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

Neuroscience Publications Archive - August 2017

Scopus Weekly Report:

August 28, 2017

August 7, 2017

 

August 28, 2017 

1) 

Fanizzi, C., Sauerbeck, A.D., Gangolli, M., Zipfel, G.J., Brody, D.L., Kummer, T.T.
Minimal long-term neurobehavioral impairments after endovascular perforation subarachnoid hemorrhage in mice
(2017) Scientific Reports, 7 (1), art. no. 7569, . 

DOI: 10.1038/s41598-017-07701-y


a Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Neurosurgery, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy


Abstract
Cognitive deficits are among the most severe and pervasive consequences of aneurysmal subarachnoid hemorrhage (SAH). A critical step in developing therapies targeting such outcomes is the characterization of experimentally-tractable pre-clinical models that exhibit multi-domain neurobehavioral deficits similar to those afflicting humans. We therefore searched for neurobehavioral abnormalities following endovascular perforation induction of SAH in mice, a heavily-utilized model. We instituted a functional screen to manage variability in injury severity, then assessed acute functional deficits, as well as activity, anxiety-related behavior, learning and memory, socialization, and depressive-like behavior at sub-acute and chronic time points (up to 1 month post-injury). Animals in which SAH was induced exhibited reduced acute functional capacity and reduced general activity to 1 month post-injury. Tests of anxiety-related behavior including central area time in the elevated plus maze and thigmotaxis in the open field test revealed increased anxiety-like behavior at subacute and chronic time-points, respectively. Effect sizes for subacute and chronic neurobehavioral endpoints in other domains, however, were small. In combination with persistent variability, this led to non-significant effects of injury on all remaining neurobehavioral outcomes. These results suggest that, with the exception of anxiety-related behavior, alternate mouse models are required to effectively analyze cognitive outcomes after SAH. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

2) 

Kang, P., Schmidt, R.E., Dahiya, S., Varadhachary, A.S.
A 42-Year-Old Man with AIDS and Multiple Incomplete Ring Enhancing Lesions
(2017) Brain Pathology, 27 (5), pp. 697-698. 

DOI: 10.1111/bpa.12542


a Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
b Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States


Document Type: Article
Source: Scopus

 

3) 

Lanctôt, K.L., Amatniek, J., Ancoli-Israel, S., Arnold, S.E., Ballard, C., Cohen-Mansfield, J., Ismail, Z., Lyketsos, C., Miller, D.S., Musiek, E., Osorio, R.S., Rosenberg, P.B., Satlin, A., Steffens, D., Tariot, P., Bain, L.J., Carrillo, M.C., Hendrix, J.A., Jurgens, H., Boot, B.
Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment paradigms
(2017) Alzheimer's and Dementia: Translational Research and Clinical Interventions, 3 (3), pp. 440-449. 

DOI: 10.1016/j.trci.2017.07.001


a Hurvitz Brain Sciences Program, Sunnybrook Research Institute and Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Canada
b Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, United States
c Department of Psychiatry, University of California, San Diego, CA, United States
d Department of Medicine, University of California, San Diego, CA, United States
e Interdisciplinary Brain Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States
f Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
g University of Exeter, Exeter, United Kingdom
h Department of Health Promotion, School of Public Health, Sackler Faculty of Medicine and Minerva Center for the Interdisciplinary Study of End of Life, Tel Aviv University, Tel Aviv, Israel
i Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
j Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medicine Institutes, Baltimore, MD, United States
k Bracket Global, Wayne, PA, United States
l Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
m Center for Brain Health, NYU Langone Medical Center, New York, NY, United States
n Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
o Eisai, Inc., Woodcliff Lake, NJ, United States
p Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, United States
q Banner Alzheimer's Institute, Phoenix, AZ, United States
r Elverson, PA, United States
s Alzheimer's Association, Chicago, IL, United States
t Department of Neurology, Brigham and Women's Hospital, Harvard University School of Medicine, Boston, MA, United States
u Voyager Therapeutics, Cambridge, MA, United States


Abstract
Neuropsychiatric symptoms (NPSs) are hallmarks of Alzheimer's disease (AD), causing substantial distress for both people with dementia and their caregivers, and contributing to early institutionalization. They are among the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, yet are under-recognized and often challenging to treat. With this in mind, the Alzheimer's Association convened a Research Roundtable in May 2016, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of NPSs and review the development of therapeutics and biomarkers of NPSs in AD. This review will explore the neurobiology of NPSs in AD and specific symptoms common in AD such as psychosis, agitation, apathy, depression, and sleep disturbances. In addition, clinical trial designs for NPSs in AD and regulatory considerations will be discussed. © 2017 The Authors


Author Keywords
Agitation;  Alzheimer's disease;  Apathy;  Delusions;  Depression;  Hallucinations;  Neuropsychiatric symptoms;  Sleep disturbance;  Trial design


Document Type: Review
Source: Scopus

 

4) 

Limbrick Jr, D.D., Castaneyra-Ruiz, L., Han, R.H., Berger, D., McAllister, J.P., Morales, D.M.
Cerebrospinal Fluid Biomarkers of Pediatric Hydrocephalus
(2017) Pediatric Neurosurgery, . Article in Press. 

DOI: 10.1159/000477175


Division of Pediatric Neurosurgery, Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA


Abstract
Hydrocephalus (HC) is a common, debilitating neurological condition that requires urgent clinical decision-making. At present, neurosurgeons rely heavily on a patient's history, physical examination findings, neuroimaging, and clinical judgment to make the diagnosis of HC or treatment failure (e.g., shunt malfunction). Unfortunately, these tools, even in combination, do not eliminate subjectivity in clinical decisions. In order to improve the management of infants and children with HC, there is an urgent need for new biomarkers to complement currently available tools and enable clinicians to confidently establish the diagnosis of HC, assess therapeutic efficacy/treatment failure, and evaluate current and future developmental challenges, so that every child has access to the resources they need to optimize their outcome and quality of life. © 2017 S. Karger AG, Basel


Author Keywords
Biomarker;  Cerebrospinal fluid;  Congenital hydrocephalus;  Hydrocephalus;  Intraventricular hemorrhage;  Posthemorrhagic hydrocephalus


Document Type: Article in Press
Source: Scopus

 

5) 

Aisen, P.S., Cummings, J., Jack, C.R., Jr., Morris, J.C., Sperling, R., Frölich, L., Jones, R.W., Dowsett, S.A., Matthews, B.R., Raskin, J., Scheltens, P., Dubois, B.
On the path to 2025: Understanding the Alzheimer's disease continuum
(2017) Alzheimer's Research and Therapy, 9 (1), art. no. 60, . 

DOI: 10.1186/s13195-017-0283-5


a University of Southern California, San Diego, CA, United States
b Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
c Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
d Department of Radiology, Mayo Clinic, Rochester, MN, United States
e Research Institute for the Care of Older People (RICE), Royal United Hospital, Bath, United Kingdom
f Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO, United States
g Center for Alzheimer's Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
h Eli Lilly and Company, Indianapolis, IN, United States
i Eli Lilly Canada Inc., Toronto, ON, Canada
j Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, Netherlands
k Institute for Memory and Alzheimer's Disease (IM2A) and ICM, Salpêtrière University Hospital, Paris University (UPMC), Paris, France


Abstract
Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer's disease (AD). It is now recognized that pathophysiological changes begin many years prior to clinical manifestations of disease and the spectrum of AD spans from clinically asymptomatic to severely impaired. Defining AD purely by its clinical presentation is thus artificial and efforts have been made to recognize the disease based on both clinical and biomarker findings. Advances with biomarkers have also prompted a shift in how the disease is considered as a clinico-pathophysiological entity, with an increasing appreciation that AD should not only be viewed with discrete and defined clinical stages, but as a multifaceted process moving along a seamless continuum. Acknowledging this concept is critical to understanding the development process for disease-modifying therapies, and for initiating effective diagnostic and disease management options. In this article, we discuss the concept of a disease continuum from pathophysiological, biomarker, and clinical perspectives, and highlight the importance of considering AD as a continuum rather than discrete stages. While the pathophysiology of AD has still not been elucidated completely, there is ample evidence to support researchers and clinicians embracing the view of a disease continuum in their study, diagnosis, and management of the disease. © 2017 The Author(s).


Author Keywords
Alzheimer's disease;  Amyloid beta;  Biomarker;  Clinical;  Cognitive impairment;  Continuum;  Dementia;  Tau


Document Type: Review
Source: Scopus

 

6) 

Haspel, J.
Mind your bedtime: The circadian clock and mTOR in an orphan brain disease
(2017) Science Translational Medicine, 9 (402), art. no. aao2261, . 

DOI: 10.1126/scitranslmed.aao2261


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


Document Type: Note
Source: Scopus

 

7) 

Wright, N.C., Hoseini, M.S., Wessel, R.
Adaptation modulates correlated subthreshold response variability in visual cortex
(2017) Journal of Neurophysiology, 118 (2), pp. 1257-1269. 

DOI: 10.1152/jn.00124.2017


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


Abstract
Cortical sensory responses are highly variable across stimulus presentations. This variability can be correlated across neurons (due to some combination of dense intracortical connectivity, cortical activity level, and cortical state), with fundamental implications for population coding. Yet the interpretation of correlated response variability (or “noise correlation”) has remained fraught with difficulty, in part because of the restriction to extracellular neuronal spike recordings. Here, we measured response variability and its correlation at the most microscopic level of electrical neural activity, the membrane potential, by obtaining dual whole cell recordings from pairs of cortical pyramidal neurons during visual processing in the turtle whole brain ex vivo preparation. We found that during visual stimulation, correlated variability adapts toward an intermediate level and that this correlation dynamic is likely mediated by intracortical mechanisms. A model network with external inputs, synaptic depression, and structure reproduced the observed dynamics of correlated variability. These results suggest that intracortical adaptation self-organizes cortical circuits toward a balanced regime at which correlated variability is maintained at an intermediate level. NEW & NOTEWORTHY Correlated response variability has profound implications for stimulus encoding, yet our understanding of this phenomenon is based largely on spike data. Here, we investigate the dynamics and mechanisms of membrane potential-correlated variability (CC) in visual cortex with a combined experimental and computational approach. We observe a visually evoked increase in CC, followed by a fast return to baseline. Our results further suggest a link between this observation and the adaptation-mediated dynamics of emergent network phenomena. © 2017 the American Physiological Society.


Author Keywords
Adaptation;  Correlated variability;  Cortex;  Membrane potential;  Oscillations


Document Type: Article
Source: Scopus

 

8) 

Berg, C.J., Payne, J., Henriksen, L., Cavazos-Rehg, P., Getachew, B., Schauer, G.L., Haardörfer, R.
Reasons for Marijuana and Tobacco Co-use Among Young Adults: A Mixed Methods Scale Development Study
(2017) Substance Use and Misuse, pp. 1-13. Article in Press. 

DOI: 10.1080/10826084.2017.1327978


a Department of Behavioral Sciences and Health Education, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
b Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA
c Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
d Department of Health Services, School of Public Health, University of Washington, Seattle, Washington, USA


Abstract
Background: Marijuana-tobacco co-use has increased recently, particularly in young adults. Objectives: We conducted a mixed-methods study to: (1) examine reasons for co-use; and (2) develop a scale assessing reasons for co-use among participants in a longitudinal cohort study of 3,418 students aged 18-25 from 7 Georgia colleges and universities. Methods: Phone-based semi-structured interviews were conducted in Summer 2015 among 46 current (past 30-day, n = 26) or lifetime (n = 20) marijuana users. Subsequently, scale items were developed and included at Wave 3. Participants reporting past 4-month tobacco and marijuana use (n = 328) completed the Reasons for Marijuana-Tobacco Co-use section. Results: Per qualitative data, reasons for marijuana-tobacco co-use included synergistic effects, one triggering or preceding the other's use, using one to reduce the other's use, co-administration, social context, and experimentation. The survey subsample included 37.1% who used cigarettes, 30.4% LCCs, 9.4% smokeless, 23.7% e-cigarettes, and 30.4% hookah. Four subscale factors emerged: (1) Instrumentality, indicating synergistic effects; (2) Displacement, indicating using one product to reduce/quit the other; (3) Social context, indicating use in different settings/social situations; and (4) Experimentation, indicating experimentation with both but no specific reasons for co-use. These subscales demonstrated distinct associations with tobacco type used; nicotine dependence; marijuana and alcohol use frequency; tobacco and marijuana use motives, respectively; perceptions of tobacco and marijuana; and parental and friend use. Including these subscales in regressions predicting nicotine dependence and days of marijuana use significantly contributed to each model. Conclusions: These findings might inform theoretical frameworks upon which marijuana-tobacco co-use occurs and direct future intervention studies. © 2017 Taylor & Francis Group, LLC


Author Keywords
marijuana use;  risk factors;  Substance use;  tobacco use;  young adults


Document Type: Article in Press
Source: Scopus

 

9) 

Sharma, A., Sargar, K., Salter, A.
Temporal evolution of disc in young patients with low back pain and stress reaction in lumbar vertebrae
(2017) American Journal of Neuroradiology, 38 (8), pp. 1647-1652. 

DOI: 10.3174/ajnr.A5237


a Mallinckrodt Institute of Radiology, Washington University, School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, United States
b Department of Biostatistics, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Radiology, Barnes-Jewish Hospital South, St. Louis, MO, United States
d Department of Radiology, St. Louis Children's Hospital, St. Louis, MO, United States


Abstract
BACKGROUNDANDPURPOSE: Although stress-induced bony changes often resolve with conservative treatment, the long-term effects of such mechanical stresses on intervertebral discs have not been studied. We aimed to assess the differences in the temporal evolution of disc in segments of the lumbar spine with and without signs of increased mechanical stresses. MATERIALS AND METHODS: Using MR imaging performed >6 months apart, 2 radiologists evaluated lumbar intervertebral discs for degenerative changes affecting the annulus fibrosus, the nucleus pulposus, and the endplates in 42 patients (22 male, 20 female; mean age, 16.0 ± 3.7 years [range, 7-25 years]) with low back pain and imaging evidence of stress reaction/fracture in the lumbar spine. Data were analyzed for differences in the presence and progression of disc degeneration in stressed versus nonstressed segments. RESULTS: At baseline, stressed discs had a higher burden of annular fissures, radial fissures, herniation, and nuclear degeneration. Endplate defect burden was comparable in stressed and control discs. At follow-up, the burden of new annular fissures and endplate defects was comparable for stressed and control discs. However, a higher proportion of stressed discs showed worsening nuclear signal intensity grade (14.3% versus 0% control discs; P = .008) and worsening nuclear degeneration grade (11.9% versus 0% control discs; P = .02). An increased risk of progressive nuclear degeneration of stressed discs was observed irrespective of the outcome of bony changes. CONCLUSIONS: Stressed discs exhibit a higher burden of nuclear and annular degeneration at baseline. These discs have a higher risk of progressive nuclear degeneration irrespective of improvement or worsening of stress-related bony changes.


Document Type: Article
Source: Scopus

 

10) 

Wallace, A.N., Hillen, T.J., Friedman, M.V., Zohny, Z.S., Stephens, B.H., Greco, S.C., Talcott, M.R., Jennings, J.W.
Percutaneous spinal ablation in a sheep model: Protective capacity of an intact cortex, correlation of ablation parameters with ablation zone size, and correlation of postablation MRI and pathologic findings
(2017) American Journal of Neuroradiology, 38 (8), pp. 1653-1659. 

DOI: 10.3174/ajnr.A5228


a Mallinckrodt Institute of Radiology, Washington University, 510 South Kingshighway Blvd, St Louis, MO, United States
b Department of Neurosurgery, Washington University, St Louis, MO, United States
c Division of Comparative Medicine, Washington University, St Louis, MO, United States


Abstract
BACKGROUND AND PURPOSE: Despite the growing use of percutaneous ablation therapy for the treatment of metastatic spine disease, several issues have yet to be fully addressed. Our aims were to determine whether the vertebral body cortex protects against ablationinduced spinal cord injury; correlate radiofrequency, cryo-, and microwave ablation parameters with resulting spinal ablation zone dimensions and describe normal spinal marrow postablation changes on MR imaging. MATERIALS AND METHODS: Ten thoracolumbar vertebrae in 3 sheep were treated with radiofrequency ablation, cryoablation, or microwave ablation under fluoroscopic guidance. Technique parameters were chosen to produce ablation zones that exceeded the volume of the vertebral bodies in sheep 1 and were confined to the vertebrae in sheep 2 and 3. Expected ablation zone dimensions were based on data provided by the device manufacturers. Postablation MR imaging was performed at 48 hours (sheep 1) or 7 days (sheep 2 and 3). RESULTS: In sheep 1, cryoablation and microwave ablations extended into the spinal canal and caused histologically confirmed neurologic injury, but radiofrequency ablation did not. The mean difference between the lengths of the radiofrequency ablation zone dimensions measured on gross pathology compared with those expected was 9.6±4.1 mm. The gross pathologic cryo- and microwave ablation zone dimensions were within 1 mm of those expected. All modalities produced a nonenhancing ablation zone with a rim of enhancement, corresponding histologically to marrow necrosis and hemorrhagic congestion. CONCLUSIONS: An intact cortex appears to protect against radiofrequency ablation-induced spinal cord injury, but not against nonimpedance- based modalities. Ablation dimensions produced by microwave and cryoablation are similar to those expected, while radiofrequency ablation dimensions are smaller. Ablation of normal marrow produces a rim of enhancement at the margin of the ablation zone on MR imaging.


Document Type: Article
Source: Scopus

 

11) 

McCall, J.G., Siuda, E.R., Bhatti, D.L., Lawson, L.A., McElligott, Z.A., Stuber, G.D., Bruchas, M.R.
Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior
(2017) eLife, 6, art. no. e18247, . 

DOI: 10.7554/eLife.18247


a Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, United States
b Washington University Pain Center, Washington University School of Medicine, St. Louis, United States
c Department of Neuroscience, Washington University School of Medicine, St. Louis, United States
d Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, United States
e Department of Psychiatry, University of North Carolina, Chapel Hill, United States
f Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, United States
g Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, United States
h Neuroscience Center, University of North Carolina, Chapel Hill, United States
i Department of Biomedical Engineering, Washington University, St. Louis, United States
j Department of Anesthesiology, Washington University, St. Louis, United States
k Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, United States
l Center for Clinical Pharmacology, Washington University School of Medicine, St. Louis College of Pharmacy, St. Louis, United States
m Trevena Inc., King of Prussia, United States


Abstract
Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms. © McCall et al.


Document Type: Article
Source: Scopus

 

12) 

Goldberg, R.L., Piccirillo, M.L., Nicklaus, J., Skillington, A., Lenze, E., Rodebaugh, T.L., Kallogjeri, D., Piccirillo, J.F.
Evaluation of ecological momentary assessment for tinnitus severity
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (7), pp. 700-706. 

DOI: 10.1001/jamaoto.2017.0020


a Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, MO, United States
b Department of Psychology, Washington University in St Louis, St Louis, MO, United States
c AbbVie Clinical Pharmacology Research Unit, Chicago, IL, United States
d Healthy Mind Lab., Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, United States


Abstract
IMPORTANCE: Existing patient-reported outcome measures of tinnitus assess the severity and disability retrospectively, which may result in adequate reliability, but cannot capture the fluctuating and individualized nature of tinnitus. Experience sampling may provide an alternative. OBJECTIVE: To use an ecological momentary assessment (EMA) to measure tinnitus disability and associated constructs. DESIGN, SETTING, AND PARTICIPANTS: Forty adults with tinnitus provided self-report of their tinnitus bother using 5 questions measured by EMA, as well as standard retrospective outcome measures. In this 6-week longitudinal observational study conducted from July 15 to December 22, 2014, participants provided EMA data for 2 weeks (part 1); then after a 2-week break, they provided EMA data for an additional 2 weeks (part 2). A text message with a link to the EMA survey was sent for a total of 56 assessments during each 2-week assessment period. Ecological momentary assessment responses were evaluated using multilevel confirmatory factor analysis to assess the fluctuating nature of bothersome tinnitus across the group and within the pool of individuals over time. MAIN OUTCOMES AND MEASURES: Ecological momentary assessment questions measured tinnitus disability and associated constructs. Compliance in each study part was assessed based on response rates. The Tinnitus Functional Index and the Overall Global Rating of Bother Scale were assessed at the beginning and end of each 2-week assessment period to explore the effect of the frequent EMAs on the perceived level of bother from tinnitus. RESULTS: Of the 40 participants in the study (10 women and 30 men; mean [SD] age, 60.0 [10.5] years), the median survey response rate was high (49 responses to 56 surveys sent [88%] for part 1 and 47 responses of 56 surveys sent [84%] for part 2). The latent factor identified by the 2-level confirmatory factor analysis models demonstrates that within-individual tinnitus bother, loudness, and stress vary together over time. In addition, tinnitus bother, feeling, and stress symptoms all vary together across individuals, which means that bother and stress covary strongly both across time and across individuals. CONCLUSIONS AND RELEVANCE: Ecological momentary assessment evaluates the moment-to-moment perception of tinnitus and the effect of emotional and environmental factors, which suggests that it is a superior tool to measure tinnitus outcomes compared with standard retrospective self-reports. Taken together, information from emotional and environmental factors can be summarized in an underlying (latent) factor that represents a vulnerability to bothersome tinnitus and that can be used to comprehensively describe the tinnitus experience. Momentary variability in tinnitus bother is strongly associated with levels of perceived stress. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus

 

13) 

Valente, M., Amlani, A.M.
Cost as a barrier for hearing aid adoption
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (7), pp. 647-648. 

DOI: 10.1001/jamaoto.2017.0245


a School of Medicine, Washington University in St Louis, St Louis, MO, United States
b Department of Audiology and Speech Pathology, Consortium Program between University of Arkansas for Medical Sciences, University of Arkansas at Little Rock, Little Rock, United States


Document Type: Short Survey
Source: Scopus

 

14) 

Nandi, A., Schattler, H., Ching, S.
Selective spiking in neuronal populations
(2017) Proceedings of the American Control Conference, art. no. 7963377, pp. 2811-2816. 

DOI: 10.23919/ACC.2017.7963377


a Faculty of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, United States
b Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, United States


Abstract
The use of extrinsic stimulation to control activity in neuronal networks i.e., neurocontrol, is a key problem in control engineering and neuroscience. Here, we study the general problem of selective spiking in a population of neurons. The goal is to use an input stimulus in order to induce a spike in a specific neuron of a population while keeping all others suppressed. We formulate a strict version of this problem for the class of Integrate-and-Fire neuron models, which amounts to an optimal control problem with state constraints. While possible to solve in low dimensions, the strict problem is harder to handle for larger networks. Thus, we relax the problem via regularization and derive the ensuing optimal controls for selective spiking. The properties of the solution are highlighted through several examples. The results provide a tractable, scalable solution for a baseline neurocontrol problem. © 2017 American Automatic Control Council (AACC).


Document Type: Conference Paper
Source: Scopus

 

15) 

Huang, F., Riehl, J., Ching, S.
Optimizing the dynamics of spiking networks for decoding and control
(2017) Proceedings of the American Control Conference, art. no. 7963374, pp. 2792-2798. 

DOI: 10.23919/ACC.2017.7963374


Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States


Abstract
In this paper, an optimization-based approach to construct spiking networks for the purposes of decoding and control is presented. Specifically, we postulate a simple objective function wherein a network of interacting, primitive spiking units is decoded in order to drive a linear system along a prescribed trajectory. The units are assumed to spike only if doing so will decrease a specified objective function. The optimization gives rise to an emergent network of neurons with diffusive dynamics and a threshold-based spiking rule that bears resemblance to the Integrate and Fire neural model. © 2017 American Automatic Control Council (AACC).


Document Type: Conference Paper
Source: Scopus

 

16) 

Vinberg, F., Wang, T., De Maria, A., Zhao, H., Bassnett, S., Chen, J., Kefalov, V.J.
The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision
(2017) eLife, 6, art. no. e24550, . 

DOI: 10.7554/eLife.24550


a Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, United States
b Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, United States
c Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, United States
d Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, United States
e Department of Biology, Johns Hopkins University, Baltimore, United States


Abstract
Calcium (Ca2+) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca2+ controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca2+ in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na+/Ca2+, K+ exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision. We show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2: NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca2+ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promotes their survival. © 2017. Verasztó et al.


Document Type: Article
Source: Scopus

 

17) 

Schoch, K.M., Miller, T.M.
Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases
(2017) Neuron, 94 (6), pp. 1056-1070. 

DOI: 10.1016/j.neuron.2017.04.010


Department of Neurology, Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA


Abstract
Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression. ASOs are ideal candidates for the treatment of neurodegenerative diseases, given numerous advancements made to their chemical modifications and delivery methods. Successes achieved in both animal models and human clinical trials have proven ASOs both safe and effective. With proper considerations in mind regarding the human applicability of ASOs, we anticipate ongoing in vivo research and clinical trial development of ASOs for the treatment of neurodegenerative diseases. Copyright © 2017 Elsevier Inc. All rights reserved.


Author Keywords
antisense oligonucleotides;  clinical trial;  in vivo models;  neurodegeneration;  therapy


Document Type: Review
Source: Scopus

 

18) 

Chen, R., Pan, Y., Gutmann, D.H.
The power of the few
(2017) Genes and Development, 31 (12), pp. 1177-1179. 

DOI: 10.1101/gad.303453.117


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


Abstract
Converging evidence from numerous laboratories has revealed that malignant brain cancers are complex ecological systems composed of distinct cellular and acellular elements that collectively dictate glioblastoma biology. Our understanding of the individual contributions of each of these components is vital to the design of effective therapies against these cancers. In this issue of Genes & Development, Zanca and colleagues (pp. 1212-1227) demonstrate that one subpopulation of glioblastoma cells expressing a mutant epidermal growth factor receptor (EGFRvIII) is responsible for the survival of non-EGFR-vIII-expressing tumor cells as well as for evading molecularly targeted therapy. © 2017 Chen et al.


Author Keywords
EGFR;  Glioblastoma;  IL-6;  NF-κB;  Survivin;  Tumor heterogeneity


Document Type: Article
Source: Scopus

 

19) 

Chew, K.S., Renna, J.M., McNeill, D.S., Fernandez, D.C., Keenan, W.T., Thomsen, M.B., Ecker, J.L., Loevinsohn, G.S., Vandunk, C., Vicarel, D.C., Tufford, A., Weng, S., Gray, P.A., Cayouette, M., Herzog, E.D., Zhao, H., Berson, D.M., Hattar, S.
A subset of iprgcs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice
(2017) eLife, 6, art. no. e22861, . 

DOI: 10.7554/eLife.22861


a Department of Biology, Johns Hopkins University, Baltimore, United States
b Department of Biology, Stanford University, Stanford, United States
c Department of Biology, The University of Akron, Akron, United States
d Department of Neuroscience, Brown University, Providence, United States
e Department of Anatomy and Neurobiology, Washington University, St. Louis, United States
f Department of Neurobiology, Northwestern University, Evanston, United States
g Cellular Neurobiology Research Unit, Institut De Recherches Cliniques De Montréal, Montreal, Canada
h Indigo Agriculture, Charlestown, United States
i Faculty of Medicine, Université De Montréal, Montreal, Canada
j Department of Biology, Washington University, St. Louis, United States
k Section on Light and Circadian Rhythms, National Institute of Mental Health, National Institute of Health, Bethesda, United States


Abstract
The visual system consists of two major subsystems, image-forming circuits that drive conscious vision and non-image-forming circuits for behaviors such as circadian photoentrainment. While historically considered non-overlapping, recent evidence has uncovered crosstalk between these subsystems. Here, we investigated shared developmental mechanisms. We revealed an unprecedented role for light in the maturation of the circadian clock and discovered that intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for this refinement process. In addition, ipRGCs regulate retinal waves independent of light, and developmental ablation of a subset of ipRGCs disrupts eye-specific segregation of retinogeniculate projections. Specifically, a subset of ipRGCs, comprising ~200 cells and which project intraretinally and to circadian centers in the brain, are sufficient to mediate both of these developmental processes. Thus, this subset of ipRGCs constitute a shared node in the neural networks that mediate light-dependent maturation of the circadian clock and light-independent refinement of retinogeniculate projections. © 2017. Verasztó et al.


Document Type: Article
Source: Scopus

 

20) 

Garabedian, M.J., Harris, C.A., Jeanneteau, F.
Glucocorticoid receptor action in metabolic and neuronal function
(2017) F1000Research, 6, art. no. 1208, . 

DOI: 10.12688/f1000research.11375.1


a Department of Microbiology, New York University School of Medicine, Alexandria Center for Life Sciences, 450 East 29th Street, New York, NY, United States
b Department of Internal Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, United States
c Departments of Physiology and Neuroscience, Institute of Functional Genomics, INSERM U1191, CNRS UMR5203, University of Montpellier, Montpellier, France


Abstract
Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture-based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this "brain-fat axis" will enable a more complete understanding of metabolic diseases and inform new ways to target them. © 2017 Garabedian MJ et al.


Author Keywords
Glucocorticoid receptor;  Glucocorticoid receptor ligands;  Glucocorticoid receptor phosphorylation;  Glucocorticoid receptors in the brain;  Glucocorticoids


Document Type: Review
Source: Scopus

 

August 7, 2017 

1) 

Benitez, B.A., Sands, M.S.
Primary fibroblasts from CSPα mutation carriers recapitulate hallmarks of the adult onset neuronal ceroid lipofuscinosis
(2017) Scientific Reports, 7 (1), art. no. 6332, . 

DOI: 10.1038/s41598-017-06710-1


a Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Mutations in the co-chaperone protein, CSPα, cause an autosomal dominant, adult-neuronal ceroid lipofuscinosis (AD-ANCL). The current understanding of CSPα function exclusively at the synapse fails to explain the autophagy-lysosome pathway (ALP) dysfunction in cells from AD-ANCL patients. Here, we demonstrate unexpectedly that primary dermal fibroblasts from pre-symptomatic mutation carriers recapitulate in vitro features found in the brains of AD-ANCL patients including auto-fluorescent storage material (AFSM) accumulation, CSPα aggregates, increased levels of lysosomal proteins and lysosome enzyme activities. AFSM accumulation correlates with CSPα aggregation and both are susceptible to pharmacological modulation of ALP function. In addition, we demonstrate that endogenous CSPα is present in the lysosome-enriched fractions and co-localizes with lysosome markers in soma, neurites and synaptic boutons. Overexpression of CSPα wild-type (WT) decreases lysotracker signal, secreted lysosomal enzymes and SNAP23-mediated lysosome exocytosis. CSPα WT, mutant and aggregated CSPα are degraded mainly by the ALP but this disease-causing mutation exhibits a faster rate of degradation. Co-expression of both WT and mutant CSPα cause a block in the fusion of autophagosomes/lysosomes. Our data suggest that aggregation-dependent perturbation of ALP function is a relevant pathogenic mechanism for AD-ANCL and supports the use of AFSM or CSPα aggregation as biomarkers for drug screening purposes. © 2017 The Author(s).


Document Type: Article
Source: Scopus




2) 

Monosov, I.E.
Anterior cingulate is a source of valence-specific information about value and uncertainty
(2017) Nature Communications, 8 (1), art. no. 134, . 

DOI: 10.1038/s41467-017-00072-y


Departments of Neuroscience and Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Anterior cingulate cortex (ACC) is thought to control a wide range of reward, punishment, and uncertainty-related behaviors. However, how it does so is unclear. Here, in a Pavlovian procedure in which monkeys displayed a diverse repertoire of reward-related, punishment-related, and uncertainty-related behaviors, we show that many ACC-neurons represent expected value and uncertainty in a valence-specific manner, signaling value or uncertainty predictions about either rewards or punishments. Other ACC-neurons signal prediction information about rewards and punishments by displaying excitation to both (rather than excitation to one and inhibition to the other). This diversity in valence representations may support the role of ACC in many behavioral states that are either enhanced by reward and punishment (e.g., vigilance) or specific to either reward or punishment (e.g., approach and avoidance). Also, this first demonstration of punishment-uncertainty signals in the brain suggests that ACC could be a target for the treatment of uncertainty-related disorders of mood. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

3) 

Keefer, K.M., Stein, K.C., True, H.L.
Heterologous prion-forming proteins interact to cross-seed aggregation in Saccharomyces cerevisiae
(2017) Scientific Reports, 7 (1), art. no. 5853, . 

DOI: 10.1038/s41598-017-05829-5


a Department of Cell Biology and Physiology, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Biology, Stanford University, Stanford, CA, United States


Abstract
The early stages of protein misfolding remain incompletely understood, as most mammalian proteinopathies are only detected after irreversible protein aggregates have formed. Cross-seeding, where one aggregated protein templates the misfolding of a heterologous protein, is one mechanism proposed to stimulate protein aggregation and facilitate disease pathogenesis. Here, we demonstrate the existence of cross-seeding as a crucial step in the formation of the yeast prion [PSI +], formed by the translation termination factor Sup35. We provide evidence for the genetic and physical interaction of the prion protein Rnq1 with Sup35 as a predominant mechanism leading to self-propagating Sup35 aggregation. We identify interacting sites within Rnq1 and Sup35 and determine the effects of breaking and restoring a crucial interaction. Altogether, our results demonstrate that single-residue disruption can drastically reduce the effects of cross-seeding, a finding that has important implications for human protein misfolding disorders. © 2017 The Author(s).


Document Type: Article
Source: Scopus

 

4) 

Hassanpour, M.S., Eggebrecht, A.T., Peelle, J.E., Culvera, J.P.
Mapping effective connectivity within cortical networks with diffuse optical tomography
(2017) Neurophotonics, 4 (4), art. no. 041402, . 

DOI: 10.1117/1.NPh.4.4.041402


a Washington University in St. Louis, Department of Physics, St. Louis, MO, United States
b Washington University in St. Louis, Department of Radiology, St. Louis, MO, United States
c Washington University in St. Louis, Department of Otolaryngology, St. Louis, MO, United States
d Washington University in St. Louis, Department of Biomedical Engineering, St. Louis, MO, United States


Abstract
Understanding how cortical networks interact in response to task demands is important both for providing insight into the brain's processing architecture and for managing neurological diseases and mental disorders. High-density diffuse optical tomography (HD-DOT) is a neuroimaging technique that offers the significant advantages of having a naturalistic, acoustically controllable environment and being compatible with metal implants, neither of which is possible with functional magnetic resonance imaging. We used HD-DOT to study the effective connectivity and assess the modulatory effects of speech intelligibility and syntactic complexity on functional connections within the cortical speech network. To accomplish this, we extend the use of a generalized psychophysiological interaction (PPI) analysis framework. In particular, we apply PPI methods to event-related HD-DOT recordings of cortical oxyhemoglobin activity during auditory sentence processing. We evaluate multiple approaches for selecting cortical regions of interest and for modeling interactions among these regions. Our results show that using subject-based regions has minimal effect on group-level connectivity maps. We also demonstrate that incorporating an interaction model based on estimated neural activity results in significantly stronger effective connectivity. Taken together our findings support the use of HD-DOT with PPI methods for noninvasively studying task-related modulations of functional connectivity. © 2017 The Authors.


Author Keywords
Diffuse optical tomography;  Effective connectivity;  Psychophysiological interaction;  Speech comprehension


Document Type: Article
Source: Scopus

 

5) 

Bailey, R.R.
Promoting physical activity and nutrition in people with stroke
(2017) American Journal of Occupational Therapy, 71 (5), art. no. 7105360010, . 

DOI: 10.5014/ajot.2017.021378


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


Abstract
The prevalence of cardiovascular disease, diabetes, and obesity is high in people with stroke. Risk factors for these conditions include hypertension, high cholesterol, and physical inactivity. These risk factors are common in people with stroke and often go unmanaged. Engagement in healthy behaviors is important for managing and preventing these risk factors and comorbid conditions. More specifically, physical activity and nutrition are key health behaviors for the management and maintenance of health in people with stroke. These health behaviors, by their very nature, are also occupations; thus, they are influenced by client factors, performance skills and patterns, and environments and contexts. This article discusses physical activity and nutrition within the context of the Occupational Therapy Practice Framework: Domain and Process and proposes potential roles for occupational therapy practitioners and researchers in developing, testing, and providing physical activity and nutrition interventions for people with stroke.


Document Type: Article
Source: Scopus

 

6) 

Smallfield, S.
Supporting adults with Alzheimer's disease and related major neurocognitive disorders and their caregivers: Effective occupational therapy interventions
(2017) American Journal of Occupational Therapy, 71 (5), art. no. 7105170010, . 

DOI: 10.5014/ajot.2017.715002


Occupational Therapy and Medicine, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Occupational therapy practitioners play a significant role in supporting adults with Alzheimer's disease and related major neurocognitive disorders, as well as their caregivers, through all phases of the disease process. This editorial highlights the systematic reviews completed in collaboration with the American Occupational Therapy Association's Evidence-Based Practice Project that summarize the evidence for the effectiveness of interventions within the scope of occupational therapy practice for this population. Readers are encouraged to translate and integrate this updated knowledge into everyday practice.


Document Type: Review
Source: Scopus

 

7) 

Hirbe, A.C., Gutmann, D.H.
The management of neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors: challenges, progress, and future prospects
(2017) Expert Opinion on Orphan Drugs, 5 (8), pp. 623-631. 

DOI: 10.1080/21678707.2017.1348294


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


Abstract
Introduction: The most common malignancy affecting adults with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the malignant peripheral nerve sheath tumor (MPNST), a highly aggressive sarcoma that typically develops from a pre-existing benign plexiform neurofibroma. These tumors are difficult to treat, with limited therapeutic options and poor patient responses, leading to unacceptably high mortality rates. Despite advances in our understanding of the pathogenesis of these tumors, the overall prognosis for these cancers remains dismal. Areas covered: This paper reviews the cellular and molecular etiologies underlying MPNST development and progression, the diagnostic workup of patients with these malignancies, and the current and investigational treatment options. Areas of controversy in which further research is needed will be highlighted. Expert opinion: MPNSTs remain a therapeutic challenge. Multidisciplinary care at a high volume sarcoma center is essential for optimal outcomes. Further work is needed to develop targeted combinational therapies for these tumors. © 2017 Informa UK Limited, trading as Taylor & Francis Group.


Author Keywords
Atypical neurofibromas;  malignant peripheral nerve sheath tumors neurofibromatosis;  plexiform neurofibromas


Document Type: Review
Source: Scopus

 

8) 

Spolverato, G., Bagante, F., Aldrighetti, L., Poultsides, G., Bauer, T.W., Field, R.C., Marques, H.P., Weiss, M., Maithel, S.K., Pawlik, T.M.
Neuroendocrine Liver Metastasis: Prognostic Implications of Primary Tumor Site on Patients Undergoing Curative Intent Liver Surgery
(2017) Journal of Gastrointestinal Surgery, pp. 1-9. Article in Press. 

DOI: 10.1007/s11605-017-3491-1


a Department of Surgery, University of Verona, Verona, Italy
b Scientific Institute San Raffaele, Milan, Italy
c Stanford University, Stanford, CA, United States
d University of Virginia, Charlottesville, VA, United States
e School of Medicine, Washington University, St Louis, MO, United States
f Curry Cabral Hospital, Lisbon, Portugal
g Johns Hopkins Hospital, Baltimore, MD, United States
h Emory University, Atlanta, GA, United States
i Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States


Abstract
Background: Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on long-term prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the current study was to define the association of primary tumor location on prognosis of patients undergoing curative intent liver resection for NELM. Methods: Between 1990 and 2014, 421 patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified and analyzed by location of the primary tumor (PNET vs. non-PNET). A propensity score-matched analysis was utilized to assess the impact of primary tumor location on long-term survival. Results: Among the 421 patients, 197 (46.8%) patients had NELM from a PNET primary while 224 (53.2%) had a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22; other, n = 47). There were no differences in tumor burden and tumor site, while presence of extrahepatic disease was more common among patients with non-PNET NELM (extrahepatic disease, PNET NELM, n = 11 27.5% vs. non-PNET NELM, n = 29 72.5%; p = 0.010). Patients with PNET NELM were more likely to have non-functional disease compared with patients who had non-PNET NELM (non-functional, PNET NELM, n = 117 54.9% vs. non-PNET NELM, n = 96 45.1%; p = 0.011). On the final pathological specimen of the resected NELM, patients with PNET NELM were more likely to have a moderately differentiated tumor (59.3%), while patients with non-PNET NELM were more likely to have a poorly differentiated tumor (67.8%) (p = 0.005). Patients with PNET NELM had a worse 5-year DFS and 5-year OS compared with patients who had non-PNET NELM (DFS, PNET 36.2% vs. non-PNET 55.2%; p = 0.001 and OS, PNET 79.5% vs. non-PNET 83.4%; p = 0.008). After propensity score matching, both 5-year DFS and 5-year OS of the PNET and non-PNET groups were comparable (DFS, PNET 46.2% vs. non-PNET 55.9%; p = 0.22 and OS, PNET 81.5% vs. non-PNET 84.3%; p = 0.19). Conclusion: PNET patients more often present with non-functional NELM and moderately differentiated tumors. On propensity-matched analysis, factors such as extrahepatic disease and tumor grade, but not primary tumor location, were associated with prognosis of patients undergoing curative intent liver surgery for NELM. © 2017 The Society for Surgery of the Alimentary Tract


Author Keywords
NELM;  Neuroendocrine liver metastasis;  Pancreatic neuroendocrine tumor;  PNET;  Surgery


Document Type: Article in Press
Source: Scopus

 

9) 

Riggs, W.J., Roche, J.P., Giardina, C.K., Harris, M.S., Bastian, Z.J., Fontenot, T.E., Buchman, C.A., Brown, K.D., Adunka, O.F., Fitzpatrick, D.C.
Intraoperative electrocochleographic characteristics of auditory neuropathy spectrum disorder in cochlear implant subjects
(2017) Frontiers in Neuroscience, 11 (JUL), art. no. 416, . 

DOI: 10.3389/fnins.2017.00416


a Department of Otolaryngology/Head and Neck Surgery, Ohio State University College of Medicine, Columbus, OH, United States
b Lab Department of Otolaryngology/Head and Neck Surgery, University of Wisconsin School of Medicine, Madison, WI, United States
c Department of Otolaryngology/Head and Neck Surgery, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States
d Department of Otolaryngology/Head and Neck Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United States


Abstract
Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163). Magnitudes of the responses to tones of different frequencies were summed to measure the "total response" (ECochG-TR), a metric often dominated by hair cell activity, and auditory nerve activity was estimated visually from the compound action potential (CAP) and auditory nerve neurophonic (ANN) as a ranked "Nerve Score". Subjects identified as ANSD (45 ears in children, 3 in adults) had higher values of ECochG-TR than adult and pediatric subjects also receiving CIs not identified as ANSD. However, nerve scores of the ANSD group were similar to the other cohorts, although dominated by the ANN to low frequencies more than in the non-ANSD groups. To high frequencies, the common morphology of ANSD cases was a large CM and summating potential, and small or absent CAP. Common morphologies in other groups were either only a CM, or a combination of CM and CAP. These results indicate that responses to high frequencies, derived primarily from hair cells, are the main source of the CM used to evaluate ANSD in the clinical setting. However, the clinical tests do not capture the wide range of neural activity seen to low frequency sounds. © 2017 Riggs, Roche, Giardina, Harris, Bastian, Fontenot, Buchman, Brown, Adunka and Fitzpatrick.


Author Keywords
Auditory neuropathy spectrum disorder;  Cochlear implants;  Cochlear microphonic;  Electrocochleography;  Intraoperative;  Pediatrics


Document Type: Article
Source: Scopus

 

10) 

Barry, D.M., Yu, Y.-Q., Hao, Y., Liu, X.-T., Chen, Z.-F.
Response to comment on “Molecular and neural basis of contagious itch behavior in mice”
(2017) Science, 357 (6347), art. no. eaan5000, . 

DOI: 10.1126/science.aan5000


a Center for the Study of Itch, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Anesthesiology, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
d Department of Developmental Biology, Washington University, School of Medicine, St. Louis, MO, United States
e Institute for Biomedical Sciences of Pain, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
f Department of Pediatrics, Tongji Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan, Hubei, China
g Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China


Document Type: Note
Source: Scopus

 

11) 

Gendron, T.F., C9ORF72 Neurofilament Study Group, Daughrity, L.M., Heckman, M.G., Diehl, N.N., Wuu, J., Miller, T.M., Pastor, P., Trojanowski, J.Q., Grossman, M., Berry, J.D., Hu, W.T., Ratti, A., Benatar, M., Silani, V., Glass, J.D., Floeter, M.K., Jeromin, A., Boylan, K.B., Petrucelli, L.
Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis
(2017) Annals of Neurology, 82 (1), pp. 139-146. 

DOI: 10.1002/ana.24980


a Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
b Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL, United States
c Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, United States
d Department of Neurology, University of Miami, Miami, FL, United States
e Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
f Department of Neurology, University Hospital Mútua de Terrassa, and Research Foundation Mútua de Terrassa, University of Barcelona, Terrassa, Barcelona, Spain
g Centers for Networked Biomedical Research (CIBERNED), Madrid, Spain
h Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
i Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, PA, United States
j Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA, United States
k Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
l Department of Neurology–Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy
m Department of Pathophysiology and Transplantation, “Dino Ferrari” Centre, University of Milan, Milan, Italy
n Department of Pathology, Emory University School of Medicine, Atlanta, GA, United States
o Motor Neuron Disorders Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
p Iron Horse Diagnostics, Scottsdale, AZ, United States
q Department of Neurology, Mayo Clinic, Jacksonville, FL, United States


Abstract
As potential treatments for C9ORF72-associated amyotrophic lateral sclerosis (c9ALS) approach clinical trials, the identification of prognostic biomarkers for c9ALS becomes a priority. We show that levels of phosphorylated neurofilament heavy chain (pNFH) in cerebrospinal fluid (CSF) predict disease status and survival in c9ALS patients, and are largely stable over time. Moreover, c9ALS patients exhibit higher pNFH levels, more rapid disease progression, and shorter survival after disease onset than ALS patients without C9ORF72 expansions. These data support the use of CSF pNFH as a prognostic biomarker for clinical trials, which will increase the likelihood of successfully developing a treatment for c9ALS. Ann Neurol 2017;82:139–146. © 2017 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association


Document Type: Article
Source: Scopus

 

12) 

Santosa, K.B., Fattah, A., Gavilán, J., Hadlock, T.A., Snyder-Warwick, A.K.
Photographic standards for patients with facial palsy and recommendations by members of the sir charles bell society
(2017) JAMA Facial Plastic Surgery, 19 (4), pp. 275-281. 

DOI: 10.1001/jamafacial.2016.1883


a Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO, United States
b Facial Nerve Programme, Regional Paediatric Burns and Plastic Surgery Service, Alder Hey Children's National Health Service Foundation Trust, Liverpool, United Kingdom
c Department of Otorhinolaryngology, La Paz University Hospital, Madrid, Spain
d Facial Nerve Center, Division of Facial and Plastic and Reconstructive Surgery, Department of Otology and Laryngology, Harvard Medical School and Massachusetts Eye and Ear, Boston, United States
e Facial Nerve Institute, Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8238, St Louis, MO, United States


Abstract
IMPORTANCE There is no widely accepted assessment tool or common language used by clinicians caring for patients with facial palsy, making exchange of information challenging. Standardized photographymay represent such a language and is imperative for precise exchange of information and comparison of outcomes in this special patient population. OBJECTIVES To review the literature to evaluate the use of facial photography in the management of patients with facial palsy and to examine the use of photography in documenting facial nerve function among members of the Sir Charles Bell Society-a group of medical professionals dedicated to care of patients with facial palsy. DESIGN, SETTING, AND PARTICIPANTS A literature searchwas performed to review photographic standards in patients with facial palsy. In addition, a cross-sectional survey of members of the Sir Charles Bell Society was conducted to examine use of medical photography in documenting facial nerve function. The literature search and analysis was performed in August and September 2015, and the survey was conducted in August and September 2013. MAIN OUTCOMES AND MEASURES The literature review searched EMBASE, CINAHL, and MEDLINE databases from inception of each database through September 2015. Additional studieswere identified by scanning references from relevant studies. Only English-language articleswere eligible for inclusion. Articles that discussed patients with facial palsy and outlined photographic guidelines for this patient populationwere included in the study. The surveywas disseminated to the Sir Charles Bell Society members in electronic form. It consisted of 10 questions related to facial grading scales, patient-reported outcome measures, other psychological assessment tools, and photographic and videographic recordings. RESULTS In total, 393 articles were identified in the literature search, 7 of which fit the inclusion criteria. Six of the 7 articles discussed or proposed views specific to patients with facial palsy. However, none of the articles specifically focused on photographic standards for the population with facial palsy. Eighty-three of 151 members (55%) of the Sir Charles Bell Society responded to the survey. All survey respondents used photographic documentation, but there was variability in which facial expressions were used. Eighty-two percent (68 of 83) used some form of videography. From these data, we propose a set of minimum photographic standards for patients with facial palsy, including the following 10 static views: at rest or repose, small closed-mouth smile, large smile showing teeth, elevation of eyebrows, closure of eyes gently, closure of eyes tightly, puckering of lips, showing bottom teeth, snarling or wrinkling of the nose, and nasal base view. CONCLUSIONS AND RELEVANCE There is no consensus on photographic standardization to report outcomes for patients with facial palsy. Minimum photographic standards for facial paralysis publications are proposed. Videography of the dynamic movements of these views should also be recorded. © 2017 American Medical Association. All rights reserved.


Document Type: Review
Source: Scopus

 

13) 

Zhang, D.J., Allon, G., Van Mieghem, J.A.
Does social interaction improve learning outcomes? Evidence from field experiments on massive open online courses
(2017) Manufacturing and Service Operations Management, 19 (3), pp. 347-367. 

DOI: 10.1287/msom.2016.0615


a Olin Business School, Washington University in St. Louis, St. Louis, MO, United States
b Wharton School, University of Pennsylvania, Philadelphia, PA, United States
c Kellogg School of Management, Northwestern University, Evanston, IL, United States


Abstract
This paper studies how service providers can design social interaction among participants and quantify the causal impact of that interaction on service quality. We focus on education and analyze whether encouraging social interaction among students improves learning outcomes in massive open online courses (MOOCs), which are a new service delivery channel with universal access at reduced, if not zero, cost. We analyze three randomized experiments in a MOOC with more than 30,317 students from 183 countries. Two experiments study large-group interaction by encouraging a random subset of students to visit the course discussion board. The majority of students treated in these experiments had higher social engagement, higher quiz completion rates, and higher course grades. Using these treatments as instrumental variables, we estimate that one additional board visit causally increases the probability that a student finishes the quiz in the subsequent week by up to 4:3%. The third experiment studies small-group interaction by encouraging a random subset of students to conduct one-onone synchronous discussions. Students who followed through and actually conducted pairwise discussions increased their quiz completion rates and quiz scores by 10% in the subsequent week. Combining results from these three experiments, we provide recommendations for designing social interaction mechanisms to improve service quality. © 2017 INFORMS.


Author Keywords
Education;  Field experiments;  Massive open online courses (MOOCs);  Service operations;  Social interaction


Document Type: Article
Source: Scopus

 

14) 

Su, Y., Vlassenko, A.G., Couture, L.E., Benzinger, T.L., Snyder, A.Z., Derdeyn, C.P., Raichle, M.E.
Quantitative hemodynamic PET imaging using image-derived arterial input function and a PET/MR hybrid scanner
(2017) Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 37 (4), pp. 1435-1446. Cited 1 time.

DOI: 10.1177/0271678X16656200


a 1 Mallinckrodt Institute of Radiology, Washington University School of Medicine, USA
b 2 Department Neurosurgery, Washington University School of Medicine, USA
c 3 Department of Radiology, University of Iowa, USA
d 4 Department of Neurology, Washington University School of Medicine, USA


Abstract
Positron emission tomography (PET) with 15O-tracers is commonly used to measure brain hemodynamic parameters such as cerebral blood flow, cerebral blood volume, and cerebral metabolic rate of oxygen. Conventionally, the absolute quantification of these parameters requires an arterial input function that is obtained invasively by sampling blood from an artery. In this work, we developed and validated an image-derived arterial input function technique that avoids the unreliable and burdensome arterial sampling procedure for full quantitative 15O-PET imaging. We then compared hemodynamic PET imaging performed on a PET/MR hybrid scanner against a conventional PET only scanner. We demonstrated the proposed imaging-based technique was able to generate brain hemodynamic parameter measurements in strong agreement with the traditional arterial sampling based approach. We also demonstrated that quantitative 15O-PET imaging can be successfully implemented on a PET/MR hybrid scanner.


Author Keywords
Arterial input function;  cerebral blood flow;  cerebral metabolic rate of oxygen;  positron emission tomography


Document Type: Article
Source: Scopus

 

15) 

Cicero, T.J., Ellis, M.S.
Understanding the demand side of the prescription opioid epidemic: Does the initial source of opioids matter?
(2017) Drug and Alcohol Dependence, 173, pp. S4-S10. 

DOI: 10.1016/j.drugalcdep.2016.03.014


Washington University in St. Louis, Department of Psychiatry, Campus Box 8134, 660 S. Euclid Avenue, St. Louis, MO, United States


Abstract
Background These studies were carried out to examine whether the onset and progression of an opioid substance use disorder (SUD) differed in those who first used opioids to get “high” compared to those who received a prescription from a doctor to relieve pain (Non-Rx vs. Rx groups, respectively). Methods A subset of patients (N = 214) from an ongoing larger study of patients entering one of 125 drug treatment programs for opioid use disorder across the country agreed to give up their anonymity and participate in structured and open-ended online interviews examining drug abuse patterns. Results With the exception that the Non-Rx group began their opioid abuse at a younger age than the Rx group and more quickly evolved from initial exposure to regular opioid abuse, there were relatively few differences in the characteristics, patterns and trajectories of opioid abuse. The vast majority of patients in both groups, most of whom had serious, antecedent psychiatric disorders, indicated that they used opioids to self-medicate psychological problems (67–73%) and/or stated that opioids provided a means to “escape” from the stresses of everyday life (79–85%). As the SUD progressed, for many individuals any “positive” attributes of opioids waned and avoidance of withdrawal became the overriding concern, often serving as the impetus for treatment. Conclusions Our results suggest that self-treatment of co-morbid psychiatric disturbances is a powerful motivating force to initiate and sustain abuse of opioids and that the initial source of drugs—a prescription or experimentation—is largely irrelevant in the progression to a SUD. © 2016 The Authors


Author Keywords
Epidemiology;  Iatrogenic abuse;  Opioid abuse;  Opioids;  Pharmacoepidemiology;  Psychiatric epidemiology


Document Type: Article
Source: Scopus

 

16) 

Yi, J.J., Paranjape, S.R., Walker, M.P., Choudhury, R., Wolter, J.M., Fragola, G., Emanuele, M.J., Major, M.B., Zylka, M.J.
The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/β-catenin pathway by inhibiting the proteasome
(2017) Journal of Biological Chemistry, 292 (30), pp. 12503-12515. 

DOI: 10.1074/jbc.M117.788448


a Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, United States
c UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, United States
d Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, United States
e Department of Pharmacology, University of North Carolina, Chapel Hill, NC, United States
f Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States


Abstract
UBE3A is a HECT domain E3 ubiquitin ligase whose dysfunction is linked to autism, Angelman syndrome, and cancer. Recently, we characterized a de novo autism-linked UBE3A mutant (UBE3AT485A) that disrupts phosphorylation control of UBE3A activity. Through quantitative proteomics and reporter assays, we found that the UBE3AT485A protein ubiquitinates multiple proteasome subunits, reduces proteasome subunit abundance and activity, stabilizes nuclear β-catenin, and stimulates canonical Wnt signaling more effectively than wild-type UBE3A. We also found that UBE3AT485A activates Wnt signaling to a greater extent in cells with low levels of ongoing Wnt signaling, suggesting that cells with low basal Wnt activity are particularly vulnerable to UBE3AT485A mutation. Ligase-dead UBE3A did not stimulate Wnt pathway activation. Overexpression of several proteasome subunits reversed the effect of UBE3AT485A on Wnt signaling. We also observed that subunits that interact with UBE3A and affect Wnt signaling are located along one side of the 19S regulatory particle, indicating a previously unrecognized spatial organization to the proteasome. Altogether, our findings indicate that UBE3A regulates Wnt signaling in a cell context-dependent manner and that an autism-linked mutation exacerbates these signaling effects. Our study has broad implications for human disorders associated with UBE3A gain or loss of function and suggests that dysfunctional UBE3A might affect additional proteins and pathways that are sensitive to proteasome activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.


Document Type: Article
Source: Scopus

 

17) 

Couture, F., Jansen, A.M., Taghert, P., Brix, K.
EJCB - Molecular basis of protein fates in the secretory and endocytic pathways, and beyond
(2017) European Journal of Cell Biology, . Article in Press. 

DOI: 10.1016/j.ejcb.2017.06.006


a University of Sherbrooke, 3001, 12e avenue Nord, Sherbrooke, Québec, J1H 5N4, Canada
b Kongshaven 22B, 2500 Valby, Denmark
c Washington University Medical School, 660 S Euclid Avenue, St Louis MO 63110, USA
d Jacobs University Bremen gGmbH, Campus Ring 1, 28759 Bremen, Germany


Document Type: Article in Press
Source: Scopus

 

18) 

Gordon, E.M., Laumann, T.O., Gilmore, A.W., Newbold, D.J., Greene, D.J., Berg, J.J., Ortega, M., Hoyt-Drazen, C., Gratton, C., Sun, H., Hampton, J.M., Coalson, R.S., Nguyen, A.L., McDermott, K.B., Shimony, J.S., Snyder, A.Z., Schlaggar, B.L., Petersen, S.E., Nelson, S.M., Dosenbach, N.U.F.
Precision Functional Mapping of Individual Human Brains
(2017) Neuron, . Article in Press. 

DOI: 10.1016/j.neuron.2017.07.011


a VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, 76711, USA
b Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, 75235, USA
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110, USA
d Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA
e Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA
f Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA
g Department of Psychology, New York University, New York, NY 10003, USA
h Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, 63110, USA
i Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, 63130, USA
j Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, 63110, USA
k Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, 63110, USA
l Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA
m Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA
n Department of Psychology and Neuroscience, Baylor University, Waco, TX 76789, USA


Abstract
Human functional MRI (fMRI) research primarily focuses on analyzing data averaged across groups, which limits the detail, specificity, and clinical utility of fMRI resting-state functional connectivity (RSFC) and task-activation maps. To push our understanding of functional brain organization to the level of individual humans, we assembled a novel MRI dataset containing 5 hr of RSFC data, 6 hr of task fMRI, multiple structural MRIs, and neuropsychological tests from each of ten adults. Using these data, we generated ten high-fidelity, individual-specific functional connectomes. This individual-connectome approach revealed several new types of spatial and organizational variability in brain networks, including unique network features and topologies that corresponded with structural and task-derived brain features. We are releasing this highly sampled, individual-focused dataset as a resource for neuroscientists, and we propose precision individual connectomics as a model for future work examining the organization of healthy and diseased individual human brains. Gordon et al. demonstrate advantages of conducting whole-brain fMRI research in individual humans using large amounts of per-individual data, which greatly increases reliability and specificity. This work illustrates new approaches for fMRI-based neuroscience that allow detailed characterization of individual brain organization. © 2017 Elsevier Inc.


Author Keywords
Brain networks;  FMRI;  Functional connectivity;  Individual variability;  Myelin mapping


Document Type: Article in Press
Source: Scopus

 

19) 

TCW, J., Wang, M., Pimenova, A.A., Bowles, K.R., Hartley, B.J., Lacin, E., Machlovi, S.I., Abdelaal, R., Karch, C.M., Phatnani, H., Slesinger, P.A., Zhang, B., Goate, A.M., Brennand, K.J.
An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells
(2017) Stem Cell Reports, . Article in Press. 

DOI: 10.1016/j.stemcr.2017.06.018


a Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA
b Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA
c Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA
d Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA
e New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA
f Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA


Abstract
Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. Brennand, Goate, and colleagues report a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs) via a neural progenitor cell (NPC) intermediate. hiPSC-astrocytes resemble primary human fetal astrocytes, have a transcriptional signature consistent with a non-reactive state, respond to inflammatory stimulants, and enhance microglial phagocytosis. © 2017 The Author(s).


Author Keywords
Astrocyte;  Human induced pluripotent stem cell;  IPSC


Document Type: Article in Press
Source: Scopus

 

20) 

Agrawal, A., Nelson, E.C., Bucholz, K.K., Tillman, R., Grucza, R.A., Statham, D.J., Madden, P.A.F., Martin, N.G., Heath, A.C., Lynskey, M.T.
Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: A retrospective cohort study
(2017) The Lancet Psychiatry, . Article in Press. 

DOI: 10.1016/S2215-0366(17)30280-8


a Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
b QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
c University of the Sunshine Coast, Sippy Downs, QLD, Australia
d National Addictions Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK


Abstract
Background: Early and frequent cannabis use are associated with an increased likelihood of major depressive disorder (MDD) as well as suicidal thoughts and behaviours. We identify associations between aspects of cannabis use, MDD, and suicidal thoughts and behaviours and examine whether such associations persist after accounting for those predisposing factors, including genetic liability and early family environment, that are shared by identical twins who are discordant for cannabis exposure. Any residual association in such identical pairs might be indicative of individual-specific pathways that might be of a causal nature. Methods: We did a logistic regression analysis of cannabis use from retrospective data on same-sex male and female twin pairs drawn from 3 studies that had recruited twins from the Australian Twin Registry, 1992-93 (sample 1), 1996-2000 (sample 2), and 2005-09 (sample 3). We studied associations between early use and frequent use of cannabis and MDD, suicidal ideation (ever and persistent), and suicide plan and attempt in the full sample as well as in pairs of monozygotic and dizygotic twins that were discordant for each measure of cannabis involvement at a single timepoint. Significant monozygotic associations were further adjusted for covariates, such as early alcohol or nicotine use, early dysphoric or anhedonic mood, conduct disorder, and childhood sexual abuse. Interactions between each cannabis measure and sex, sample or study effects, and birth year category were also examined as covariates. Findings: In 13 986 twins (6181 monozygotic and 7805 dizygotic), cannabis use ranged from 1345 (30·4%) of 4432 people in sample 1 to 2275 (69·0%) of 3299 in sample 3. Mean age of first cannabis use ranged from 17·9 years (SD 3·3) in sample 3 to 21·1 years (5·2) in sample 1, and frequent use (≥100 times) was reported by 214 (15·9%) of 1345 users in sample 1 and 499 (21·9%) of 2275 in sample 3. The prevalence of suicidal ideation ranged from 1102 (24·9%) of 4432 people in sample 1 to 1644 (26·3%) of 6255 people in sample 2 and 865 (26·2%) of 3299 people in sample 3. Prevalence of MDD ranged from 901 (20·3%) people in sample 1 to 1773 (28·3%) in sample 2. The monozygotic twin who used cannabis frequently was more likely to report MDD (odds ratio 1·98, 95% CI 1·11-3·53) and suicidal ideation (2·47, 1·19-5·10) compared with their identical twin who had used cannabis less frequently, even after adjustment for covariates. For early cannabis use, the monozygotic point estimate was not significant but could be equated to the significant dizygotic estimate, suggesting a possible association with suicidal ideation. Interpretation: The increased likelihood of MDD and suicidal ideation in frequent cannabis users cannot be solely attributed to common predisposing factors. Funding: National Institute on Drug Abuse, National Institutes of Health, Australian National Health and Medical Research Council. © 2017 Elsevier Ltd.


Document Type: Article in Press
Source: Scopus

 

21) 

Chitnis, T., Graves, J., Weinstock-Guttman, B., Belman, A., Olsen, C., Misra, M., Aaen, G., Benson, L., Candee, M., Gorman, M., Greenberg, B., Krupp, L., Lotze, T., Mar, S., Ness, J., Rose, J., Rubin, J., Schreiner, T., Tillema, J., Waldman, A., Rodriguez, M., Casper, C., Waubant, E.
Distinct effects of obesity and puberty on risk and age at onset of pediatric MS
(2016) Annals of Clinical and Translational Neurology, 3 (12), pp. 897-907. 

DOI: 10.1002/acn3.365


a Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital for Children, Boston, MA, United States
b Department of Neurology, University of California, San Francisco, CA, United States
c Pediatric Multiple Sclerosis Center, Jacobs Neurological Institute, SUNY Buffalo, NY, United States
d Lourie Center for Pediatric MS, Stony Brook Children's Hospital, Stonybrook, NY, United States
e Department of Pediatrics, University of Utah, Salt Lake City, UT, United States
f Department of Pediatric Endocrinology, Massachusetts General Hospital for Children, Boston, MA, United States
g Pediatric MS Center at Loma Linda University Children's Hospital, Loma Linda, CA, United States
h Boston Children's Hospital, Boston, MA, United States
i University of Utah/Primary Children's Hospital, Salt Lake City, UT, United States
j Department of Neurology, UT Southwestern, Dallas, TX, United States
k Blue Bird Circle Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX, United States
l Pediatric Onset Demyelinating Diseases and Autoimmune Encephalitis Center, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO, United States
m University of Alabama Center for Pediatric Onset Demyelinating Disease, Children's Hospital of Alabama, Birmingham, AL, United States
n Department of Neurology, University of Utah, Salt Lake City, UT, United States
o Department of Pediatric Neurology, Northwestern Feinberg School of Medicine, Chicago, IL, United States
p Children's Hospital Colorado, University of Colorado, Denver, CO, United States
q Mayo Clinic's Pediatric MS Center, Rochester, MN, United States
r Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States
s Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, CA, United States


Abstract
Objective: The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS. Methods: Case–control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex- and age-stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex-stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity. Results: Only 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001). Interpretation: Higher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity. © 2016 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.


Document Type: Article
Source: Scopus