534. Cited 1 time.

DOI: 10.1212/WNL.0000000000003831


a Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
b Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States
c Dignity Health, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States
d Department of Biostatistics, University of Alabama at Birmingham, United States
e Mellen Center, Department of Neurology, Cleveland ClinicOH, United States


Abstract
Objective: To assess the opinions of persons with multiple sclerosis (MS) regarding physician-assisted death (PAD). Methods: We surveyed participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding PAD. For each of 5 hypothetical situations, respondents indicated whether they definitely would, probably would, probably would not, or definitely would not consider PAD. They also reported their sociodemographics, disability status using Patient-Determined Disease Steps, depression status, pain status, religiosity, and degree of social support. Using multivariable logistic regression models, we evaluated the factors associated with an individual reporting that he or she would definitely or probably consider PAD in each situation. Results: Of 7,534 respondents, 6,011 (79.8%) were female, and 6,884 (92.9%) were white. Their mean (SD) age was 59.9 (10.2) years. Fifty percent of respondents reported at least moderate disability. Of the 6,792 respondents who responded to any of the PAD questions, 6,400 responded to all questions. Of these, 458 (7.1%) indicated that they would definitely consider PAD in all of the situations listed, while 1,275 (19.9%) indicated that they definitely would not consider PAD in any of the situations listed. If experiencing unbearable pain, 4,383 (65.3%) of respondents would definitely or probably consider PAD. On multivariable analysis, religiosity, social support, depression, pain, disability, sex, and race were associated with considering PAD in some or all of the situations presented. Conclusions: Depending upon the situation, a large proportion of persons with MS would consider PAD. The association of depression with considering PAD emphasizes the importance of diagnosing and treating depression. © 2017 American Academy of Neurology.


Document Type: Article
Source: Scopus

 

23) 

Ghossoub, E.a , Ghandour, L.A.b , Halabi, F.c , Zeinoun, P.d , Shehab, A.A.S.e , Maalouf, F.T.a 
Prevalence and correlates of ADHD among adolescents in a Beirut community sample: Results from the BEI-PSY Study
(2017) Child and Adolescent Psychiatry and Mental Health, 11 (1), art. no. 20, . 

DOI: 10.1186/s13034-017-0156-5


a American University of Beirut, Department of Psychiatry, P.O. Box 11-0236, Riad El-Solh/Beirut, Lebanon
b American University of Beirut, Department of Epidemiology and Population Health, Faculty of Health Sciences, Beirut, Lebanon
c Washington University in St. Louis, Department of Psychiatry, St. Louis, United States
d Faculty of Arts and Sciences, American University of Beirut, Department of Psychology, Beirut, Lebanon
e Queens College, City University of New York, Department of PsychologyNY, United States


Abstract
Background: This study aims to investigate the prevalence, correlates and treatment seeking behavior related to ADHD among adolescents from Lebanon. Methods: Five hundred and ten adolescents were recruited through multistage stratified cluster sampling of households in Beirut, and separately interviewed along with one parent/legal guardian, using the DAWBA. All adolescents completed the PRQ and the SDQ; the parent/legal guardian also completed the SDQ and provided basic demographic information, including attitudes towards seeking mental health services. Results: 10.20% of the adolescents were diagnosed with ADHD. Having ADHD was associated with having academic difficulties and being involved in bullying. Adolescents with ADHD also had higher odds of drinking alcohol, smoking cigarettes, and having comorbid emotional and conduct disorders (compared to those without ADHD). Adolescents with ADHD and their parents reported a higher burden of illness and were more likely to consider seeing a mental health professional than healthy adolescents and their parents. Conclusion: ADHD among adolescents in Lebanon warrants closer attention, mainly increased awareness in the larger public, and stronger commitment to increase treatment resources to the community. © 2017 The Author(s).


Author Keywords
Attention deficit disorder with hyperactivity;  Epidemiology;  Lebanon;  Patient acceptance of health care


Document Type: Article
Source: Scopus

 

24) 

Liu, C.-C.a , Hu, J.a c , Zhao, N.a , Wang, J.a , Wang, N.a c , Cirrito, J.R.b , Kanekiyo, T.a , Holtzman, D.M.b , Bu, G.a c 
Astrocytic LRP1 mediates brain Aβ clearance and impacts amyloid deposition
(2017) Journal of Neuroscience, 37 (15), pp. 4023-4031. 

DOI: 10.1523/JNEUROSCI.3442-16.2017


a Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
b Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
c Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian, China


Abstract
Accumulation and deposition of amyloid-β (Aβ) in the brain represent an early and perhaps necessary step in the pathogenesis of Alzheimer’s disease (AD). Aβ accumulation leads to the formation of Aβ aggregates, which may directly and indirectly lead to eventual neurodegeneration. While Aβ production is accelerated in many familial forms of early-onset AD, increasing evidence indicates that impaired clearance of Aβ is more evident in late-onset AD. To uncover the mechanisms underlying impaired Aβ clearance in AD, we examined the role of low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Although LRP1 has been shown to play critical roles in brain Aβ metabolism in neurons and vascular mural cells, its role in astrocytes, the most abundant cell type in the brain responsible for maintaining neuronal homeostasis, remains unclear. Here, we show that astrocytic LRP1 plays a critical role in brain Aβ clearance. LRP1 knockdown in primary astrocytes resulted in decreased cellular Aβ uptake and degradation. In addition, silencing of LRP1 in astrocytes led to downregulation of several majorAβ-degrading enzymes, including matrix metalloproteasesMMP2,MMP9,and insulin-degrading enzyme. More important, conditional knock-out of the Lrp1 gene in astrocytes in the background of APP/PS1 mice impaired brainAβ clearance, exacerbatedAβ accumulation, and accelerated amyloid plaque deposition without affecting its production. Together, our results demonstrate that astrocyticLRP1plays an important role inAβ metabolism and that restoringLRP1expression and function in the brain could be an effective strategy to facilitate Aβ clearance and counter amyloid pathology in AD. © 2017 the authors.


Author Keywords
Alzheimer’s disease;  Amyloid-β;  LRP1


Document Type: Article
Source: Scopus

 

25) 

Shahim, P.a b c , Tegner, Y.d , Marklund, N.e , Höglund, K.a b c , Portelius, E.a b c , Brody, D.L.f g h , Blennow, K.a , Zetterberg, H.a b c i 
Astroglial activation and altered amyloid metabolism in human repetitive concussion
(2017) Neurology, 88 (15), pp. 1400-1407. 

DOI: 10.1212/WNL.0000000000003816


a Institute of Neuroscience and Physiology, United States
b Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Sweden
c Clinical Neurochemistry Laboratory, Sweden
d Sahlgrenska University Hospital, Division of Medical Sciences, Department of Health Sciences, Sweden
e Luleå University of Technology, Department of Neuroscience, Neurosurgery, Sweden
f Uppsala University, Uppsala, Sweden
g Washington University, School of Medicine, St. Louis, MO, United States
h Department of Molecular Neuroscience, United States
i UCL Institute of Neurology, London, United Kingdom


Abstract
Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment. Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio). Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS >1 year. Athletes with PCS >1 year had higher RPQ scores and number of concussions than athletes with PCS <1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS >1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of Aβ40 and Aβ42 than controls. The CSF:serum albumin ratio was unaltered. Conclusions: This study suggests that PCS may be associated with biomarker evidence of astroglial activation and β-amyloid (Aβ) dysmetabolism in the brain. There was no clear evidence of Aβ deposition as Aβ40 and Aβ42 were reduced in parallel. The CSF:serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS. © 2017 American Academy of Neurology.


Document Type: Article
Source: Scopus

 

26) 

Guerriero, R.M., Schlaggar, B.L.
An important step toward a functional biomarker in pediatric TBI recovery and outcome
(2017) Neurology, 88 (15), pp. 1386-1387. 

DOI: 10.1212/WNL.0000000000003822


From the Department of Neurology, Division of Pediatric and Developmental Neurology, Washington University, St. Louis, MO, United States


Document Type: Editorial
Source: Scopus

 

27) 

Takeda, A.a , Perlmutter, J.S.b 
Striatal molecular imaging of presynaptic markers
(2017) Neurology, 88 (15), pp. 1388-1389. 

DOI: 10.1212/WNL.0000000000003827


a Department of Neurology, National Hospital Organization, Sendai-Nishitaga Hospital, Sendai, Miyagi, Japan
b Departments of Neurology, Radiology, Washington University, School of Medicine, St. Louis, MO, United States


Document Type: Editorial
Source: Scopus

 

28) 

Lin, T.-H.a , Chiang, C.-W.a g , Perez-Torres, C.J.a h , Sun, P.a , Wallendorf, M.b , Schmidt, R.E.c , Cross, A.H.d e , Song, S.-K.a e f i 
Diffusion MRI quantifies early axonal loss in the presence of nerve swelling
(2017) Journal of Neuroinflammation, 14 (1), art. no. 78, . 

DOI: 10.1186/s12974-017-0852-3


a Washington University School of Medicine, Radiology, 660 S Euclid Ave, St. Louis, MO, United States
b Washington University School of Medicine, Biostatistics, 660 S Euclid Ave, St. Louis, MO, United States
c Washington University School of Medicine, Pathology, 660 S Euclid Ave, St. Louis, MO, United States
d Washington University School of Medicine, Neurology, 660 S Euclid Ave, St. Louis, MO, United States
e Washington University School of Medicine, Hope Center for Neurological Disorders, 660 S Euclid Ave, St. Louis, MO, United States
f Washington University, Biomedical Engineering, 1 Brookings Dr, St. Louis, MO, United States
g National Health Research Institute, Institute of Biomedical Engineering and Nanomedicine, 35 Keyan Road, Zhunan, Miaoli County, Taiwan
h Purdue University, School of Health Sciences, 550 W Stadium Ave, West Lafayette, IN, United States
i Washington University School of Medicine, Biomedical MR Laboratory, Campus Box 8227, 4525 Scott Ave, St Louis, MO, United States


Abstract
Background: Magnetic resonance imaging markers have been widely used to detect and quantify white matter pathologies in multiple sclerosis. We have recently developed a diffusion basis spectrum imaging (DBSI) to distinguish and quantify co-existing axonal injury, demyelination, and inflammation in multiple sclerosis patients and animal models. It could serve as a longitudinal marker for axonal loss, a primary cause of permanent neurological impairments and disease progression. Methods: Eight 10-week-old female C57BL/6 mice underwent optic nerve DBSI, followed by a week-long recuperation prior to active immunization for experimental autoimmune encephalomyelitis (EAE). Visual acuity of all mice was assessed daily. Longitudinal DBSI was performed in mouse optic nerves at baseline (naïve, before immunization), before, during, and after the onset of optic neuritis. Tissues were perfusion fixed after final in vivo scans. The correlation between DBSI detected pathologies and corresponding immunohistochemistry markers was quantitatively assessed. Results: In this cohort of EAE mice, monocular vision impairment occurred in all animals. In vivo DBSI detected, differentiated, and quantified optic nerve inflammation, demyelination, and axonal injury/loss, correlating nerve pathologies with visual acuity at different time points of acute optic neuritis. DBSI quantified, in the presence of optic nerve swelling, ~15% axonal loss at the onset of optic neuritis in EAE mice. Conclusions: Our findings support the notion that axonal loss could occur early in EAE mice. DBSI detected pathologies in the posterior visual pathway unreachable by optical coherence tomography and without confounding inflammation induced optic nerve swelling. DBSI could thus decipher the interrelationship among various pathological components and the role each plays in disease progression. Quantification of the rate of axonal loss could potentially serve as the biomarker to predict treatment outcome and to determine when progressive disease starts. © 2017 The Author(s).


Author Keywords
Axonal loss;  DBSI;  Diffusion MRI;  Multiple sclerosis;  Optic neuritis


Document Type: Article
Source: Scopus

 

29) 

Smith, S.B.a , Lichtenhan, J.T.b , Cone, B.K.a 
Contralateral inhibition of click- and chirp-evoked human compound action potentials
(2017) Frontiers in Neuroscience, 11 (APR), art. no. 189, . 

DOI: 10.3389/fnins.2017.00189


a Department of Speech, Language and Hearing Sciences, University of Arizona, Tucson, AZ, United States
b Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Cochlear outer hair cells (OHC) receive direct efferent feedback from the caudal auditory brainstem via the medial olivocochlear (MOC) bundle. This circuit provides the neural substrate for the MOC reflex, which inhibits cochlear amplifier gain and is believed to play a role in listening in noise and protection from acoustic overexposure. The human MOC reflex has been studied extensively using otoacoustic emissions (OAE) paradigms; however, these measurements are insensitive to subsequent "downstream" efferent effects on the neural ensembles that mediate hearing. In this experiment, click- and chirp-evoked auditory nerve compound action potential (CAP) amplitudes were measured electrocochleographically from the human eardrum without and with MOC reflex activation elicited by contralateral broadband noise. We hypothesized that the chirp would be a more optimal stimulus for measuring neural MOC effects because it synchronizes excitation along the entire length of the basilar membrane and thus evokes a more robust CAP than a click at low to moderate stimulus levels. Chirps produced larger CAPs than clicks at all stimulus intensities (50-80 dB ppeSPL). MOC reflex inhibition of CAPs was larger for chirps than clicks at low stimulus levels when quantified both in terms of amplitude reduction and effective attenuation. Effective attenuation was larger for chirp- and click-evoked CAPs than for click-evoked OAEs measured from the same subjects. Our results suggest that the chirp is an optimal stimulus for evoking CAPs at low stimulus intensities and for assessing MOC reflex effects on the auditory nerve. Further, our work supports previous findings that MOC reflex effects at the level of the auditory nerve are underestimated by measures of OAE inhibition. © 2017 Smith, Lichtenhan and Cone.


Author Keywords
Chirps;  Compound action potential;  Efferent auditory system;  Electrocochleography;  Medial olivocochlear reflex


Document Type: Article
Source: Scopus

 

30) 

Frontera, W.R.a b , Bean, J.F.c d , Damiano, D.e , Ehrlich-Jones, L.f , Fried-Oken, M.g , Jette, A.h , Jung, R.i , Lieber, R.L.f , Malec, J.F.j , Mueller, M.J.k , Ottenbacher, K.J.l , Tansey, K.E.m , Thompson, A.n 
Rehabilitation Research at the National Institutes of Health
(2017) Neurorehabilitation and Neural Repair, 31 (4), pp. 304-314. 

DOI: 10.1177/1545968317698875


a Department of Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 2201 Children's Way, Nashville, TN, United States
b Department of Physical Medicine, Rehabilitation, and Sports Medicine, University of Puerto Rico, School of Medicine, San Juan, Puerto Rico, Puerto Rico
c Harvard Medical School, Boston, MA, United States
d New England GRECC, VA Boston Healthcare SystemMA, United States
e National Institutes of Health, Bethesda, MD, United States
f Northwestern Feinberg Medical School and Rehabilitation Institute of ChicagoIL, United States
g Oregon Health and Science University, Portland, OR, United States
h Boston UniversityMA, United States
i Florida International University, Miami, FL, United States
j Indiana University, School of Medicine and Rehabilitation, Hospital of Indiana, Indianapolis, IN, United States
k Washington University, School of Medicine, St Louis, MO, United States
l University of Texas Medical Branch, Galveston, TX, United States
m Jackson Veteran's Administration Medical CenterMS, United States
n Medical University of South Carolina, Charleston, SC, United States


Document Type: Article
Source: Scopus

 

31) 

Hawasli, A.H.a , Chacko, R.b , Szrama, N.P.b , Bundy, D.T.b , Pahwa, M.b , Yarbrough, C.K.a , Dlouhy, B.J.c , Limbrick, D.D.a , Barbour, D.L.b , Smyth, M.D.a , Leuthardt, E.C.a b 
Electrophysiological sequelae of hemispherotomy in ipsilateral human cortex
(2017) Frontiers in Human Neuroscience, 11, art. no. 149, . 

DOI: 10.3389/fnhum.2017.00149


a Department of Neurological Surgery, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO, United States
c Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States


Abstract
Objectives: Hemispheric disconnection has been used as a treatment of medically refractory epilepsy and evolved from anatomic hemispherectomy to functional hemispherectomies to hemispherotomies. The hemispherotomy procedure involves disconnection of an entire hemisphere with limited tissue resection and is reserved for medically-refractory epilepsy due to diffuse hemispheric disease. Although it is thought to be effective by preventing seizures from spreading to the contralateral hemisphere, the electrophysiological effects of a hemispherotomy on the ipsilateral hemisphere remain poorly defined. The objective of this study was to evaluate the effects of hemispherotomy on the electrophysiologic dynamics in peri-stroke and dysplastic cortex. Methods: Intraoperative electrocorticography (ECoG) was recorded from ipsilateral cortex in 5 human subjects with refractory epilepsy before and after hemispherotomy. Power spectral density, mutual information, and phase-amplitude coupling were measured from the ECoG signals. Results: Epilepsy was a result of remote perinatal stroke in three of the subjects. In two of the subjects, seizures were a consequence of dysplastic tissue: one with hemimegalencephaly and the second with Rasmussen's encephalitis. Hemispherotomy reduced broad-band power spectral density in peri-stroke cortex. Meanwhile, hemispherotomy increased power in the low and high frequency bands for dysplastic cortex. Functional connectivity was increased in lower frequency bands in peri-stroke tissue but not affected in dysplastic tissue after hemispherotomy. Finally, hemispherotomy reduced band-specific phase-amplitude coupling in peristroke cortex but not dysplastic cortex. Significance: Disconnecting deep subcortical connections to peri-stroke cortex via a hemispherotomy attenuates power of oscillations and impairs the transfer of information from large-scale distributed brain networks to the local cortex. Hence, hemispherotomy reduces heterogeneity between neighboring cortex while impairing phase-amplitude coupling. In contrast, dysfunctional networks in dysplastic cortex lack the normal connectivity with distant networks. Therefore hemispherotomy does not produce the same effects. © 2017 Hawasli, Chacko, Szrama, Bundy, Pahwa, Yarbrough, Dlouhy, Limbrick, Barbour, Smyth and Leuthardt.


Author Keywords
Cortical physiology;  Electrocorticography;  Epilepsy;  Hemispherotomy;  Oscillations


Document Type: Article
Source: Scopus

 

32) 

Wang, S.a b , Peterson, D.J.b , Wang, Y.c d e , Wang, Q.d , Grabowski, T.J.b f , Li, W.a , Madhyastha, T.M.b 
Empirical comparison of diffusion kurtosis imaging and diffusion basis spectrum imaging using the same acquisition in healthy young adults
(2017) Frontiers in Neurology, 8 (MAR), art. no. 118, . 

DOI: 10.3389/fneur.2017.00118


a Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
b Department of Radiology, University of Washington, Seattle, WA, United States
c Department of Obstetrics and Gynecology, Washington University, St. Louis, MO, United States
d Department of Radiology, Washington University, St. Louis, MO, United States
e Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
f Department of Neurology, University of Washington, Seattle, WA, United States


Abstract
As diffusion tensor imaging gains widespread use, many researchers have been motivated to go beyond the tensor model and fit more complex diffusion models, to gain a more complete description of white matter microstructure and associated pathology. Two such models are diffusion kurtosis imaging (DKI) and diffusion basis spectrum imaging (DBSI). It is not clear which DKI parameters are most closely related to DBSI parameters,so in the interest of enabling comparisons between DKI and DBSI studies, we conducted an empirical survey of the interrelation of these models in 12 healthy volunteers using the same diffusion acquisition. We found that mean kurtosis is positively associated with the DBSI fiber ratio and negatively associated with the hindered ratio. This was primarily driven by the radial component of kurtosis. The axial component of kurtosis was strongly and specifically correlated with the restricted ratio. The joint spatial distributions of DBSI and DKI parameters are tissue-dependent and stable across healthy individuals. Our contribution is a better understanding of the biological interpretability of the parameters generated by the two models in healthy individuals. © 2017 Wang, Peterson, Wang, Wang, Grabowski, Li and Madhyastha.


Author Keywords
Diffusion basis spectrum imaging;  Diffusion kurtosis imaging;  Diffusion magnetic resonance imaging;  Diffusion tensor imaging;  Model comparison


Document Type: Article
Source: Scopus

 

33) 

Soundararajan, S.a , Narayanan, G.b , Agrawal, A.c , Murthy, P.b 
Personality profile and short-term treatment outcome in patients with alcohol dependence: A study from South India
(2017) Indian Journal of Psychological Medicine, 39 (2), pp. 169-175. 

DOI: 10.4103/0253-7176.203127


a Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
b Department of Psychiatry, Centre for Addiction Medicine, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
c Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States


Abstract
Background: Studying personality profiles allows researchers to generate important hypotheses in risk factors and correlates of alcohol use/misuse. Studies examining the association between personality traits and treatment outcome are limited in India. We studied the correlation between personality and treatment outcome in patients with alcohol dependence. Methods: Adult participants with alcohol dependence were recruited from the inpatient and outpatient wards of de-addiction unit of a tertiary care facility in India using a prospective design and followed up after 3 months. Questionnaires administered were revised NEO personality inventory (NEO-PI-R), alcohol use disorders identification test, and advanced warning of alcohol relapse (AWARE). Results: Out of 99 recruited participants (92% males) with mean age of 37 (±8.36) years, 82 (82.8%) patients were followed up to 3 months. E4 (activity) facet of the extraversion domain in the NEO-PI-R significantly correlated with the baseline drinking scores (r = 0.204, P = 0.042, n = 99) and AWARE scores (r = 0.276, P = 0.043, n = 54). There was a significant negative correlation between the E2 (gregariousness) facet and satisfaction with life scores (r = -0.211, P = 0.036, n = 99). Age at first drink was significantly lower among relapsers (P = 0.021). Conclusion: Our study suggests that factors related to extraversion, specifically, high activity might be associated with higher drinking as well as higher risk of alcohol relapse. Predicting alcohol relapse by studying the personality traits would help clinicians in improving treatment outcomes. © 2017 Indian Psychiatric Society.


Author Keywords
Alcohol dependence;  extraversion;  personality;  relapse;  revised NEO personality inventory


Document Type: Article
Source: Scopus

 

34) 

Kober, D.L.a b , Brett, T.J.b c d 
TREM2-Ligand Interactions in Health and Disease
(2017) Journal of Molecular Biology, . Article in Press. 

DOI: 10.1016/j.jmb.2017.04.004


a Molecular Microbiology and Microbial Pathogenesis Program, Washington University School of Medicine, St. Louis, MO 63110, USA
b Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
c Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA
d Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA


Abstract
The protein triggering receptor expressed on myeloid cells-2 (TREM2) is an immunomodulatory receptor with a central role in myeloid cell activation and survival. In recent years, the importance of TREM2 has been highlighted by the identification of coding variants that increase risk for Alzheimer's disease and other neurodegenerative diseases. Animal studies have further shown the importance of TREM2 in neurodegenerative and other inflammatory disease models including chronic obstructive pulmonary disease, multiple sclerosis, and stroke. A mechanistic understanding of TREM2 function remains elusive, however, due in part to the absence of conclusive information regarding the identity of endogenous TREM2 ligands. While many TREM2 ligands have been proposed, their physiological role and mechanism of engagement remain to be determined. In this review, we highlight the suggested roles of TREM2 in these diseases and the recent advances in our understanding of TREM2 and discuss putative TREM2-ligand interactions and their potential roles in signaling during health and disease. We develop a model based on the TREM2 structure to explain how different TREM2 ligands might interact with the receptor and how disease risk variants may alter ligand interactions. Finally, we propose future experimental directions to establish the role and importance of these different interactions on TREM2 function. © 2017 Elsevier Ltd.


Author Keywords
Alzheimer's disease;  Immune signaling;  Inflammation;  Microglia;  Neurodegeneration


Document Type: Article in Press
Source: Scopus

 

35) 

Salas, J.a b , Scherrer, J.F.a b c , Schneider, F.D.a , Sullivan, M.D.d , Bucholz, K.K.e , Burroughs, T.c , Copeland, L.A.f g h , Ahmedani, B.K.i , Lustman, P.J.e j 
New-onset depression following stable, slow, and rapid rate of prescription opioid dose escalation
(2017) Pain, 158 (2), pp. 306-312. 

DOI: 10.1097/j.pain.0000000000000763


a Department of Family and Community Medicine, Saint Louis University School of Medicine, 1402 S. Grand Blvd, St Louis, MO, United States
b Harry S. Truman Veterans Administration Medical Center, Columbia, MO, United States
c Saint Louis University Center for Outcomes Research, St. Louis, MO, United States
d Department of Psychiatry and Behavioral Health, University of Washington School of Medicine, Seattle, WA, United States
e Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
f Center for Applied Health Research, Baylor Scott and White Health, Central Texas Veterans Health Care System, Temple, TX, United States
g Texas AandM Health Science Center, Bryan, TX, United States
h UT Health Science Center, San Antonio, TX, United States
i Henry Ford Health System, Center for Health Policy and Health Services Research and Behavioral Health Services DetroitMI, United States
j Bell Street Clinic, VA St. Louis Health Care System-John Cochran Division, St. Louis, MO, United States


Abstract
Recent studies suggest that longer durations of opioid use, independent of maximum morphine equivalent dose (MED) achieved, is associated with increased risk of new-onset depression (NOD). Conversely, other studies, not accounting for duration, found that higher MED increased probability of depressive symptoms. To determine whether rate of MED increase is associated with NOD, a retrospective cohort analysis of Veterans Health Administration data (2000-2012) was conducted. Eligible patients were new, chronic (>90 days) opioid users, aged 18 to 80, and without depression diagnoses for 2 years before start of follow-up (n = 7051). Mixed regression models of MED across follow-up defined 4 rate of dose change categories: Stable, decrease, slow increase, and rapid increase. Cox proportional hazard models assessed the relationship of rate of dose change and NOD, controlling for pain, duration of use, maximum MED, and other confounders using inverse probability of treatment-weighted propensity scores. Incidence rate for NOD was 14.1/1000PY (person-years) in stable rate, 13.0/1000PY in decreasing, 19.3/1000PY in slow increasing, and 27.5/1000PY in rapid increasing dose. Compared with stable rate, risk of NOD increased incrementally for slow (hazard ratio = 1.22; 95% confidence interval: 1.05-1.42) and rapid (hazard ratio = 1.58; 95% confidence interval: 1.30-1.93) rate of dose increase. Faster rates of MED escalation contribute to NOD, independent of maximum dose, pain, and total opioid duration. Dose escalation may be a proxy for loss of control or undetected abuse known to be associated with depression. Clinicians should avoid rapid dose increase when possible and discuss risk of depression with patients if dose increase is warranted for pain. © 2016 International Association for the Study of Pain.


Author Keywords
Depression;  Epidemiology;  Opioids;  Retrospective cohort


Document Type: Article
Source: Scopus

 

36) 

Jung, M.E.a , Colletta, M.a , Coalson, R.b , Schlaggar, B.L.c , Lieu, J.E.C.a 
Differences in interregional brain connectivity in children with unilateral hearing loss
(2017) Laryngoscope, . Article in Press. 

DOI: 10.1002/lary.26587


a Department of Otolaryngology-Head and Neck SurgeryWashington University School of MedicineSt. Louis, Missouri U.S.A
b Departments of Neurology and RadiologyWashington University School of MedicineSt. Louis, Missouri U.S.A
c Departments of NeurologyRadiology, Neuroscience, Psychiatry, and Pediatrics, Washington University School of MedicineSt. Louis, Missouri U.S.A


Abstract
Objectives: To identify functional network architecture differences in the brains of children with unilateral hearing loss (UHL) using resting-state functional-connectivity magnetic resonance imaging (rs-fcMRI). Study Design: Prospective observational study. Methods: Children (7 to 17 years of age) with severe to profound hearing loss in one ear, along with their normal hearing (NH) siblings, were recruited and imaged using rs-fcMRI. Eleven children had right UHL; nine had left UHL; and 13 had normal hearing. Forty-one brain regions of interest culled from established brain networks such as the default mode (DMN); cingulo-opercular (CON); and frontoparietal networks (FPN); as well as regions for language, phonological, and visual processing, were analyzed using regionwise correlations and conjunction analysis to determine differences in functional connectivity between the UHL and normal hearing children. Results: When compared to the NH group, children with UHL showed increased connectivity patterns between multiple networks, such as between the CON and visual processing centers. However, there were decreased, as well as aberrant connectivity patterns with the coactivation of the DMN and FPN, a relationship that usually is negatively correlated. Conclusion: Children with UHL demonstrate multiple functional connectivity differences between brain networks involved with executive function, cognition, and language comprehension that may represent adaptive as well as maladaptive changes. These findings suggest that possible interventions or habilitation, beyond amplification, might be able to affect some children's requirement for additional help at school. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.


Author Keywords
Children;  MRI;  Unilateral hearing loss


Document Type: Article in Press
Source: Scopus

 

37) 

McPherson, C.a b , Smith, J.R.c 
Analgesia in the premature neonate: Walking the tightrope requires a great team
(2017) Journal of Perinatal and Neonatal Nursing, 31 (2), pp. 99-100. 

DOI: 10.1097/JPN.0000000000000245


a Neonatal ICU, St. Louis Children's Hospital, St. Louis, MO, United States
b Department of Pediatrics, Washington University, School of Medicine, St. Louis, MO, United States
c Clinical Quality, Safety and Practice Excellence, St. Louis Children's HospitalMO, United States


Document Type: Note
Source: Scopus

 

38) 

Merz, Z.C.a , Van Patten, R.a , Mulhauser, K.a , Fucetola, R.b 
Exploratory factor analysis of the reintegration to normal living index in a stroke population
(2017) Topics in Stroke Rehabilitation, 24 (2), pp. 158-162. 

DOI: 10.1080/10749357.2016.1215398


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


Abstract
Background: The reintegration to normal living index (RNLI) is a global assessment of patient quality of life often utilized in stroke populations. Previous studies in various general disability samples have consistently reported a two-factor solution for the RNLI. Despite its common use with stroke patients, the RNLI has not been psychometrically evaluated in an exclusively stroke sample. This study is believed to represent the first factor analysis of the RNLI using a sample comprised exclusively of individuals who have survived cerebral infarct. Objective: The aim of this study is to evaluate the psychometric properties of the RNLI in assessing quality of life of stroke survivors. Methods: We retrospectively examined RNLI scores of 928 adults with strokes of varying severities as part of a multidisciplinary, interinstitutional collaboration across an academic medical center, acute care hospital, and rehabilitation center. We utilized a principal component factor analysis to evaluate the factor structure of the RNLI. Results: Mean RNLI scores ±SD for the sample were 75.26 ± 19.85, ranging between 20 and 100. The Cronbach α was.94. A scree test for factor retention strongly suggested a single factor solution, explaining 64.50% of the total variance. Conclusions: Previous factor analyses on the RNLI utilizing general disability samples commonly report a twofactor solution. Our data support the presence of a single factor solution across the RNLI within a large sample comprised exclusively of stroke survivors. This suggests that the RNLI acts as more of a unitary measure of quality of life within a stroke sample relative to other disabled samples. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Author Keywords
Activities of daily living;  Quality of life;  Rehabilitation;  Stroke


Document Type: Article
Source: Scopus

 

39) 

Taylor, S.R.a , Wang, T.J.b , Granados-Fuentes, D.b , Herzog, E.D.b 
Resynchronization dynamics reveal that the ventral entrains the dorsal suprachiasmatic nucleus
(2017) Journal of Biological Rhythms, 32 (1), pp. 35-47. 

DOI: 10.1177/0748730416680904


a Department of Computer Science, Colby College, 5855 Mayflower Hill, Waterville, ME, United States
b Department of Biology, Washington University, St. Louis, MO, United States


Abstract
Although the suprachiasmatic nucleus (SCN) has long been considered the master circadian clock in mammals, the topology of the connections that synchronize daily rhythms among SCN cells is not well understood. We combined experimental and computational methods to infer the directed interactions that mediate circadian synchrony between regions of the SCN. We analyzed PERIOD2 (PER2) expression from SCN slices during and after treatment with tetrodotoxin, allowing us to map connections as cells resynchronized their daily cycling following blockade and restoration of cell-cell communication. Using automated analyses, we found that cells in the dorsal SCN stabilized their periods slower than those in the ventral SCN. A phaseamplitude computational model of the SCN revealed that, to reproduce the experimental results: (1) the ventral SCN had to be more densely connected than the dorsal SCN and (2) the ventral SCN needed strong connections to the dorsal SCN. Taken together, these results provide direct evidence that the ventral SCN entrains the dorsal SCN in constant conditions. © 2016 The Author(s).


Author Keywords
Circadian;  Computational model;  Entrainment;  Period gene;  SCN;  Vasoactive intestinal polypeptide;  Vasopressin


Document Type: Article
Source: Scopus

 

40) 

Lean, R.E.a , Smyser, C.D.b c d , Rogers, C.E.a e 
Assessment. The Newborn
(2017) Child and Adolescent Psychiatric Clinics of North America, . Article in Press. 

DOI: 10.1016/j.chc.2017.02.002


a Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8504, St Louis, MO 63110, USA
b Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St Louis, MO 63110, USA
c Department of Radiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St Louis, MO 63110, USA
d Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St Louis, MO 63110, USA
e Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8504, St Louis, MO 63110, USA


Abstract
Neonatal neurobehavioral assessment has become a standardized component of clinical care provided to newborn infants, guiding neonatal clinical care and subsequent access to early interventions and services. Links between neonatal assessment and neurosensory and motor impairments in high-risk infants have been relatively well established. In contrast, the extent to which newborn neurobehavioral assessment might also facilitate the early identification of infants susceptible to socioemotional impairments in early childhood is less well documented. This review examines longitudinal links between the neonatal neurobehavioral assessment, temperament, and socioemotional outcomes in early childhood. © 2017 Elsevier Inc.


Author Keywords
Assessment;  Neonate;  Neurobehavioral;  Socioemotional impairment;  Temperament


Document Type: Article in Press
Source: Scopus

 

41) 

Mulkey, S.B.a b , Ramakrishnaiah, R.H.b , McKinstry, R.C.c , Chang, T.a , Mathur, A.M.c , Mayock, D.E.d , Van Meurs, K.P.e , Schaefer, G.B.b , Luo, C.b , Bai, S.b , Juul, S.E.d , Wu, Y.W.f 
Erythropoietin and Brain Magnetic Resonance Imaging Findings in Hypoxic-Ischemic Encephalopathy: Volume of Acute Brain Injury and 1-Year Neurodevelopmental Outcome
(2016) Journal of Pediatrics, . Article in Press. 

DOI: 10.1016/j.jpeds.2017.03.053


a Division of Fetal and Transitional Medicine, Children's National Health System, Washington, DC
b University of Arkansas for Medical Sciences, Little Rock, AR
c Washington University, St. Louis, MO
d University of Washington, Seattle, WA
e Stanford University, Palo Alto, CA
f University of California San Francisco, San Francisco, CA


Abstract
In the Neonatal Erythropoietin and Therapeutic Hypothermia Outcomes study, 9/20 erythropoietin-treated vs 12/24 placebo-treated infants with hypoxic-ischemic encephalopathy had acute brain injury. Among infants with acute brain injury, the injury volume was lower in the erythropoietin than the placebo group (P = .004). Higher injury volume correlated with lower 12-month neurodevelopmental scores. Trial registration: ClinicalTrials.gov: NCT01913340. © 2017 Elsevier Inc.


Author Keywords
Brain volumetrics;  Diffusion weighted imaging;  Neuroprotection;  Newborn


Document Type: Article in Press
Source: Scopus

 

42) 

Strahle, J.a b , Maher, C.O.b 
Are arachnoid cysts and Chiari malformation type i more common in those with postconcussion syndrome?
(2016) Journal of Neurosurgery, 125 (5), pp. 1320-1321. 

DOI: 10.3171/2016.4.JNS16788


a Washington University in St. Louis, St. Louis, MO, United States
b University of Michigan, Ann Arbor, MI, United States


Document Type: Editorial
Source: Scopus

 

43) 

Sylvester, P.T.a , Moran, C.J.b , Derdeyn, C.P.a b , Cross, D.T.b , Dacey, R.G.a , Zipfel, G.J.a , Kim, A.H.a , Uppaluri, R.c , Haughey, B.H.c , Tempelhoff, R.d , Rich, K.M.a , Schneider, J.c , Chole, R.A.c , Chicoine, M.R.a 
Endovascular management of internal carotid artery injuries secondary to endonasal surgery: Case series and review of the literature
(2016) Journal of Neurosurgery, 125 (5), pp. 1256-1276. 

DOI: 10.3171/2015.6.JNS142483


a Department of Neurosurgery, Washington University School of Medicine, Box 8057, 660 S. Euclid Ave., St. Louis, MO, United States
b Division of Neuroradiology, Mallinckrodt Institute, Washington University School of Medicine, St. Louis, MO, United States
c Department of Otolaryngology, United States
d Department of Anesthesia, United States


Abstract
Objective Internal carotid artery (ICA) injury is a rare but severe complication of endonasal surgery. The authors describe their endovascular experience managing ICA injuries after transsphenoidal surgery; they review and summarize the current literature regarding endovascular techniques; and they propose a treatment algorithm based on the available evidence. MethoDs A retrospective review of 576 transsphenoidal pituitary adenoma resections was performed. Cases of ICA injury occurring at our institution and transfers from other hospitals were evaluated. Endovascular treatments for ICA injury reported in the literature were also reviewed and summarized. resUlts Seven cases were identifed from the institutional cohort (mean age 46.3 years, mean follow-up 43.4 months [1-107 months]) that received endovascular treatment for ICA injury. Five injuries occurred at our institution (5 [0.9%] of 576), and 2 injuries occurred at outside hospitals. Three patients underwent ICA sacrifce by coil placement, 2 underwent lesion embolization (coil or stent-assisted coil placement), and 2 underwent endoluminal reconstruction (both with flow diversion devices). Review of the literature identifed 98 cases of ICA injury treated with endovascular methods. Of the 105 total cases, 46 patients underwent ICA sacrifce, 28 underwent lesion embolization, and 31 underwent endoluminal reconstruction. Sacrifce of the ICA proved a durable solution in all cases; however, the rate of persistent neurological complications was relatively high (10 [21.7%] of 46). Lesion embolization was primarily performed by coil embolization without stenting (16 cases) and stent-assisted coiling (9 cases). Both techniques had a relatively high rate of at least some technical complication (6 [37.5%] of 16 and 5 [55.6%] of 9, respectively) and major technical complications (i.e., injury, new neurological defcit, or ICA sacrifce) (5 [31.3%] of 16 and 2 [22.2%] of 9, respectively). Endoluminal reconstruction was performed by covered stent (24 cases) and flow diverter (5 cases) placement. Covered stents showed a reasonably high rate of technical complications (10 [41.7%] of 24); however, 8 of these problems were resolved, leaving a small percentage with major technical complications (2 [8.3%] of 24). Flow diverter placement was also well tolerated, with only 1 minor technical complication. coNclUsioNs Endovascular treatments including vessel sacrifce, coil embolization (with or without stent assistance), and endoluminal reconstruction offer a tailored approach to ICA injury management after endonasal surgery. Vessel sacrifce remains the defnitive treatment for acute, uncontrolled bleeding; however, vessel preservation techniques should be considered carefully in select patients. Multiple factors including vascular anatomy, injury characteristics, and risk of dual antiplatelet therapy should guide best treatment, but more study is needed (particularly with flow diverters) to refne this decision-making process. Ideally, all endovascular treatment options should be available at institutions performing endonasal surgery. © 2016 AANS.


Author Keywords
Decision making;  Endonasal surgery;  Endovascular procedures;  Internal carotid artery;  Pituitary surgery;  Treatment outcomes


Document Type: Article
Source: Scopus

 

 

44) 

Lewis, J.D.a , Evans, A.C.a , Pruett, J.R.b c , Botteron, K.N.b c , McKinstry, R.C.c , Zwaigenbaum, L.d , Estes, A.e, Collins, D.L.a , Kostopoulos, P.a , Gerig, G.g , Dager, S.f , Paterson, S.h , Schultz, R.T.h , Styner, M.i j , Hazlett, H.j, Piven, J.j 
The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder
(2016) Biological Psychiatry, . Article in Press. 

DOI: 10.1016/j.biopsych.2017.03.006


a Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
b Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri
c Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri
d Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
e Department of Speech and Hearing Sciences, University of Washington, Seattle, Washington
f Department of Radiology, University of Washington, Seattle, Washington
g Tandon School of Engineering, New York University, Brooklyn, New York
h Center for Autism Research, University of Pennsylvania, Philadelphia, Pennsylvania
i Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina
j Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, North Carolina


Abstract
Background: Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. Methods: This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Results: Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. Conclusions: These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior. © 2017 Society of Biological Psychiatry.


Author Keywords
Autism;  Connectivity;  Development;  Efficiency;  Infant siblings;  Network analysis


Document Type: Article in Press
Source: Scopus

May 15, 2017

1) 

Tien, N.-W.a b , Soto, F.a , Kerschensteiner, D.a c d e 
Homeostatic Plasticity Shapes Cell-Type-Specific Wiring in the Retina
(2017) Neuron, 94 (3), pp. 656-665.e4. 

DOI: 10.1016/j.neuron.2017.04.016


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
d Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States
e Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Convergent input from different presynaptic partners shapes the responses of postsynaptic neurons. Whether developing postsynaptic neurons establish connections with each presynaptic partner independently or balance inputs to attain specific responses is unclear. Retinal ganglion cells (RGCs) receive convergent input from bipolar cell types with different contrast responses and temporal tuning. Here, using optogenetic activation and pharmacogenetic silencing, we found that type 6 bipolar (B6) cells dominate excitatory input to ONα-RGCs. We generated mice in which B6 cells were selectively removed from developing circuits (B6-DTA). In B6-DTA mice, ONα-RGCs adjusted connectivity with other bipolar cells in a cell-type-specific manner. They recruited new partners, increased synapses with some existing partners, and maintained constant input from others. Patch-clamp recordings revealed that anatomical rewiring precisely preserved contrast and temporal frequency response functions of ONα-RGCs, indicating that homeostatic plasticity shapes cell-type-specific wiring in the developing retina to stabilize visual information sent to the brain. © 2017 Elsevier Inc.


Document Type: Article
Source: Scopus

 

2) 

Kim, B.a , Park, S.b , Bishop-Saucier, J.a , Amorim, C.c 
Community-Based Services and Depression from Person-Environment Fit Perspective: Focusing on Functional Impairments and Living Alone
(2017) Journal of Gerontological Social Work, pp. 1-16. Article in Press. 

DOI: 10.1080/01634372.2017.1310166


a University of New Hampshire, Durham, New Hampshire, USA
b George Warren Brown School of Social Work, Washington University in St. Louis, Missouri, USA
c The Institute of Professional Practice, Inc., Concord, New Hampshire, USA


Abstract
Guided by the Person-Environment Fit perspective, we investigated the extent to which personal and environmental factors influence depression among community-dwelling adults. The data came from the special section about community-based service utilization in the 2012 Health and Retirement Study (N=1,710). Although community-based service was not significantly associated with depression after controlling for covariates, respondents with functional limitations and living alone were less likely to be depressed when using community-based services. This study demonstrates the different associations between community-based services and depression depending on personal needs. It discusses the importance of community-based services for aging-in-place policy, particularly among vulnerable populations. © 2017 Taylor & Francis Group, LLC


Author Keywords
Aging-in-place;  community-based services;  depression;  person environment fit;  vulnerable population


Document Type: Article in Press
Source: Scopus

 

3) 

Licis, A.
Sleep Disorders. Assessment and Treatment in Preschool-Aged Children
(2017) Child and Adolescent Psychiatric Clinics of North America, . Article in Press. 

DOI: 10.1016/j.chc.2017.02.009


Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 South Euclid Avenue, St Louis, MO 63110, USA


Abstract
Sleep issues are common in preschoolers, defined in this article as ages 3 to 5 years. Sleep deprivation can cause behavioral and cognitive issues. Sleep issues seen in the preschool years include insomnia, obstructive sleep apnea, parasomnias, and restless legs syndrome. Sleep issues seem to exacerbate mood and attention disturbances. Conversely, children with psychiatric disorders are likely to have sleep problems. Treatment of sleep issues is important for long-term mental health and optimization of functioning. © 2017.


Author Keywords
Pediatric sleep;  Preschool;  Sleep;  Sleep deprivation;  Sleep disorders


Document Type: Article in Press
Source: Scopus

 

4) 

Ibanez, L.a , Dube, U.a b , Budde, J.a , Black, K.a , Medvedeva, A.a , Davis, A.A.c , Perlmutter, J.S.c , Benitez, B.A.d , Cruchaga, C.a e 
TMEM230 in Parkinson's disease
(2016) Neurobiology of Aging, . Article in Press. 

DOI: 10.1016/j.neurobiolaging.2017.03.014


a Department of Psychiatry, School of Medicine, Washington University in Saint Louis, Saint Louis, MO, USA
b Medical Scientist Training Program, School of Medicine, Washington University in Saint Louis, Saint Louis, MO, USA
c Department of Neurology, School of Medicine, Washington University in St Louis, Saint Louis, MO, USA
d Department of Medicine, School of Medicine, Washington University in Saint Louis, Saint Louis, MO, USA
e Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University in Saint Louis, Saint Louis, MO, USA


Abstract
A study on familial Parkinson disease (PD) described 4 variants in the gene TMEM230 (Chr. 20p13) as the cause of PD. The aim of this study was to test if variants in the TMEM230 gene are associated with PD in 2 independent American European data sets. No variants in the TMEM230 region were found associated with PD, age at onset, or cerebrospinal fluid α-synuclein levels. © 2017 Elsevier Inc.


Author Keywords
GWAS;  Parkinson;  TMEM230;  WES


Document Type: Article in Press
Source: Scopus

 

5) 

Randerath, J.a c d , Valyear, K.F.a e , Philip, B.A.a f , Frey, S.H.a b 
Contributions of the parietal cortex to increased efficiency of planning-based action selection
(2016) Neuropsychologia, . Article in Press. 

DOI: 10.1016/j.neuropsychologia.2017.04.024


a Department of Psychological Sciences, University of Missouri, USA
b Brain Imaging Center, University of Missouri, USA
c Department of Psychology, University of Konstanz, Germany
d Lurija Institute, Kliniken Schmieder, Germany
e School of Psychology, Bangor University, UK
f School of Medicine, Washington University Saint Louis, USA


Abstract
Response selection is foundational to adaptive behavior, and considerable attention has been devoted to investigating this behavior under conditions in which the mapping between stimuli and responses is fixed. Results from prior studies implicate the left supramarginal gyrus (SMg), premotor and prefrontal cortices, as well as the cerebellum in this essential function. Yet, many goal-directed motor behaviors have multiple solutions with flexible mappings between stimuli and responses whose solutions are believed to involve prospective planning. Studies of selection under conditions of flexible mappings also reveal involvement of the left SMg, as well as bilateral premotor, superior parietal cortex (SPL) and pre-supplementary motor (pre-SMA) cortices, along with the cerebellum. This evidence is, however, limited by exclusive reliance on tasks that involve selection in the absence of overt action execution and without complete control of possible confounding effects related to differences in stimulus and response processing demands. Here, we address this limitation through use of a novel fMRI repetition suppression (FMRI-RS) paradigm. In our prime-probe design, participants select and overtly pantomime manual object rotation actions when the relationship between stimuli and responses is either flexible (experimental condition) or fixed (control condition). When trials were repeated in prime-probe pairs of the experimental condition, we detected improvements in performance accompanied by a significant suppression of blood oxygen-level dependent (BOLD) responses in: left SMg extending into and along the length of the intraparietal sulcus (IPS), right IPS, bilateral caudal superior parietal lobule (cSPL), dorsal premotor cortex (dPMC), pre-SMA, and in the lateral cerebellum. Further, region-of-interest analyses revealed interaction effects of fMRI-RS in the experimental versus control condition within left SMg and cerebellum, as well as in bilateral caudal SPL. These efficiency effects cannot be attributed to the repetition of stimulus or response processing, but instead are planning-specific and generally consistent with earlier findings from conventional fMRI investigations. We conclude that repetition-related increases in the efficiency of planning-based selection appears to be associated with parieto-cerebellar networks. © 2017 Elsevier Ltd.


Author Keywords
Action selection;  FMRI repetition suppression


Document Type: Article in Press
Source: Scopus

May 1, 2017

1) 

Kass, A.E.a , Wilfley, D.E.b , Eddy, K.T.c , Boutelle, K.N.d , Zucker, N.e , Peterson, C.B.f , Le Grange, D.g , Celio-Doyle, A.h i , Goldschmidt, A.B.j 
Secretive eating among youth with overweight or obesity
(2017) Appetite, 114, pp. 275-281. 

DOI: 10.1016/j.appet.2017.03.042


a Department of Psychiatry & Behavioral Neuroscience, The University of Chicago, 5841 South Maryland Avenue, MC 1000, Chicago, IL, United States
b Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, Box 8134, St. Louis, MO, United States
c Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, United States
d Department of Pediatrics and Psychiatry, University of California, San Diego, 9500 Gilman Drive, MC 0874, La Jolla, CA, United States
e Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, P.O. Box 3842, Durham, NC, United States
f Department of Psychiatry, University of Minnesota Medical School, F282/2A West, 2450 Riverside Avenue South, Minneapolis, MN, United States
g Department of Psychiatry, University of California, San Francisco, 3333 California Street, Suite 245, San Francisco, CA, United States
h Eating Disorders Center at the Evidence Based Treatment Centers of Seattle, 1200 5th Avenue, Suite 800, Seattle, WA, United States
i Department of Psychology, University of Washington, Guthrie Hall (GTH), 119A 98195-1525, Seattle, WA, United States
j Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Weight Control and Diabetes Research Center/The Miriam Hospital, 196 Richmond Street, Providence, RI, United States


Abstract
Purpose Secretive eating, characterized by eating privately to conceal being seen, may reflect eating- and/or body-related shame, be associated with depression, and correlate with binge eating, which predicts weight gain and eating disorder onset. Increasing understanding of secretive eating in youth may improve weight status and reduce eating disorder risk. This study evaluated the prevalence and correlates of secretive eating in youth with overweight or obesity. Methods Youth (N = 577) presented to five research/clinical institutions. Using a cross-sectional design, secretive eating was evaluated in relation to eating-related and general psychopathology via linear and logistic regression analyses. Results Secretive eating was endorsed by 111 youth, who were, on average, older than youth who denied secretive eating (mean age = 12.07 ± 2.83 versus 10.97 ± 2.31). Controlling for study site and age, youth who endorsed secretive eating had higher eating-related psychopathology and were more likely to endorse loss of control eating and purging than their counterparts who did not endorse secretive eating. Groups did not differ in excessive exercise or behavioral problems. Dietary restraint and purging were elevated among adolescents (≥13y) but not children (<13y) who endorsed secretive eating; depression was elevated among children, but not adolescents, who endorsed secretive eating. Conclusions Secretive eating may portend heightened risk for eating disorders, and correlates of secretive eating may differ across pediatric development. Screening for secretive eating may inform identification of problematic eating behaviors, and understanding factors motivating secretive eating may improve intervention tailoring. © 2017 Elsevier Ltd


Author Keywords
Binge eating;  Eating behavior;  Obesity;  Overweight;  Pediatric;  Psychosocial


Document Type: Conference Paper
Source: Scopus

 

2) 

Krauss, M.J.a , Sowles, S.J.a , Sehi, A.a , Spitznagel, E.L.b , Berg, C.J.c , Bierut, L.J.a , Cavazos-Rehg, P.A.a 
Marijuana advertising exposure among current marijuana users in the U.S.
(2017) Drug and Alcohol Dependence, 174, pp. 192-200. 

DOI: 10.1016/j.drugalcdep.2017.01.017


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States
c Department of Behavioral Sciences and Health Education, Rollins School of Public Health, Emory University, United States


Abstract
Background Little is known about marijuana advertising exposure among users in the U.S. We examined the prevalence of advertising exposure among young adult marijuana users through traditional and new media, and identified characteristics associated with seeking advertisements. Methods We conducted a cross-sectional survey of 18–34 year-old past-month marijuana users in the U.S. using a pre-existing online panel (N = 742). The survey queried about passively viewing and actively seeking marijuana advertisements in the past month, sources of advertisements, and marijuana use characteristics. Results Over half of participants were exposed to marijuana advertising in the past month (28% passively observed advertisements, 26% actively sought advertisements). Common sources for observing advertisements were digital media (i.e., social media, online, text/emails; 77%). Similarly, those actively seeking advertisements often used Internet search engines (65%) and social media (53%). Seeking advertisements was more common among those who used medically (41% medical only, 36% medical and recreational) than recreational users (18%), who used concentrates or edibles (44% and 43%) compared to those who did not (20% and 19%), and who used multiple times per day (33%) compared to those who did not (19%) (all p < 0.01). Conclusions Exposure to marijuana advertising among users is common, especially via digital media, and is associated with medical use, heavier use, and use of novel products with higher THC concentrations (i.e., concentrates) or longer intoxication duration (i.e., edibles). As the U.S. marijuana policy landscape changes, it will be important to examine potential causal associations between advertising exposure and continuation or frequency/quantity of use. © 2017 Elsevier B.V.


Author Keywords
Advertising;  Internet;  Marijuana;  Social media


Document Type: Article
Source: Scopus

 

3) 

Haspel, J.
Clocks stop sugar shock
(2017) Science Translational Medicine, 9 (384), art. no. eaan2772, . 

DOI: 10.1126/scitranslmed.aan2772


Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The circadian clock orchestrates the timing of insulin and glucagon secretion, which is important for glycemic control.


Document Type: Article
Source: Scopus

 

4) 

Greenberg, J.K.a , Yan, Y.b , Carpenter, C.R.c , Lumba-Brown, A.a d , Keller, M.S.b , Pineda, J.A.c d , Brownson, R.C.be f , Limbrick, D.D.a 
Development and internal validation of a clinical risk score for treating children with mild head trauma and intracranial injury
(2017) JAMA Pediatrics, 171 (4), pp. 342-349. 

DOI: 10.1001/jamapediatrics.2016.4520


a Department of Neurosurgery, Washington University, School of Medicine in St Louis, St Louis, MO, United States
b Department of Surgery, Washington University, School of Medicine in St Louis, St Louis, MO, United States
c Division of Emergency Medicine, Department of Neurology, Washington University School of Medicine in St Louis, St Louis, MO, United States
d Department of Pediatrics, Washington University, School of Medicine in St Louis, St Louis, MO, United States
e Alvin J Siteman Cancer Center, Washington University, School of Medicine in St Louis, St Louis, MO, United States
f Prevention Research Center, Washington University, School of Medicine in St Louis, St Louis, MO, United States


Abstract
IMPORTANCE The appropriate treatment of children with mild traumatic brain injury (mTBI) and intracranial injury (ICI) on computed tomographic imaging remains unclear. Evidence-based risk assessments may improve patient safety and reduce resource use. OBJECTIVE To derive a risk score predicting the need for intensive care unit observation in children with mTBI and ICI. DESIGN, SETTING, AND PARTICIPANTS This retrospective analysis of the prospective Pediatric Emergency Care Applied Research Network (PECARN) head injury cohort study included patients enrolled in 25 North American emergency departments from 2004 to 2006.We included patients younger than 18 years with mTBI (Glasgow Coma Scale [GCS] score, 13-15) and ICI on computed tomography. The data analysis was conducted from May 2015 to October 2016. MAIN OUTCOMES AND MEASURES The primary outcomewas the composite of neurosurgical intervention, intubation for more than 24 hours for TBI, or death from TBI. Multivariate logistic regression was used to predict the outcome. The C statistic was used to quantify discrimination, and model performance was internally validated using 10-fold cross-validation. Based on this modeling, the Children's Intracranial Injury Decision Aid score was created. RESULTS Among 15 162 children with GCS 13 to 15 head injuries who received head computed tomographic imaging in the emergency department, 839 (5.5%) had ICI. The median ages of those with and without a composite outcome were 7 and 5 years, respectively. Among those patients with ICI, 8.7%(n = 73) experienced the primary outcome, including 8.3%(n = 70) who had a neurosurgical intervention. The only clinical variable significantly associated with outcome was GCS score (odds ratio [OR], 3.4; 95%CI, 1.5-7.4 for GCS score 13 vs 15). Significant radiologic predictors included midline shift (OR, 6.8; 95%CI, 3.4-13.8), depressed skull fracture (OR, 6.5; 95%CI, 3.7-11.4), and epidural hematoma (OR, 3.4; 95%CI, 1.8-6.2). The model C statistic was 0.84 (95%CI, 0.79-0.88); the 10-fold cross-validated C statistic was 0.83. Based on this modeling, we developed the Children's Intracranial Injury Decision Aid score, which ranged from 0 to 24 points. The negative predictive value of having 0 points (ie, none of these risk factors) was 98.8% (95%CI, 97.3%-99.6%). CONCLUSIONS AND RELEVANCE Lower GCS score, midline shift, depressed skull fracture, and epidural hematoma are key risk factors for needing intensive care unit-level care in children with mTBI and ICI. Based on these results, the Children's Intracranial Injury Decision Aid score is a potentially novel tool to risk stratify this population, thereby aiding management decisions. © 2017 American Medical Association.


Document Type: Article
Source: Scopus

 

5) 

Gendron, T.F.a b , Chew, J.a b , Stankowski, J.N.a , Hayes, L.R.c , Zhang, Y.-J.a b , Prudencio, M.a b , Carlomagno, Y.a, Daughrity, L.M.a , Jansen-West, K.a , Perkerson, E.A.a , O'Raw, A.a , Cook, C.a b , Pregent, L.a , Belzil, V.a , Van Blitterswijk, M.a b , Tabassian, L.J.a , Lee, C.W.a b , Yue, M.a , Tong, J.a , Song, Y.a , Castanedes-Casey, M.a , Rousseau, L.a , Phillips, V.a , Dickson, D.W.a b , Rademakers, R.a b , Fryer, J.D.a b , Rush, B.K.d , Pedraza, O.d , Caputo, A.M.e , Desaro, P.e , Palmucci, C.e , Robertson, A.e , Heckman, M.G.f , Diehl, N.N.f , Wiggs, E.g , Tierney, M.g , Braun, L.g , Farren, J.g , Lacomis, D.h , Ladha, S.i , Fournier, C.N.j , McCluskey, L.F.k , Elman, L.B.k , Toledo, J.B.l m , McBride, J.D.m , Tiloca, C.n , Morelli, C.n , Poletti, B.n , Solca, F.n , Prelle, A.o , Wuu, J.p , Jockel-Balsarotti, J.q , Rigo, F.r , Ambrose, C.s , Datta, A.t , Yang, W.t , Raitcheva, D.u , Antognetti, G.v , McCampbell, A.w , Van Swieten, J.C.x , Miller, B.L.y , Boxer, A.L.y , Brown, R.H.z , Bowser, R.i , Miller, T.M.q , Trojanowski, J.Q.m , Grossman, M.k , Berry, J.D.aa , Hu, W.T.j , Ratti, A.n ab , Traynor, B.J.ac , Disney, M.D.ad , Benatar, M.p , Silani, V.n ab , Glass, J.D.j ae , Floeter, M.K.g , Rothstein, J.D.c , Boylan, K.B.e , Petrucelli, L.a b 
Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis
(2017) Science Translational Medicine, 9 (383), art. no. eaai7866, . 

DOI: 10.1126/scitranslmed.aai7866


a Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
b Mayo Graduate School, Mayo Clinic, Jacksonville, FL, United States
c Brain Science Institute, Department of Neurology, Johns Hopkins University, Baltimore, MD, United States
d Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, United States
e Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
f Section of Biostatistics, Mayo Clinic, Jacksonville, FL, United States
g Motor Neuron Disorders Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
h Departments of Neurology and Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
i Departments of Neurology and Neurobiology, Barrow Neurological Institute, Phoenix, AZ, United States
j Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
k Department of Neurology, Penn Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, PA, United States
l Department of Neurology, Houston Methodist Neurological Institute, Houston, TX, United States
m Center for Neurodegenerative Disease Research, Department of Pathology, Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
n Department of Neurology-Stroke Unit, Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy
o Department of Neurology and Stroke Unit, Ospedale Maggiore di Crema, Crema, Italy
p Department of Neurology, University of Miami, Miami, FL, United States
q Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
r Ionis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA, United States
s Aleta Biotherapeutics, Natick, MA, United States
t Protein Chemistry, Biogen Idec, Cambridge, MA, United States
u Global Biomarker and Drug Discovery, Biogen Idec, Cambridge, MA, United States
v Biologics Drug Discovery, Biogen Idec, Cambridge, MA, United States
w Neurology Research, Biogen Idec, Cambridge, MA, United States
x Department of Neurology, Erasmus MC, University Medical Centre, Rotterdam, Netherlands
y Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, United States
z Department of Neurology, University of Massachusetts Medical School, Worcester, MA, United States
aa Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA, United States
ab Department of Pathophysiology and Transplantation, Dino Ferrari Centre, Università Degli Studi di Milano, Milan, Italy
ac Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute of Aging, National Institutes of Health, Bethesda, MD, United States
ad Department of Chemistry, Scripps Research Institute, Scripps Florida, Jupiter, FL, United States
ae Department of Pathology, Emory University School of Medicine, Atlanta, GA, United States


Abstract
There is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease. However, discovery of a G4C2 repeat expansion in the C9ORF72 gene as the most common genetic cause of ALS has opened up new avenues for therapeutic intervention for this form of ALS. G4C2 repeat expansion RNAs and proteins of repeating dipeptides synthesized from these transcripts are believed to play a key role in C9ORF72-associated ALS (c9ALS). Therapeutics that target G4C2 RNA, such as antisense oligonucleotides (ASOs) and small molecules, are thus being actively investigated. A limitation in moving such treatments from bench to bedside is a lack of pharmacodynamic markers for use in clinical trials. We explored whether poly(GP) proteins translated from G4C2 RNA could serve such a purpose. Poly(GP) proteins were detected in cerebrospinal fluid (CSF) and in peripheral blood mononuclear cells from c9ALS patients and, notably, from asymptomatic C9ORF72 mutation carriers. Moreover, CSF poly(GP) proteins remained relatively constant over time, boding well for their use in gauging biochemical responses to potential treatments. Treating c9ALS patient cells or a mouse model of c9ALS with ASOs that target G4C2 RNA resulted in decreased intracellular and extracellular poly(GP) proteins. This decrease paralleled reductions in G4C2 RNA and downstream G4C2 RNA-mediated events. These findings indicate that tracking poly(GP) proteins in CSF could provide a means to assess target engagement of G4C2 RNA-based therapies in symptomatic C9ORF72 repeat expansion carriers and presymptomatic individuals who are expected to benefit from early therapeutic intervention. 2017 © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.


Document Type: Article
Source: Scopus

 

6) 

Harris, K.a , English, T.a , Harms, P.D.b , Gross, J.J.c , Jackson, J.J.a 
Why are Extraverts more Satisfied? Personality, Social Experiences, and Subjective Well-being in College
(2017) European Journal of Personality, 31 (2), pp. 170-186. 

DOI: 10.1002/per.2101


a Psychological & Brain Sciences, Washington University in St. LouisMO, United States
b Culverhouse College of Commerce, The University of AlabamaAL, United States
c Stanford UniversityCA, United States


Abstract
It is widely appreciated that extraversion is associated with greater subjective well-being. What is not yet clear is what mechanisms relate the two. In two longitudinal studies, we explored whether extraversion is prospectively associated with higher levels of satisfaction during college through influencing college social experiences using longitudinal cross-lagged mediation models. In both studies, students' extraversion at the beginning of college predicted their subjective well-being 4 years later. In both studies, extraversion at the beginning of college predicted a variety of self-reported and peer-reported social experiences (e.g. feelings of belonging and size of social network). We tested whether qualitative or quantitative aspects of social experiences explained the association between extraversion and subjective well-being. In the first study, neither type of social experience explained the effect of extraversion on satisfaction. Only qualitative social experiences in the second study were instrumental in explaining this effect. The results suggest that extraversion's ability to create better social experiences can play a role in extraverts' greater subjective well-being, but these experiences are not the only reason extraverts are happier and more satisfied. Copyright © 2017 European Association of Personality Psychology. Copyright © 2017 European Association of Personality Psychology


Author Keywords
extraversion;  life satisfaction;  peer relationships;  social interaction;  young adults


Document Type: Article
Source: Scopus

 

7) 

Harrington, K.D.a b , Lim, Y.Y.a c , Ames, D.d e , Hassenstab, J.f g h , Rainey-Smith, S.i j , Robertson, J.a , Salvado, O.k , Masters, C.L.a , Maruff, P.a c , AIBL Research Groupl 
Using Robust Normative Data to Investigate the Neuropsychology of Cognitive Aging
(2017) Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 32 (2), pp. 142-154. 

DOI: 10.1093/arclin/acw106


a The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
b Cooperative Research Centre (CRC) for Mental Health, Carlton South, VIC, Australia
c CogState Ltd., Melbourne, VIC, Australia
d Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia
e National Ageing Research Institute, Parkville, VIC, Australia
f Charles F. and Joanne Knight Alzheimer's Disease Research Center, St. Louis, MO, USA
g Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
h Department of Psychology, Washington University, St. Louis, MO, USA
i Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA, Australia
j Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Nedlands, WA, Australia
k CSIRO Preventative Health National Research Flagship, The Australian e-Health Research Centre-BioMedIA, Herston, QLD, Australia


Abstract
Objective: The extent to which increasing age is associated with impairment in cognitive function, termed cognitive aging, may have been overestimated in prior studies. The inclusion of individuals with severe or uncontrolled systemic medical illness or prodromal neurodegenerative disease in normal aging samples is likely to bias estimates toward lower cognitive performance and inflate estimates of variability.

Method: Unbiased estimates of cognitive aging in 658 adults aged 60-84, who underwent rigorous screening to ensure their general and cognitive health, were computed. The first study screened the psychometric properties of a battery of neuropsychological tests in order to identify those with optimal properties to evaluate cognitive aging. The second study used the selected tests to compare baseline performance within 5-year age bands from 60 to 84.

Results: The first study identified a battery of 12 tests that provided reliable measures of memory, psychomotor speed, attention, and executive function and were appropriate for investigating age-related cognitive changes. The second study observed moderate to large age-related impairment for performance on tests of complex psychomotor function, category fluency, verbal learning, and verbal and visual memory. No, or only small, age effects were observed for working memory, phonemic fluency, learning of visual information, and reaction time.

Conclusions: These data suggested that while increasing age is associated with impairment in cognitive function, this impairment is less severe and is evident only on more complex neuropsychological tests than estimated previously in samples selected using less rigorous criteria to ensure cognitive health.


Author Keywords
Assessment;  Elderly/geriatrics/aging;  Executive functions;  Fluency (verbal/nonverbal);  Learning and memory;  Norms/normative studies


Document Type: Article
Source: Scopus

 

8) 

Rice, G.I.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at , Kitabayashi, N.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at , Barth, M.a b c d e f g h ij k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at , Briggs, T.A.a b c d e f g h i j k l m n o p q rs t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at , Burton, A.C.E.a b c d e f g h i j k l m n o p q r s t u v w x yz aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at , Carpanelli, M.L.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab acad ae af ag ah ai aj ak al am an ao ap aq ar as at , Cerisola, A.M.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af agah ai aj ak al am an ao ap aq ar as at , Colson, 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A.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac adae af ag ah ai aj ak al am an ao ap aq ar as at , Uettwiller, F.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah aiaj ak al am an ao ap aq ar as at , Ulrick, N.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an aoap aq ar as at , Vanderver, A.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar asat , Waldman, A.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at , Livingston, J.H.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at , Crow, Y.J.a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at 
Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease
(2017) Neuropediatrics, . Article in Press. 

DOI: 10.1055/s-0037-1601449


a Division of Evolution and Genomic Sciences, Manchester Academic Health Science Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
b Laboratory of Neurogenetics and Neuroinflammation, INSERM UMR 1163, Paris, France
c Sorbonne-Paris-Cité, Institut Imagine, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France
d Department of Genetics, CHU Angers, Angers, France
e Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, St Mary's Hospital, Manchester, United Kingdom
f Department of Paediatrics and Child Health, St George's University Hospitals NHS Foundation Trust, London, United Kingdom
g Department of Child Neurology and Psychiatry, A. Manzoni Hospital, Lecco, Italy
h Department of Pediatric Neurology, Facultad de Medicina, UDELAR, Montevideo, Uruguay
i Clinique de Génétique, Hôpital Jeanne de Flandre, CHU Lille, Lille, France
j Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, University of Sydney, Sydney, Australia
k Department of Developmental Neurosciences, Institute of Child Health, UCL, London, United Kingdom
l Department of Neurology, Great Ormond Street Hospital, London, United Kingdom
m Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University, Rome, Italy
n Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
o Department of Pediatrics, Hospital Son Llátzer, Palma de Mallorca, Spain
p Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy
q Department of Paediatric Neurology, Royal Preston Hospital, Preston, United Kingdom
r Department of Paediatric Neurology, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
s Nutrition and metabolic Unit, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium
t Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
u Department of Paediatrics, Monash University, Melbourne, Australia
v Department of Paediatric Neurology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom
w Department of Neurology, University of California, California, San Francisco, United States
x Unit of Child Neurology and Psychiatry, Department of Clinical and Experimental Sciences, Civil Hospital, University of Brescia, Brescia, Italy
y Department of Neurology, Boston Children's Hospital, Boston, United States
z Department of Neurology, Kaiser Permanente, Los Angeles, United States
aa Neuroradiologie, CHU de Montpellier, Montpellier, France
ab General Neurology and Complex Motor Disorders Service, Evelina Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom
ac Department of Pediatrics, University of Ottawa, Ottawa, Canada
ad Department of Pediatric Neurology, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, United States
ae Medical Research, RILD Wellcome Wolfson Centre, Exeter Medical School, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
af Department of Child Neurology, Hospital Sant Joan de Déu, Esplugues de Llobregat, Catalonia, Spain
ag Department of Paediatric Neurology, Royal Manchester Children's Hospital, Manchester, United Kingdom
ah Neurogenomics Division, Center for Rare Childhood Disorders, TGen – The Translational Genomics Research Institute, Phoenix, United States
ai Department of Clinical Neurosciences for Children, and Unit for Congenital and Hereditary Neuromuscular Disorders, Oslo University Hospital, Oslo, Norway
aj Department of Neuropédiatrie and CR Maladies Neuromusculaires, CHU de Montpellier, France
ak PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France
al Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma Madrid, CIBERER, IDIPAZ, Madrid, Spain
am INSERM U1051, Institut des Neurosciences de Montpellier, Montpellier, France
an Neuropediatric Unit, Karolinska University Hospital, Stockholm, Sweden
ao Department of Pediatric Neurology, Ghaem Medical Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
ap Service de Génétique, CHU de Tours, Tours, France
aq Pediatric Immunology-Hematology and Rheumatology Unit, Institut Imagine, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France
ar Department of Allergology and Clinical Immunology, CHRU Tours, Tours, France
as Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, United States
at Department of Paediatric Neurology, Leeds General Infirmary, Leeds, United Kingdom


Abstract
We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi–Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64–25.71) compared with controls (median: 0.93, IQR: 0.57–1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context. Copyright © 2017, Georg Thieme Verlag KG. All rights reserved.


Author Keywords
Aicardi–Goutières syndrome;  bilateral striatal necrosis;  dystonia;  idiopathic basal ganglia calcification;  spastic paraparesis


Document Type: Article in Press
Source: Scopus

 

9) 

Tandon, M.
Early Childhood Mental Health: Empirical Assessment and Intervention from Conception Through Preschool
(2017) Child and Adolescent Psychiatric Clinics of North America, . Article in Press. 

DOI: 10.1016/j.chc.2017.04.001


Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8504, St Louis, MO 63110, USA


Document Type: Article in Press
Source: Scopus

 

10) 

Richmond, L.L.a , Gold, D.A.b , Zacks, J.M.a 
Improving Event Cognition: From the Laboratory to the Clinic
(2017) Journal of Applied Research in Memory and Cognition, . Article in Press. 

DOI: 10.1016/j.jarmac.2017.03.002


a Washington University in St. Louis, United States
b University Health System, Canada


Author Keywords
Activities of daily living;  Event perception;  Everyday memory;  Intervention;  Rehabilitation;  Remediation


Document Type: Article in Press
Source: Scopus

 

11) 

McDade, E.M.
Antipsychotics Use in Parkinson Disease: Separating Appropriate Therapies from Treating Inappropriately
(2017) American Journal of Geriatric Psychiatry, . Article in Press. 

DOI: 10.1016/j.jagp.2017.03.001


Department of Neurology, Washington University in Saint Louis, St. Louis, MO


Document Type: Article in Press
Source: Scopus

 

12) 

Fay, A.J.a , King, A.A.b , Shimony, J.S.c , Crow, Y.J.d e , Brunstrom-Hernandez, J.E.f 
Treatment of Leukoencephalopathy With Calcifications and Cysts With Bevacizumab
(2016) Pediatric Neurology, . Article in Press. 

DOI: 10.1016/j.pediatrneurol.2017.03.008


a Department of Neurology, University of California, San Francisco, San Francisco, California
b Program in Occupational Therapy, Division of Hematology-Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
c Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
d Faculty of Biology, Medicine and Health, Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, UK
e INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Hôpital Necker, Paris Descartes-Sorbonne Paris Cité University, Paris, France
f 1 CP Place, PLLC, Plano, Texas


Abstract
Background: Leukoencephalopathy with calcifications and cysts is a rare, autosomal recessive cerebral microangiopathy that causes progressive white matter disease, calcifications, and cysts within the brain. It is typically associated with slowly progressive psychomotor regression, seizures, and movement disorders. Although leukoencephalopathy with calcifications and cysts affects only the central nervous system, it demonstrates remarkable neuropathologic and radiologic overlap with Coats plus, a disorder of small vessels of the brain, eyes, gastrointestinal tract, and bone. Coats disease without extraocular involvement, a genetically distinct disorder from Coats plus, is characterized by retinal telangiectasias and exudative retinopathy, accompanied by neovascularization. Inhibition of vascular endothelial growth factor (VEGF) signaling with the monoclonal anti-VEGF antibody bevacizumab can improve retinal edema and exudates in Coats disease. Given these observations, we reasoned that VEGF inhibition might also be effective in treating leukoencephalopathy with calcifications and cysts and Coats plus, neither of which has any known therapy. Methods: We treated an 18-year-old man with leukoencephalopathy with calcifications and cysts using biweekly infusions of the VEGF inhibitor bevacizumab for more than one year and performed clinical examinations and brain imaging at three month intervals. Results: After treatment for more than one year, the patient showed improved bradykinesia and range of motion, and brain magnetic resonance imaging demonstrated a marked reduction in cyst volume and white matter lesions. Conclusions: Further studies in a cohort of patients are warranted to investigate the efficacy of VEGF inhibition as a treatment for leukoencephalopathy with calcifications and cysts. © 2017 Elsevier Inc.


Author Keywords
Cerebrovascular disease;  Developmental disorders;  Genetics;  Leukodystrophy;  Movement disorders


Document Type: Article in Press
Source: Scopus