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

WUSTL Neuroscience Publications Archive - June 2017

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June 26, 2017

June 19, 2017

June 12, 2017

June 5, 2017

 

June 26, 2017

1) 

Guo, D., Zou, J., Wong, M.
Rapamycin attenuates acute seizure-induced astrocyte injury in mice in vivo
(2017) Scientific Reports, 7 (1), art. no. 2867, . 

DOI: 10.1038/s41598-017-03032-0


Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Astrocytes have been implicated in epileptogenesis and seizure-induced brain injury. Pathological studies reveal a variety of structural abnormalities in astrocytes, such as vacuolization and astrogliosis. While in vivo imaging methods have demonstrated rapid changes in astrocytes under a variety of physiological and pathological conditions, the acute effects of seizures on astrocyte morphology in vivo and corresponding mechanisms of seizure-induced astrocytic injury have not been documented. In this study, we utilized in vivo two-photon imaging to directly monitor the acute structural effects of kainate-induced seizures on cortical astrocytes. Kainate seizures cause an immediate, but transient, vacuolization of astrocytes, followed over several days by astrogliosis. These effects are prevented by pre- or post-treatment with rapamycin, indicating the mTOR pathway is involved in mediating seizureinduced astrocyte injury. These finding have clinical implications for mechanisms of seizure-induced astrocyte injury and potential therapeutic applications with mTOR inhibitors. © The Author(s) 2017.


Document Type: Article
Source: Scopus


2) 

Lin, C.-C., Edelson, B.T.
New insights into the role of IL-1b in experimental autoimmune encephalomyelitis and multiple sclerosis
(2017) Journal of Immunology, 198 (12), pp. 4553-4560. 

DOI: 10.4049/jimmunol.1700263


Department of Pathology and Immunology, Washington University School of Medicine, Division of Laboratory and Genomic Medicine, Box 8118, St. Louis, MO, United States


Abstract
Multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis, are neuroinflammatory diseases driven by autoreactive pathogenic TH cells that elicit demyelination and axonal damage. How TH cells acquire pathogenicity and communicate with myeloid cells and cells of the CNS remain unclear. IL-1β is recognized to play an important role in experimental autoimmune encephalomyelitis (EAE) and perhaps MS. Clinical EAE is significantly attenuated in IL-1R-deficient and IL-1β-deficient mice, and IL-1β is found in the blood, cerebrospinal fluid, and CNS lesions of MS patients. In this article, we focus on new reports that elucidate the cellular sources of IL-1β and its actions during EAE, in both lymphoid tissues and within the CNS. Several immune cell types serve as critical producers of IL-1β during EAE, with this cytokine inducing response in both hematopoietic and nonhematopoietic cells. These findings from the EAE model should inspire efforts toward investigating the therapeutic potential of IL-1 blockade in MS. Copyright © 2017 by The American Association of Immunologists, Inc.


Document Type: Review
Source: Scopus


3) 

Miner, J.J.
Congenital Zika virus infection: More than just microcephaly
(2017) Science Translational Medicine, 9 (393), art. no. eaan8195, . 

DOI: 10.1126/scitranslmed.aan8195


Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States


Abstract
A nonhuman primate model demonstrates efficient vertical transmission of Zika virus. © 2017, American Association for the Advancement of Science.


Document Type: Review
Source: Scopus


4) 

Emerson, R.W.a , Adams, C.b , Nishino, T.b , Hazlett, H.C.a c , Wolff, J.J.d , Zwaigenbaum, L.e , Constantino, J.N.b , Shen, M.D.a , Swanson, M.R.a , Elison, J.T.f , Kandala, S.b , Estes, A.M.g , Botteron, K.N.b h , Collins, L.i , Dager, S.R.j k , Evans, A.C.i , Gerig, G.l , Gu, H.a , Mckinstry, R.C.h , Paterson, S.m , Schultz, R.T.m , Styner, M.a , Schlaggar, B.L.b h n , Pruett, J.R., Jr.b , Piven, J.a c 
Functional neuroimaging of high-risk 6-month-old infants predicts a diagnosis of autism at 24 months of age
(2017) Science Translational Medicine, 9 (393), art. no. eaag2882, . 

DOI: 10.1126/scitranslmed.aag2882


a Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
d Department of Educational Psychology, University of Minnesota, Minneapolis, MN, United States
e Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
f Institute of Child Development, University of Minnesota, Minneapolis, MN, United States
g Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, United States
h Mallinckrodt Institute of Radiology, Washington University School OfMedicine, Washington University, St. Louis, MO, United States
i Montreal Neurological Institute, McGill University, Montreal, QC, Canada
j Center on Human Development and Disability, University of Washington, Seattle, WA, United States
k Department of Radiology, University of Washington, Seattle, WA, United States
l Tandon School of Engineering, New York University, Brooklyn, NY, United States
m Center for Autism Research, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, PA, United States
n Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors that typically emerge by 24 months of age. To develop effective early interventions that can potentially ameliorate the defining deficits of ASD and improve long-Term outcomes, early detection is essential. Using prospective neuroimaging of 59 6-month-old infants with a high familial risk for ASD, we show that functional connectivity magnetic resonance imaging correctly identified which individual children would receive a research clinical best-estimate diagnosis of ASD at 24months of age. Functional brain connections were defined in 6-month-old infants that correlated with 24-month scores on measures of social behavior, language, motor development, and repetitive behavior, which are all features common to the diagnosis of ASD. A fully cross-validated machine learning algorithm applied at age 6 months had a positive predictive value of 100% [95% confidence interval (CI), 62.9 to 100], correctly predicting 9 of 11 infants who received a diagnosis of ASD at 24 months (sensitivity, 81.8%; 95% CI, 47.8 to 96.8). All 48 6-month-old infants who were not diagnosed with ASD were correctly classified [specificity, 100% (95% CI, 90.8 to 100); negative predictive value, 96.0% (95% CI, 85.1 to 99.3)]. These findings have clinical implications for early risk assessment and the feasibility of developing early preventative interventions for ASD. © 2017, The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.


Document Type: Article
Source: Scopus


5) 

Xia, L.a d , Nygard, S.K.a b , Sobczak, G.G.a , Hourguettes, N.J.a , Bruchas, M.R.a b c d e 
Dorsal-CA1 Hippocampal Neuronal Ensembles Encode Nicotine-Reward Contextual Associations
(2017) Cell Reports, 19 (10), pp. 2143-2156. 

DOI: 10.1016/j.celrep.2017.05.047


a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States
d Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
e Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Natural and drug rewards increase the motivational valence of stimuli in the environment that, through Pavlovian learning mechanisms, become conditioned stimuli that directly motivate behavior in the absence of the original unconditioned stimulus. While the hippocampus has received extensive attention for its role in learning and memory processes, less is known regarding its role in drug-reward associations. We used in vivo Ca2+ imaging in freely moving mice during the formation of nicotine preference behavior to examine the role of the dorsal-CA1 region of the hippocampus in encoding contextual reward-seeking behavior. We show the development of specific neuronal ensembles whose activity encodes nicotine-reward contextual memories and that are necessary for the expression of place preference. Our findings increase our understanding of CA1 hippocampal function in general and as it relates to reward processing by identifying a critical role for CA1 neuronal ensembles in nicotine place preference. © 2017 The Authors


Author Keywords
dorsal CA1 hippocampus;  in vivo calcium imaging;  nicotine;  place preference


Document Type: Article
Source: Scopus


6) 

Ashton, N.J.a b , Hye, A.a b , Leckey, C.A.a b , Jones, A.R.a , Gardner, A.c , Elliott, C.a , Wetherell, J.L.d e , Lenze, E.J.f , Killick, R.a , Marchant, N.L.a c 
Plasma REST: A novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population
(2017) Translational Psychiatry, 7 (6), art. no. e1148, . 

DOI: 10.1038/tp.2017.113


a Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, King's College London, London, United Kingdom
b NIHR Biomedical Research Centre for Mental Health, Biomedical Research Unit for Dementia, South London and Maudsley NHS Foundation, London, United Kingdom
c Division of Psychiatry, University College London, 6th Floor Maple House, 149 Tottenham Court Road, London, United Kingdom
d VA San Diego Healthcare System, University of California, San Diego, San Diego, CA, United States
e Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
f Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: Healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit. © 2017 The Author(s).


Document Type: Article
Source: Scopus


7) 

Dhavale, D.D., Tsai, C., Bagchi, D.P., Engel, L.A., Sarezky, J., Kotzbauer, P.T.
A sensitive assay reveals structural requirements for α-synuclein fibril growth
(2017) Journal of Biological Chemistry, 292 (22), pp. 9034-9050. 

DOI: 10.1074/jbc.M116.767053


Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The accumulation of α-synuclein (α-syn) fibrils in neuronal inclusions is the defining pathological process in Parkinson's disease (PD). A pathogenic role for α-syn fibril accumulation is supported by the identification of dominantly inherited α-syn (SNCA) gene mutations in rare cases of familial PD. Fibril formation involves a spontaneous nucleation event in which soluble α-syn monomers associate to form seeds, followed by fibril growth during which monomeric α-syn molecules sequentially associate with existing seeds. To better investigate this process, we developed sensitive assays that use the fluorescein arsenical dye FlAsH (fluorescein arsenical hairpin binder) to detect soluble oligomers and mature fibrils formed from recombinant α-syn protein containing an N-terminal bicysteine tag (C2-α-syn). Using seed growth by monomer association (SeGMA) assays to measure fibril growth over 3 h in the presence of C2-α-syn monomer, we observed that some familial PD-associated α-syn mutations (i.e. H50Q and A53T) greatly increased growth rates, whereas others (E46K, A30P, and G51D) decreased growth rates. Experiments with wild-type seeds extended by mutant monomer and vice versa revealed that single-amino acid differences between seed and monomer proteins consistently decreased growth rates. These results demonstrate that α-syn monomer association during fibril growth is a highly ordered process that can be disrupted by misalignment of individual amino acids and that only a subset of familial-PD mutations causes fibril accumulation through increased fibril growth rates. The SeGMA assays reported herein can be utilized to further elucidate structural requirements of α-syn fibril growth and to identify growth inhibitors as a potential therapeutic approach in PD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.


Document Type: Article
Source: Scopus


8) 

Budelier, M.M.a b , Cheng, W.W.L.a , Bergdoll, L.f , Chen, Z.-W.a e , Janetka, J.W.b , Abramson, J.f h , Krishnan, K.e , Mydock-McGrane, L.c e , Covey, D.F.a c d e , Whitelegge, J.P.g , Evers, A.S.a c 
Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1
(2017) Journal of Biological Chemistry, 292 (22), pp. 9294-9304. 

DOI: 10.1074/jbc.M116.773069


a Dept. of Anesthesiology, Washington University School of Medicine, Campus Box 8054, St. Louis, MO, United States
b Departments of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO, United States
c Departments of Developmental Biology, Washington University in St. Louis, St. Louis, MO, United States
d Departments of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
e Taylor Family Institute for Innovative Psychiatric Research, Washington University in St. Louis, St. Louis, MO, United States
f Departments of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
g Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
h Institute for Stem Cell Biology and Regenerative Medicine, Nation Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, India


Abstract
Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both topdown mass spectrometry (MS), and bottom-upMSpaired with a clickable, stable isotope-labeled tag, FLI-tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr83 and Glu73, respectively. When Glu73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu73 residue. © 2017 by The American Society for Biochemistry and Molecular.


Document Type: Article
Source: Scopus

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9) 

Dresner, S.M.a , Kung, N.H.b , Palko, J.R.b , McJunkin, J.L.c , Goebel, J.A.c , Van Stavern, G.P.b 
Skew Deviation and Partial Ocular Tilt Reaction Due to Intratympanic Gentamicin Injection, with Review of the Literature
(2017) Neuro-Ophthalmology, pp. 1-3. Article in Press. 

DOI: 10.1080/01658107.2017.1296469


a New York Medical College, Valhalla, New York, USA
b Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, Missouri, USA
c Department of Otolaryngology—Head and Neck Surgery, Washington University in St. Louis, St. Louis, Missouri, USA


Abstract
Skew deviation is a rare side effect of intratympanic gentamicin injection for intractable Meniere’s disease. When the skew deviation is accompanied by pathologic head tilt and ocular torsion, the result is an ocular tilt reaction (OTR). The authors report the case of a 56-year-old man with refractory Meniere’s disease who developed binocular vertical diplopia following intratympanic gentamicin injection and was found to have skew deviation and a partial ocular tilt reaction. The authors also review the reported cases of skew deviation following intratympanic gentamicin and confirm this phenomenon, which has only rarely been reported in the literature. © 2017 Taylor & Francis


Author Keywords
Gentamicin;  ocular tilt reaction;  skew deviation


Document Type: Article in Press
Source: Scopus


10) 

Arnold, K.M.a , Umanath, S.b , Thio, K.c , Reilly, W.B.d , McDaniel, M.A.e , Marsh, E.J.a 
Understanding the cognitive processes involved in writing to learn
(2017) Journal of Experimental Psychology: Applied, 23 (2), pp. 115-127. 

DOI: 10.1037/xap0000119


a Department of Psychology and Neuroscience, Duke University, United States
b Department of Psychology, Claremont McKenna College, United States
c Office of Research Support, Duke University, United States
d Center for Neuroscience, Department of Psychology, University of California at Davis, United States
e Department of Psychological and Brain Sciences, Washington University in St. Louis, United States


Abstract
Writing is often used as a tool for learning. However, empirical support for the benefits of writing-tolearn is mixed, likely because the literature conflates diverse activities (e.g., summaries, term papers) under the single umbrella of writing-to-learn. Following recent trends in the writing-to-learn literature, the authors focus on the underlying cognitive processes. They draw on the largely independent writingto- learn and cognitive psychology learning literatures to identify important cognitive processes. The current experiment examines learning from 3 writing tasks (and 1 nonwriting control), with an emphasis on whether or not the tasks engaged retrieval. Tasks that engaged retrieval (essay writing and free recall) led to better final test performance than those that did not (note taking and highlighting). Individual differences in structure building (the ability to construct mental representations of narratives; Gernsbacher, Varner, & Faust, 1990) modified this effect; skilled structure builders benefited more from essay writing and free recall than did less skilled structure builders. Further, more essay-like responses led to better performance, implicating the importance of additional cognitive processes such as reorganization and elaboration. The results highlight how both task instructions and individual differences affect the cognitive processes involved when writing-to-learn, with consequences for the effectiveness of the learning strategy. © 2017 American Psychological Association.


Author Keywords
Cognitive processes;  Essays;  Individual differences;  Retrieval;  Writing-to-learn


Document Type: Article
Source: Scopus


11) 

Greenberg, J.K.a , Guniganti, R.a , Arias, E.J.a , Desai, K.a , Washington, C.W.a , Yan, Y.b , Weng, H.c , Xiong, C.c , Fondahn, E.d , Cross, D.T.a e , Moran, C.J.a e , Rich, K.M.a , Chicoine, M.R.a , Dhar, R.f , Dacey, R.G., Jr.a , Derdeyn, C.P.a e f g , Zipfel, G.J.a c f 
Predictors of 30-day readmission after aneurysmal subarachnoid hemorrhage: A case-control study
(2017) Journal of Neurosurgery, 126 (6), pp. 1847-1854. 

DOI: 10.3171/2016.5.JNS152644


a Departments of Neurological Surgery, India
b Departments of Surgery, India
c Department of Neurosurgery, School of Medicine in St. Louis, Washington University, 660 S Euclid Ave., St. Louis, MO, United States
d Departments of Medicine, United States
e Mallinckrodt Institute of Radiology, United States
f Departments of Neurology, United States
g Departments of Radiology Neurology, and Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States


Abstract
OBJECTIVE Despite persisting questions regarding its appropriateness, 30-day readmission is an increasingly common quality metric used to influence hospital compensation in the United States. However, there is currently insufficient evidence to identify which patients are at highest risk for readmission after aneurysmal subarachnoid hemorrhage (SAH). The objective of this study was to identify predictors of 30-day readmission after SAH, to focus preventative efforts, and to provide guidance to funding agencies seeking to risk-Adjust comparisons among hospitals. METHODS The authors performed a case-control study of 30-day readmission among aneurysmal SAH patients treated at a single center between 2003 and 2013. To control for geographic distance from the hospital and year of treatment, the authors randomly matched each case (30-day readmission) with approximately 2 SAH controls (no readmission) based on home ZIP code and treatment year. They evaluated variables related to patient demographics, socioeconomic characteristics, comorbidities, presentation severity (e.g., Hunt and Hess grade), and clinical course (e.g., need for gastrostomy or tracheostomy, length of stay). Conditional logistic regression was used to identify significant predictors, accounting for the matched design of the study. RESULTS Among 82 SAH patients with unplanned 30-day readmission, the authors matched 78 patients with 153 nonreadmitted controls. Age, demographics, and socioeconomic factors were not associated with readmission. In univariate analysis, multiple variables were significantly associated with readmission, including Hunt and Hess grade (OR 3.0 for Grade IV/V vs I/II), need for gastrostomy placement (OR 2.0), length of hospital stay (OR 1.03 per day), discharge disposition (OR 3.2 for skilled nursing vs other disposition), and Charlson Comorbidity Index (OR 2.3 for score ≥?2 vs 0). However, the only significant predictor in the multivariate analysis was discharge to a skilled nursing facility (OR 3.2), and the final model was sensitive to criteria used to enter and retain variables. Furthermore, despite the significant association between discharge disposition and readmission, less than 25% of readmitted patients were discharged to a skilled nursing facility. CONCLUSIONS Although discharge disposition remained significant in multivariate analysis, most routinely collected variables appeared to be weak independent predictors of 30-day readmission after SAH. Consequently, hospitals interested in decreasing readmission rates may consider multifaceted, cost-efficient interventions that can be broadly applied to most if not all SAH patients. © AANS, 2017.


Author Keywords
Hospital readmission;  Neurosurgery;  Patient readmission;  Quality indicators (health care);  Subarachnoid hemorrhage;  Vascular disorders


Document Type: Article
Source: Scopus


12) 

Wang, G.a , Cutter, G.R.b , Cofield, S.S.b , Lublin, F.c , Wolinsky, J.S.d , Gustafson, T.c , Krieger, S.c , Salter, A.a 
Baseline EDSS proportions in MS clinical trials affect the overall outcome and power: A cautionary note
(2017) Multiple Sclerosis, 23 (7), pp. 982-987. 

DOI: 10.1177/1352458516670733


a Division of Biostatistics, Washington University in St. Louis, 660 S. Euclid Ave., St. Louis, MO, United States
b Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States
c Icahn School of Medicine at Mount Sinai, New York City, NY, United States
d McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States


Abstract
Background: In randomized clinical trials, when treatments do not work equally effectively across stratifications of participants, observed event rates may differ from those hypothesized leading to deviations in estimated power. Objectives: To investigate the effect of distributions of baseline Expanded Disability Status Scale (EDSS) proportions in relapsing-remitting multiple sclerosis (RRMS) on the trial outcome, confirmed disability progression rate (CDPR), and power. Methods: We reported CDPRs in the CombiRx trial by baseline EDSS and by groups (1st (0, 1), 2nd (1.5, 2), 3rd (2.5, 3), and 4th (≥3/43.5)) and investigated the effect of different combinations of baseline EDSS proportions on the trial outcome and power. Results: There were 244 (25.4%) participants in the 1st group, 368 (38.4%) in the 2nd group, 223 (23.3%) in the 3rd group, and 124 (12.9%) in the 4th group with CDPRs of 40.1%, 13.9%, 11.2%, and 16.9%, respectively. Both CDPR and power increased when the proportion of the 1st group increased in hypothetical trials with equal sample sizes in each arm, and a 10% increase in the 1st group led to a 5% increase in power. Conclusion: Various baseline EDSS proportions yielded different CDPRs and power, suggesting caution in interpretation of treatment effects across trials that enrolled participants with different proportions of baseline EDSS. © SAGE Publications.


Author Keywords
confirmed disability progression rate;  Expanded Disability Status Scale;  Multiple sclerosis;  relapsing-remitting multiple sclerosis


Document Type: Article
Source: Scopus


13) 

Pérez-Carrillo, G.J.G.a , Owen, C.b , Schwetye, K.E.c , McFarlane, S.b , Vellimana, A.K.d , Mar, S.e , Miller-Thomas, M.M.b , Shimony, J.S.b , Smyth, M.D.d , Benzinger, T.L.S.b 
The use of hippocampal volumetric measurements to improve diagnostic accuracy in pediatric patients with mesial temporal sclerosis
(2017) Journal of Neurosurgery: Pediatrics, 19 (6), pp. 720-728. 

DOI: 10.3171/2016.12.PEDS16335


a Department of Medical Imaging, Neuroradiology Section, University of Arizona, Advanced Neuro-Imaging Biometrics Initiative, 1501 N Campbell Ave., Tucson, AZ, United States
b Neuroradiology Section, Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States
c Department of Pathology and Immunology, Washington University, St. Louis, MO, United States
d Department of Neurosurgery, Pediatric Division, St. Louis Children's Hospital, Washington University, St. Louis, MO, United States
e Department of Neurology, Division of Pediatric Neurology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
OBJECTIVE: Many patients with medically intractable epilepsy have mesial temporal sclerosis (MTS), which significantly affects their quality of life. The surgical excision of MTS lesions can result in marked improvement or even complete resolution of the epileptic episodes. Reliable radiological diagnosis of MTS is a clinical challenge. The purpose of this study was to evaluate the utility of volumetric mapping of the hippocampi for the identification of MTS in a case-controlled series of pediatric patients who underwent resection for medically refractory epilepsy, using pathology as a gold standard. METHODS: A cohort of 57 pediatric patients who underwent resection for medically intractable epilepsy between 2005 and 2015 was evaluated. On pathological investigation, this group included 24 patients with MTS and 33 patients with non-MTS findings. Retrospective quantitative volumetric measurements of the hippocampi were acquired for 37 of these 57 patients. Two neuroradiologists with more than 10 years of experience who were blinded to the patients' MTS status performed the retrospective review of MR images. To produce the volumetric data, MR scans were parcellated and segmented using the FreeSurfer software suite. Hippocampal regions of interest were compared against an age-weighted local regression curve generated with data from the pediatric normal cohort. Standard deviations and percentiles of specific subjects were calculated. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for the original clinical read and the expert readers. Receiver operating characteristic curves were generated for the methods of classification to compare results from the readers with the authors' results, and an optimal threshold was determined. From that threshold the sensitivity, specificity, PPV, and NPV were calculated for the volumetric analysis. RESULTS: With the use of quantitative volumetry, a sensitivity of 72%, a specificity of 95%, a PPV of 93%, an NPV of 78%, and an area under the curve of 0.84 were obtained using a percentage difference of normalized hippocampal volume. The resulting specificity (95%) and PPV (93%) are superior to the original clinical read and to Reader A and Reader B's findings (range for specificity 74%-86% and for PPV 64%-71%). The sensitivity (72%) and NPV (78%) are comparable to Reader A's findings (73% and 81%, respectively) and are better than those of the original clinical read and of Reader B (sensitivity 45% and 63% and NPV 71% and 70%, respectively). CONCLUSIONS: Volumetric measurement of the hippocampi outperforms expert readers in specificity and PPV, and it demonstrates comparable to superior sensitivity and NPV. Volumetric measurements can complement anatomical imaging for the identification of MTS, much like a computer-aided detection tool would. The implementation of this approach in the daily clinical workflow could significantly improve diagnostic accuracy. © AANS, 2017.


Author Keywords
Advanced imaging techniques;  Epilepsy surgery;  Magnetic resonance imaging;  Mesial temporal sclerosis


Document Type: Conference Paper
Source: Scopus


14) 

Downes, M.a b , Berg, C.c , Kirkham, F.J.b , Kischkel, L.b , McMurray, I.b , de Haan, M.b 
Task utility and norms for the Preschool Executive Task Assessment (PETA)
(2017) Child Neuropsychology, pp. 1-15. Article in Press. 

DOI: 10.1080/09297049.2017.1333092


a School of Psychology, University College Dublin, Dublin, Ireland
b Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London, UK
c Program in Occupational Therapy, Washington University in St. Louis, St. Louis, MO, USA


Abstract
Earlier identification of executive deficits in preschool children using an ecological approach would give more scope for intervention. The Preschool Executive Task Assessment (PETA) was developed to resemble an everyday age-appropriate task in order to examine the self-direction and integration of executive functions during a multistep task. It was designed so that performance can be evaluated in a microanalytic way and so individualized feedback and support can be easily communicated. The utility of the PETA was assessed with 166 three-to five-year olds. Results showed improved performance with increasing age and verbal intellectual quotient as well as good task reliability and utility. Evidence for influence of socioeconomic status, gender, and use of self-talk was also observed. Clinical applications and future directions of this novel measure are discussed. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
ecological assessment;  Executive function;  neurodevelopmental disorders;  neuropsychological assessment;  preschool


Document Type: Article in Press
Source: Scopus


15) 

Yu, A.B.a b , Zacks, J.M.b 
Transformations and representations supporting spatial perspective taking
(2017) Spatial Cognition and Computation, pp. 1-34. Article in Press. 

DOI: 10.1080/13875868.2017.1322596


a Translational Neuroscience Branch, Army Research Laboratory, Aberdeen Proving Ground, MD, USA
b Department of Psychological & Brain Sciences, Washington University, St. Louis, MO, USA


Abstract
Spatial perspective taking is the ability to reason about spatial relations relative to another’s viewpoint. Here, we propose a mechanistic hypothesis that relates mental representations of one’s viewpoint to the transformations used for spatial perspective taking. We test this hypothesis using a novel behavioral paradigm that assays patterns of response time and variation in those patterns across people. The results support the hypothesis that people maintain a schematic representation of the space around their body, update that representation to take another’s perspective, and thereby to reason about the space around their body. This is a powerful computational mechanism that can support imitation, coordination of behavior, and observational learning. © 2017, Taylor & Francis. All rights reserved.


Author Keywords
mental imagery;  perspective taking;  spatial frameworks;  spatial transformations


Document Type: Article in Press
Source: Scopus


16) 

Camargo, N.a , Goudriaan, A.a , van Deijk, A.-L.F.a , Otte, W.M.b c , Brouwers, J.F.d , Lodder, H.e , Gutmann, D.H.f , Nave, K.-A.g , Dijkhuizen, R.M.b , Mansvelder, H.D.e , Chrast, R.h , Smit, A.B.a , Verheijen, M.H.G.a 
Oligodendroglial myelination requires astrocyte-derived lipids
(2017) PLoS Biology, 15 (5), art. no. e1002605, . 

DOI: 10.1371/journal.pbio.1002605


a Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, Netherlands
b Biomedical MR Imaging and Spectroscopy group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, Netherlands
c Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands
d Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Netherlands
e Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, Netherlands
f Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
g Max-Planck-Institute of Experimental Medicine, Department of Neurogenetics, Goettingen, Germany
h Department of Neuroscience and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden


Abstract
In the vertebrate nervous system, myelination of axons for rapid impulse propagation requires the synthesis of large amounts of lipids and proteins by oligodendrocytes and Schwann cells. Myelin membranes are thought to be cell-autonomously assembled by these axon-associated glial cells. Here, we report the surprising finding that in normal brain development, a substantial fraction of the lipids incorporated into central nervous system (CNS) myelin are contributed by astrocytes. The oligodendrocyte-specific inactivation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription factor SREBP and thus of lipid biosynthesis, resulted in significantly retarded CNS myelination; however, myelin appeared normal at 3 months of age. Importantly, embryonic deletion of the same gene in astrocytes, or in astrocytes and oligodendrocytes, caused a persistent hypomyelination, as did deletion from astrocytes during postnatal development. Moreover, when astroglial lipid synthesis was inhibited, oligodendrocytes began incorporating circulating lipids into myelin membranes. Indeed, a lipid-enriched diet was sufficient to rescue hypomyelination in these conditional mouse mutants. We conclude that lipid synthesis by oligodendrocytes is heavily supplemented by astrocytes in vivo and that horizontal lipid flux is a major feature of normal brain development and myelination. © 2017 Public Library of Science. All Rights Reserved.


Document Type: Article
Source: Scopus


17) 

Yano, M., Misra, S., Salter, A., Carpenter, D.H.
Assessment of disease aggression in cystic pancreatic neuroendocrine tumors: A CT and pathology correlation study
(2017) Pancreatology, . Article in Press. 

DOI: 10.1016/j.pan.2017.05.388


Washington University School of Medicine, USA


Abstract
Background/Objectives: There are inconsistencies in the literature regarding the clinical significance of cystic components in pancreatic neuroendocrine tumors (NET). This may be related to differences in the identification of cystic NET through imaging and/or pathology. Tumors may also be microscopically or macroscopically cystic. Our primary objective is to determine radiology-pathology correlation for the identification of cystic components. Our secondary objective is to determine if cystic components are associated with indices of tumor aggression. Methods: 60 tumors with correlative surgical pathology were assessed retrospectively for cystic components on CT and pathology. Tumor was categorized as solid or cystic on CT and pathology. If cystic on pathology, cystic components were categorized as macroscopic or microscopic. Cystic components were estimated as <50% and ≥50% tumor volume. WHO/Hochwald grade and presence of metastases were used to stratify disease aggression. Associations were tested with Chi square/Fisher's exact test and differences were tested with t-test/Wilcoxon rank sums test. Results: There is moderate agreement between CT and histology for presence of cystic components. Discrepancies were mostly attributable to the presence of microscopic cystic components in tumors appearing solid on CT. There was no difference in size between cystic and solid tumors on CT or pathology. No association between CT-determined cystic components and tumor grade was found. Tumors with cystic components (cystic by CT, and macroscopically cystic by pathology) demonstrated less association with metastases than solid tumors. Conclusions: Cystic components, comprising ≥50% of the tumor by CT and observed macroscopically on pathology, are associated with less aggressive disease. © 2017 IAP and EPC.


Author Keywords
Bioimaging;  Cystic neuroendocrine tumor;  Hochwald grade;  Metastases;  WHO grade


Document Type: Article in Press
Source: Scopus


18) 

Odom, E.B.a , Eisenberg, D.L.b , Fox, I.K.a 
Difficult removal of subdermal contraceptive implants: A multidisciplinary approach involving a peripheral nerve expert
(2017) Contraception, . Article in Press. 

DOI: 10.1016/j.contraception.2017.05.001


a Washington University School of Medicine, Division of Plastic and Reconstructive Surgery
b Washington University School of Medicine, Department of Obstetrics and Gynecology


Abstract
Objectives: We aim to describe our experiences and identify patients who may benefit from referral to a peripheral nerve surgeon for removal of contraceptive subdermal implants in which neurovascular injury may occur, and describe a treatment pathway for optimal care. Study design: We reviewed the charts of 22 patients who were referred to the Division of Family Planning for difficult removal of etonogestrel contraceptive implants between January 1, 2014, and April, 1 2016. Of these, five were referred to a peripheral nerve surgeon due to pain or location of the implant. We evaluated and described these cases and, from our findings, developed recommendations for care in a multidisciplinary team approach. Results: Two patients reported pain, including one with four previous failed removal attempts. In the two patients with pain, the implants were adherent to a sensory nerve. In another, the implant was within the biceps muscle and difficult to locate. In all cases, ultrasound imaging, general anesthesia and a wide exposure allowed for safe removal and good outcomes. Our multidisciplinary care approach has elucidated important referral and technical considerations that improve patient care and safety. Conclusion: When necessary, multidisciplinary care with a Family Planning expert and possibly a peripheral nerve surgeon may be beneficial in safely removing etonogestrel contraceptive implants that would be difficult or risky to remove in an ambulatory setting. © 2017.


Author Keywords
Difficult implant removal;  Etonogestrel contraceptive implant;  Implanon;  Multidisciplinary care;  Nerve injury


Document Type: Article in Press
Source: Scopus


19) 

Keren-Shaul, H.a , Spinrad, A.a b , Weiner, A.a c , Matcovitch-Natan, O.a b , Dvir-Szternfeld, R.b , Ulland, T.K.d , David, E.a , Baruch, K.b , Lara-Astaiso, D.a , Toth, B.e , Itzkovitz, S.e , Colonna, M.d , Schwartz, M.b , Amit, I.a 
A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease
(2017) Cell, . Article in Press. 

DOI: 10.1016/j.cell.2017.05.018


a Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel
b Department of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel
c Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), and University Medical Center, Cancer Genomics Netherlands, 3584 CG Utrecht, the Netherlands
d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
e Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel


Abstract
Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices shows DAM with intracellular/phagocytic Aβ particles. Single-cell analysis of DAM in Tg-AD and triggering receptor expressed on myeloid cells 2 (Trem2)-/- Tg-AD reveals that the DAM program is activated in a two-step process. Activation is initiated in a Trem2-independent manner that involves downregulation of microglia checkpoints, followed by activation of a Trem2-dependent program. This unique microglia-type has the potential to restrict neurodegeneration, which may have important implications for future treatment of AD and other neurodegenerative diseases. Video Abstract: Display Omitted. A new type of microglia associated with restricting neurodegeneration may have important implications for treatment of Alzheimer's and related diseases. © 2017 Elsevier Inc.


Author Keywords
Alzheimer's disease;  Immunology;  Microglia;  Single cell RNA-seq;  Systems biology


Document Type: Article in Press
Source: Scopus


20) 

Jung, Y.a , Boot, B.P.b , Mielke, M.M.c , Ferman, T.J.d , Geda, Y.E.e f , McDade, E.g , Christianson, T.J.H.c , Knopman, D.S.a , St Louis, E.K.a h , Silber, M.H.a h , Petersen, R.C.a , Boeve, B.F.a h 
Phenoconversion from probable rapid eye movement sleep behavior disorder to mild cognitive impairment to dementia in a population-based sample
(2017) Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 8, pp. 127-130. 

DOI: 10.1016/j.dadm.2017.05.004


a Department of Neurology, Mayo Clinic, Rochester, MN, United States
b Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States
c Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States
d Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, United States
e Department of Psychiatry and Psychology, Mayo Clinic, Scottsdale, AZ, United States
f Department of Neurology, Mayo Clinic, Scottsdale, AZ, United States
g Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
h Center for Sleep Medicine, Mayo Clinic, Rochester, MN, United States


Abstract
Introduction Rapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes. Methods Fifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed. Results Over 6.4 ± 2.9 years, six of the 14 participants with MCI developed additional neurodegenerative signs, five of whom had Lewy body disease features. Four of them progressed to dementia at a mean age 84.8 ± 4.9 years, three of whom met the criteria for probable dementia with Lewy bodies. One subject with PD developed MCI, but not dementia. Discussion Our findings from the population-based sample of Olmsted County, Minnesota, residents suggest that a substantial number of RBD patients tend to develop overt synucleinopathy features over time, and RBD patients who develop MCI and subsequent dementia have clinical features most consistent with dementia with Lewy bodies. © 2017 The Authors


Author Keywords
Dementia with Lewy bodies;  Mild cognitive impairment;  Parkinson disease;  Rapid eye movement sleep behavior disorder;  Synucleinpathy


Document Type: Article
Source: Scopus


21) 

Alminhana, L.O.a , Farias, M.b , Claridge, G.c , Cloninger, C.R.d , Moreira-Almeida, A.e 
How to tell a happy from an unhappy schizotype: Personality factors and mental health outcomes in individuals with psychotic experiences
(2017) Revista Brasileira de Psiquiatria, 39 (2), pp. 126-132. 

DOI: 10.1590/1516-4446-2016-1944


a Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
b Coventry University, Coventry, United Kingdom
c Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom
d Washington University in Saint Louis, St. Louis, MO, United States
e Faculdade de Medicina, Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, MG, Brazil


Abstract
Objective: It is unclear why some individuals reporting psychotic experiences have balanced lives while others go on to develop mental health problems. The objective of this study was to test if the personality traits of harm avoidance, self-directedness, and self-transcendence can be used as criteria to differentiate healthy from unhealthy schizotypal individuals. Methods: We interviewed 115 participants who reported a high frequency of psychotic experiences. The instruments used were the Temperament and Character Inventory (140), Structured Clinical Interview for DSM-IV, and the Oxford-Liverpool Inventory of Feelings and Experiences. Results: Harm avoidance predicted cognitive disorganization (β = 0.319; t = 2.94), while novelty seeking predicted bipolar disorder (β = 0.136, Exp [b] = 1.146) and impulsive non-conformity (β = 0.322; t = 3.55). Self-directedness predicted an overall decrease in schizotypy, most of all in cognitive disorganization (β = -0.356; t = -2.95) and in impulsive non-conformity (β = -0.313; t = -2.83). Finally, self-transcendence predicted unusual experiences (β = 0.256; t = 2.32). Conclusion: Personality features are important criteria to distinguish between pathology and mental health in individuals presenting high levels of anomalous experiences (AEs). While self-directedness is a protective factor, both harm avoidance and novelty seeking were predictors of negative mental health outcomes. We suggest that the impact of AEs on mental health is moderated by personality factors. © 2017, Associacao Brasileira de Psiquiatria. All rights reserved.


Author Keywords
Diagnosis and classification;  Outpatient psychiatry;  Personality disorders - cluster a (paranoid-schizoid-schizotypal);  Psychosis;  Religion


Document Type: Article
Source: Scopus


22) 

Babulal, G.M.a b , Stout, S.H.a b , Head, D.a d e , Holtzman, D.M.a b c , Fagan, A.M.a b c , Morris, J.C.a b c f g h , Roe, C.M.a b 
Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers Predict Driving Decline: Brief Report
(2017) Journal of Alzheimer's Disease, 58 (3), pp. 675-680. 

DOI: 10.3233/JAD-170067


a Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO, United States
b Department of Neurology, 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 Department of Psychological and Brain Sciences, Washington University School of Medicine, St. Louis, MO, United States
e Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
h Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States


Abstract
We examined whether neuropsychiatric symptoms (NPS) interact with cerebrospinal fluid (CSF) biomarkers (amyloid-β42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, and ptau181/Aβ42) of Alzheimer's disease pathology to predict driving decline among cognitively-normal older adults (N=116) aged ≥65. Cox proportional hazards models examined time to receiving a rating of marginal or fail on the driving test. Age, education, and gender were adjusted in the models. Participants with more abnormal CSF (Aβ42, tau/Aβ42, ptau181/Aβ42) and NPS were faster to receive a marginal/fail on the road test compared to those without NPS. NPS interact with abnormal CSF biomarkers to impact driving performance among cognitively-normal older adults. © 2017 - IOS Press and the authors. All rights reserved.


Author Keywords
Alzheimer's disease;  cerebrospinal fluid;  depression;  neuropsychology;  noncognitive outcomes;  preclinical


Document Type: Article
Source: Scopus


23) 

Toonen, J.A., Ma, Y., Gutmann, D.H.
Defning the temporal course of murine neurofbromatosis-1 optic gliomagenesis reveals a therapeutic window to attenuate retinal dysfunction
(2017) Neuro-Oncology, 19 (6), pp. 808-819. 

DOI: 10.1093/neuonc/now267


Department of Neurology, Washington University School of Medicine (WUSM), Box 8111 660 S. Euclid Avenue, St Louis, MO, United States


Abstract
Background. Optic gliomas arising in the neurofbromatosis type 1 (NF1) cancer predisposition syndrome cause reduced visual acuity in 30%-50% of affected children. Since human specimens are rare, genetically engineered mouse (GEM) models have been successfully employed for preclinical therapeutic discovery and validation. However, the sequence of cellular and molecular events that culminate in retinal dysfunction and vision loss has not been fully defned relevant to potential neuroprotective treatment strategies. Methods. Nf1fox/mut GFAP-Cre (FMC) mice and age-matched Nf1fox/fox (FF) controls were euthanized at defned intervals from 2 weeks to 24 weeks of age. Optic nerve volumes were measured, and optic nerves/retinae analyzed by immunohistochemistry. Optical coherence tomography (OCT) was performed on anesthetized mice. FMC mice were treated with lovastatin from 12 to 16 weeks of age. Results. The earliest event in tumorigenesis was a persistent elevation in proliferation (4 wk), which preceded sustained microglia numbers and incremental increases in S100+ glial cells. Microglia activation, as evidenced by increased interleukin (IL)-1β expression and morphologic changes, coincided with axonal injury and retinal ganglion cell (RGC) apoptosis (6 wk). RGC loss and retinal nerve fber layer (RNFL) thinning then ensued (9 wk), as revealed by direct measurements and live-animal OCT. Lovastatin administration at 12 weeks prevented further RGC loss and RNFL thinning both immediately and 8 weeks after treatment completion. Conclusion. By defning the chronology of the cellular and molecular events associated with optic glioma pathogenesis, we demonstrate critical periods for neuroprotective intervention and visual preservation, as well as establish OCT as an accurate biomarker of RGC loss. © 2017 The Author(s).


Author Keywords
optic glioma;  Optical coherence tomography;  Pediatric brain tumor;  Retinal ganglion cell;  Retinal nerve fber layer


Document Type: Article
Source: Scopus


24) 

Yao, J.a , Zou, J.b , Wang, L.V.c 
Wide-field fast-scanning photoacoustic microscopy of brain functions in action
(2017) Optics InfoBase Conference Papers, Part F43-CLEO_AT 2017, 2 p. 

DOI: 10.1364/CLEO_AT.2017.ATu1B.5


a Department of Biomedical Engineering, Duke University, Durham, NC, United States
b Department of Electrical and Computer Engineering, Texas A and M University, College Station, TX, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States


Abstract
We have developed fast functional photoacoustic microscopy for 3D highresolution high-speed imaging of the mouse brain. In particular, a novel single-wavelength pulsewidth- based method can image blood oxygenation with capillary-level resolution at 100 kHz frame rate. © 2017 OSA.


Document Type: Conference Paper
Source: Scopus


25) 

Paniagua, B.a , Kim, S.b , Moustapha, M.b , Styner, M.b , Cody-Hazlett, H.c , Gimple-Smith, R.c , Rumple, A.b , Piven, J.c , Gilmore, J.b , Skolnick, G.d , Patel, K.d 
Brain structure in sagittal craniosynostosis
(2017) Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 10137, art. no. 101370O, . 

DOI: 10.1117/12.2254442


a Kitware Inc., 101 Weaver St Suite G4, Carrboro, NC, United States
b University of North Carolina, School of Medicine, Department of Psychiatry, 101 Manning Drive, Chapel Hill, NC, United States
c Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, 100 Renee Lynn Ct, Chapel Hill, NC, United States
d Washington University in St. Louis, Department of Plastic and Reconstructive Surgery, School of Medicine, 660 South Euclid Ave., St. Louis, MO, United States


Abstract
Craniosynostosis, the premature fusion of one or more cranial sutures, leads to grossly abnormal head shapes and pressure elevations within the brain caused by these deformities. To date, accepted treatments for craniosynostosis involve improving surgical skull shape aesthetics. However, the relationship between improved head shape and brain structure after surgery has not been yet established. Typically, clinical standard care involves the collection of diagnostic medical computed tomography (CT) imaging to evaluate the fused sutures and plan the surgical treatment. CT is known to provide very good reconstructions of the hard tissues in the skull but it fails to acquire good soft brain tissue contrast. This study intends to use magnetic resonance imaging to evaluate brain structure in a small dataset of sagittal craniosynostosis patients and thus quantify the effects of surgical intervention in overall brain structure. Very importantly, these effects are to be contrasted with normative shape, volume and brain structure databases. The work presented here wants to address gaps in clinical knowledge in craniosynostosis focusing on understanding the changes in brain volume and shape secondary to surgery, and compare those with normally developing children. This initial pilot study has the potential to add significant quality to the surgical care of a vulnerable patient population in whom we currently have limited understanding of brain developmental outcomes. © 2017 SPIE.


Author Keywords
Brain Tissue segmentation;  Computer Assisted Intervention Planning;  Full vault reconstructive surgery;  Osteoarthritis;  Sagittal craniosynostosis;  Statistical Shape Analysis


Document Type: Conference Paper
Source: Scopus


 

26) 

Grattan, E.S.a , Lang, C.E.b , Birkenmeier, R.c , Holm, M.d , Rubinstein, E.e , Van Swearingen, J.f , Skidmore, E.R.g 
Examining the Feasibility, Tolerability, and Preliminary Efficacy of Repetitive Task-Specific Practice for People With Unilateral Spatial Neglect
(2016) The American journal of occupational therapy : official publication of the American Occupational Therapy Association, 70 (4), pp. p1-p8. 

DOI: 10.5014/ajot.2016.019471


a Emily S. Grattan, PhD, OTR/L, is Postdoctoral Scholar, Department of Health Science and Research, Medical University of South Carolina, Charleston;
b Catherine E. Lang, PT, PhD, is Professor, Program in Physical Therapy and Program in Occupational Therapy, Department of Neurology, Washington University School of Medicine, St. Louis, MO
c Rebecca Birkenmeier, OTD, OTR/L, is Assistant Professor, Program of Occupational Therapy, Maryville University, St. Louis, MO
d Margo Holm, PhD, OTR/L, is Professor Emerita, Department of Occupational Therapy, University of Pittsburgh, Pittsburgh, PA
e Elaine Rubinstein, PhD, is Lecturer, Department of Psychology, Chatham University, and Senior Service Fellow, Office of Mine Safety and Health Research, Bruceton Research Center, National Institute for Occupational Safety and Health, Pittsburgh, PA
f Jessie Van Swearingen, PT, PhD, is Associate Professor, Department of Physical Therapy, University of Pittsburgh, Pittsburgh, PA
g Elizabeth R. Skidmore, PhD, OTR/L, is Associate Professor and Chair, Department of Occupational Therapy, University of Pittsburgh, Pittsburgh, PA


Abstract
OBJECTIVE: We examined the feasibility, tolerability, and preliminary efficacy of repetitive task-specific practice for people with unilateral spatial neglect (USN).

METHOD: People with USN ≥6 mo poststroke participated in a single-group, repeated-measures study. Attendance, total repetitions, and satisfaction indicated feasibility and pain indicated tolerability. Paired t tests and effect sizes were used to estimate changes in upper-extremity use (Motor Activity Log), function (Action Research Arm Test), and attention (Catherine Bergego Scale).

RESULTS: Twenty participants attended 99.4% of sessions and completed a high number of repetitions. Participants reported high satisfaction and low pain, and they demonstrated small, significant improvements in upper-extremity use (before Bonferroni corrections; t = -2.1, p = .04, d = .30), function (t = -3.0, p < .01, d = .20), and attention (t = -3.4, p < .01, d = -.44).

CONCLUSION: Repetitive task-specific practice is feasible and tolerable for people with USN. Improvements in upper-extremity use, function, and attention may be attainable. Copyright © 2016 by the American Occupational Therapy Association, Inc.


Document Type: Article
Source: Scopus

June 19, 2017

1) 

Xue, Y.a f , Sato, S.a , Razafsky, D.a g , Sahu, B.b , Shen, S.Q.c , Potter, C.a , Sandell, L.L.d , Corbo, J.C.c , Palczewski, K.e , Maeda, A.b e , Hodzic, D.a , Kefalov, V.J.a 
The role of retinol dehydrogenase 10 in the cone visual cycle
(2017) Scientific Reports, 7 (1), art. no. 2390, . 

DOI: 10.1038/s41598-017-02549-8


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Oral Immunology and Infectious Diseases, University of Louisville, Louisville, KY, United States
e Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, OH, United States
f Department of Genetics, Harvard Medical School, Boston, MA, United States
g MilliporeSigma, St. Louis, MO, United States


Abstract
Pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-Trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. However, the enzyme responsible for the oxidation of 11-cis-retinol remains unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10), upregulated in rod/cone hybrid retinas and expressed abundantly in Müller cells, is the enzyme that drives this reaction. We created mice lacking RDH10 either in cone photoreceptors, Müller cells, or the entire retina. In vivo electroretinography and transretinal recordings revealed normal cone photoresponses in all RDH10-deficient mouse lines. Notably, their cone-driven dark adaptation both in vivo and in isolated retina was unaffected, indicating that RDH10 is not required for the function of the retina visual cycle. We also generated transgenic mice expressing RDH10 ectopically in rod cells. However, rod dark adaptation was unaffected by the expression of RDH10 and transgenic rods were unable to use cis-retinol for pigment regeneration. We conclude that RDH10 is not the dominant retina 11-cis-RDH, leaving its primary function in the retina unknown. © 2017 The Author(s).


Document Type: Article
Source: Scopus


2) 

Cicero, T.J., Ellis, M.S., Kasper, Z.A.
Increased use of heroin as an initiating opioid of abuse
(2017) Addictive Behaviors, 74, pp. 63-66. 

DOI: 10.1016/j.addbeh.2017.05.030


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


Abstract
Introduction Given the relatively recent growth in access to heroin and a more permissive atmosphere surrounding its use, we hypothesized that an increasing number of persons with limited experience and tolerance to opioids would experiment with heroin as their first opioid rather than more common prescription opioid analgesics. Methods Individuals entering substance abuse treatment for an opioid use disorder in the period 2010–2016 (N = 5885) were asked about the specific opioid they first regularly used to get high. To limit long-term recall and survival bias, analyses was restricted to opioid initiation that occurred in the past ten years (2005–2015). Results In 2005, only 8.7% of opioid initiators started with heroin, but this sharply increased to 33.3% (p < 0.001) in 2015, with no evidence of stabilization. The use of commonly prescribed opioids, oxycodone and hydrocodone, dropped from 42.4% and 42.3% of opioid initiators, respectively, to 24.1% and 27.8% in 2015, such that heroin as an initiating opioid was now more frequently endorsed than prescription opioid analgesics. Conclusions Our data document that, as the most commonly prescribed opioids – hydrocodone and oxycodone – became less accessible due to supply-side interventions, the use of heroin as an initiating opioid has grown at an alarming rate. Given that opioid novices have limited tolerance to opioids, a slight imprecision in dosing inherent in heroin use is likely to be an important factor contributing to the growth in heroin-related over dose fatalities in recent years. © 2017


Author Keywords
Heroin;  Heroin overdose;  Opioid abuse;  Opioid initiation;  Prescription opioid abuse


Document Type: Article
Source: Scopus


3) 

Wright, P.W.a , Archambault, A.S.b , Peek, S.c , Bauer, A.Q.a , Culican, S.M.c , Ances, B.M.a b , Culver, J.P.a , Wu, G.F.b d 
Functional connectivity alterations in a murine model of optic neuritis
(2017) Experimental Neurology, 295, pp. 18-22. 

DOI: 10.1016/j.expneurol.2017.05.004


a Department of Radiology, Washington University in St. Louis School of Medicine, United States
b Department of Neurology, Washington University in St. Louis School of Medicine, United States
c Department of Ophthalmology, Washington University in St. Louis School of Medicine, United States
d Department of Pathology & Immunology, Washington University in St. Louis School of Medicine, United States


Abstract
The basis for neuronal dysfunction following inflammatory demyelination of the central nervous system (CNS) remains poorly understood. We characterized the network response to white matter injury in the anterior visual pathway using an experimental model of optic neuritis (ON), as ON is often an early manifestation of immune-mediated CNS demyelination in multiple sclerosis (MS). Optical intrinsic signal imaging was performed before and after the induction of ON in mice to measure changes in cortical network functional connectivity. We observed a greater loss of connectivity between homotopic visual cortices in ON mice compared to controls. Further, decreases in homotopic visual cortex connectivity were associated with visual acuity loss in ON mice. These results demonstrate that network connectivity changes resulting from ON can be modeled in an experimental murine system. Future studies will identify the mechanisms that cause neuronal dysfunction due to white matter injury seen in MS. © 2017 Elsevier Inc.


Author Keywords
Demyelination;  Functional connectivity;  Multiple sclerosis;  Optic neuritis;  Optical imaging;  Visual cortex


Document Type: Article
Source: Scopus


4) 

Adam, E.K.a , Quinn, M.E.b c , Tavernier, R.d , McQuillan, M.T.a , Dahlke, K.A.e , Gilbert, K.E.f 
Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis
(2017) Psychoneuroendocrinology, 83, pp. 25-41. 

DOI: 10.1016/j.psyneuen.2017.05.018


a School of Education and Social Policy and Institute for Policy Research, Northwestern University, 2120 Campus Drive, Evanston, IL, United States
b Department of Psychology, Northwestern University, 2029 Sheridan Rd., Evanston, IL, United States
c Department of Psychiatry, University of Illinois at Chicago, 912 S. Wood St., Chicago, IL, United States
d Department of Psychology, Wesleyan University, 207 High Street, Middletown, CT, United States
e American Institutes for Research, 1120 E. Diehl Road, Suite 200, Naperville, IL, United States
f Department of Psychiatry, Washington University in St. Louis, 4444 Forest Park Parkway, Suite 2100, St. Louis, MO, United States


Abstract
Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been proposed as a mediator between chronic psychosocial stress and poor mental and physical health outcomes in past theory and research. Surprisingly, neither a systematic nor a meta-analytic review of associations between diurnal cortisol slopes and health has been conducted to date, despite extensive literature on the topic. The current systematic review and meta-analysis examined associations between diurnal cortisol slopes and physical and mental health outcomes. Analyses were based on 179 associations from 80 studies for the time period up to January 31, 2015. Results indicated a significant association between flatter diurnal cortisol slopes and poorer health across all studies (average effect size, r = 0.147). Further, flatter diurnal cortisol slopes were associated with poorer health in 10 out of 12 subtypes of emotional and physical health outcomes examined. Among these subtypes, the effect size was largest for immune/inflammation outcomes (r = 0.288). Potential moderators of the associations between diurnal cortisol slopes and health outcomes were examined, including type of slope measure and study quality indices. The possible roles of flatter slopes as either a marker or a mechanism for disease etiology are discussed. We argue that flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms, with corresponding downstream effects on multiple aspects of biology, behavior, and health. © 2017 Elsevier Ltd


Author Keywords
Circadian rhythms;  Diurnal cortisol slopes;  Hypothalamic pituitary adrenal (HPA) axis;  Mental health;  Physical health


Document Type: Review
Source: Scopus


5) 

Cicero, T.J., Ellis, M.S., Kasper, Z.A.
Increases in self-reported fentanyl use among a population entering drug treatment: The need for systematic surveillance of illicitly manufactured opioids
(2017) Drug and Alcohol Dependence, 177, pp. 101-103. 

DOI: 10.1016/j.drugalcdep.2017.04.004


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


Abstract
Background/purpose Recent reports indicate a sharp increase in fentanyl-related overdose deaths across the United States, much of which is likely related to the introduction of cheap, illicitly manufactured fentanyl derivatives. In this study, we sought to estimate the magnitude of illicit fentanyl use from 2012 to 2016 using a national opioid abuse surveillance system. Methods The study program surveyed 10,900 individuals entering substance abuse treatment for opioid use disorder, with participants asked to endorse past month ‘use to get high’ of fentanyl drugs, stratified by identifiable (i.e., branded) fentanyl formulations or a ‘type unknown’ drug alleged to contain fentanyl. Main findings Total past-month fentanyl-use rose modestly from 2012 to 2016. While use of known fentanyl products remained relatively stable (mean = 10.9%; P = 0.25), endorsements of ‘unknown’ fentanyl products nearly doubled from 9% in 2013 to 15.1% by 2016 (P < 0.001). Data show no discernable indication that this increase is diminishing or stabilizing. Conclusions This first attempt to assess the prevalence of illicit fentanyl use shows that recent increases in fentanyl use seem to be due almost entirely to ‘unknown’ fentanyl presumed to be illicitly manufactured. Given that it is difficult to assess the extent to which fentanyl may have been substituted for another drug (i.e., oxycodone, alprazolam, etc.) or was used as a heroin admixture, our data likely represent an underestimation of the full magnitude of illicit fentanyl abuse. As such, this growing public health problem requires immediate attention and more systematic efforts to identify and track its abuse. © 2017


Author Keywords
Epidemiology;  Fentanyl;  Illicit fentanyl;  Opioid abuse;  Synthetic opioids


Document Type: Article
Source: Scopus


6) 

Wysocki, T.
Arguments over Intuitions?
(2017) Review of Philosophy and Psychology, 8 (2), pp. 477-499. 

DOI: 10.1007/s13164-016-0301-8


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


Abstract
Deutsch 2010 (The Review of Philosophy and Psychology 1: 447–460) claims that hypothetical scenarios are evaluated using arguments, not intuitions, and therefore experiments on intuitions are philosophically inconsequential. Using the Gettier case as an example, he identifies three arguments that are supposed to point to the right response to the case. In the paper, I present the results of studies ran on Polish, Indian, Spanish, and American participants that suggest that there’s no deep difference between evaluating the Gettier case with intuitions and evaluating it with Deutsch’s arguments. Specifically, I argue that one would find these arguments persuasive if and only if one is already disposed to exhibit the relevant intuition. © 2016, Springer Science+Business Media Dordrecht.


Document Type: Article
Source: Scopus


7) 

Welch, R.D.a b , Ellis, M.a , Lewis, L.M.c , Ayaz, S.I.a , Mika, V.H.a , Millis, S.a d , Papa, L.e 
Modeling the Kinetics of Serum Glial Fibrillary Acidic Protein, Ubiquitin Carboxyl-Terminal Hydrolase-L1, and S100B Concentrations in Patients with Traumatic Brain Injury
(2017) Journal of Neurotrauma, 34 (11), pp. 1957-1971. 

DOI: 10.1089/neu.2016.4772


a Department of Emergency Medicine, Wayne State University School of Medicine, Cardiovascular Research Institute, 4201 St. Antoine, Detroit, MI, United States
b Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, United States
c Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, United States
d Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine, Detroit, MI, United States
e Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL, United States


Abstract
Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), and S100B have been shown to be predictive of patients with brain injury. Kinetics of these biomarkers in injured humans have not been extensively examined. This prospective multi-center study included patients with mild-to-moderate traumatic brain injury. Blood samples obtained at enrollment and every 6 h up to 24 h post-injury were assayed for GFAP, UCH-L1, and S100B. Random effects models examined changes in the biomarkers' level over time. A total of 167 patients were enrolled; mean age was 46.0 ± 17.8, 61.1% were male, 143 (85.6%) had a Glasgow Coma Scale score of 15, and 33 (19.8%) had a positive head computed tomography (CT) scan. Baseline median biomarker concentrations for all three were higher among CT-positive patients (p < 0.0001) but GFAP was the only biomarker that significantly increased over time among CT-positive patients relative to CT-negative patients (log transformed values 0.037; 95% confidence interval 0.02, 0.05; p < 0.001), indicating a 3.7% per hour rise in GFAP concentration. There was no significant increase in either UCH-L1 or S100B in CT-positive patients (p = 0.15 and p = 0.47, respectively). GFAP concentrations increased 3.7% per hour among CT-positive patients whereas neither UCH-L1 nor S100B increased, compared with CT-negative patients. The kinetics and temporal profile of GFAP suggest it may be a more robust biomarker to detect patients with positive CT findings, particularly at later post-injury times. Further study is needed to determine if GFAP is a useful test to follow throughout a patient's clinical course. © 2017, Mary Ann Liebert, Inc.


Author Keywords
biomarkers;  glia cell response to injury;  neural injury;  traumatic brain injury


Document Type: Article
Source: Scopus


8) 

Kwon, E.a , Park, S.b 
Heterogeneous trajectories of physical and mental health in late middle age: Importance of life-course socioeconomic positions
(2017) International Journal of Environmental Research and Public Health, 14 (6), art. no. 582, . 

DOI: 10.3390/ijerph14060582


a Center for Social Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, South Korea
b George Warren Brown School of Social Work, Washington University, One Brookings Drive, Saint Louis, MO, United States


Abstract
Drawing on life course and cumulative disadvantage theory, this study examines heterogeneous trajectories of functional limitations and depressive symptoms among late middle-aged individuals. This study used prospective data from 6010 adults, 51 to 64 years old, collected over a 12-year-period from the Health and Retirement Study. Considering the empirical proposition that several physical and mental trajectories may exist, Latent Class Growth Modeling was used. Five heterogeneous patterns of joint trajectories (Relatively healthy, Moderately improving, Steadily deteriorating, Steeply deteriorating, and Persistently high comorbid) were identified. Early life adversity was related to an increasing risk of declines in physical and mental health. The Persistently high comorbid class was characterized by a concentration of disadvantages over the life course. The development of public health interventions could help reduce co-existing physical and mental health problems, especially during late middle-age. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.


Author Keywords
Cumulative disadvantage;  Health disparities;  Heterogeneous trajectories of physical and mental health;  Late middle age;  Life course


Document Type: Article
Source: Scopus


9) 

Lean, R.E.a , Melzer, T.R.b c , Bora, S.d , Watts, R.e , Woodward, L.J.f g 
Attention and Regional Gray Matter Development in Very Preterm Children at Age 12 Years
(2017) Journal of the International Neuropsychological Society, pp. 1-12. Article in Press. 

DOI: 10.1017/S1355617717000388


a Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
b Department of Medicine, University of Otago, Christchurch, New Zealand
c New Zealand Brain Research Institute, Christchurch, New Zealand
d Mothers, Babies and Women’s Health Program, Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia
e Department of Radiology, University of Vermont, Burlington, Vermont
f Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
g Department of Psychology, University of Canterbury, Christchurch, New Zealand


Abstract
Objectives: This study examines the selective, sustained, and executive attention abilities of very preterm (VPT) born children in relation to concurrent structural magnetic resonance imaging (MRI) measures of regional gray matter development at age 12 years. Methods: A regional cohort of 110 VPT (≤32 weeks gestation) and 113 full term (FT) born children were assessed at corrected age 12 years on the Test of Everyday Attention-Children. They also had a structural MRI scan that was subsequently analyzed using voxel-based morphometry to quantify regional between-group differences in cerebral gray matter development, which were then related to attention measures using multivariate methods. Results: VPT children obtained similar selective (p=.85), but poorer sustained (p=.02) and executive attention (p=.01) scores than FT children. VPT children were also characterized by reduced gray matter in the bilateral parietal, temporal, prefrontal and posterior cingulate cortices, bilateral thalami, and left hippocampus; and increased gray matter in the occipital and anterior cingulate cortices (family-wise error–corrected p<.05). Poorer sustained auditory attention was associated with increased gray matter in the anterior cingulate cortex (p=.04). Poor executive shifting attention was associated with reduced gray matter in the right superior temporal cortex (p=.04) and bilateral thalami (p=.05). Poorer executive divided attention was associated with reduced gray matter in the occipital (p=.001), posterior cingulate (p=.02), and left temporal (p=.01) cortices; and increased gray matter in the anterior cingulate cortex (p=.001). Conclusions: Disturbances in regional gray matter development appear to contribute, at least in part, to the poorer attentional performance of VPT children at school age. (JINS, 2017, 23, 1–12) Copyright © The International Neuropsychological Society 2017


Author Keywords
Attention;  Brain;  Gray matter;  MRI;  Outcome;  Very preterm


Document Type: Article in Press
Source: Scopus


10) 

Hoye, M.L.a , Koval, E.D.a , Wegener, A.J.a , Hyman, T.S.a , Yang, C.b , O’Brien, D.R.b , Miller, R.L.a , Cole, T.c , Schoch, K.M.a , Shen, T.a , Kunikata, T.a , Richard, J.-P.d , Gutmann, D.H.a , Maragakis, N.J.d , Kordasiewicz, H.B.c , Dougherty, J.D.b , Miller, T.M.a 
MicroRNA profiling reveals marker of motor neuron disease in ALS models
(2017) Journal of Neuroscience, 37 (22), pp. 5574-5586. 

DOI: 10.1523/JNEUROSCI.3582-16.2017


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Genetics, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Ionis Pharmaceuticals, Carlsbad, CA, United States
d Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MO, United States


Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. Micron RNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents. © 2017 the authors.


Author Keywords
ALS;  MicroRNAs;  MiRAP;  Motor neuron;  Motor neuron disease;  TRAP


Document Type: Article
Source: Scopus


11) 

Duan, C.a , Kallehauge, J.F.b c , Pérez-Torres, C.J.d e , Bretthorst, G.L.f , Beeman, S.C.d , Tanderup, K.c f g , Ackerman, J.J.H.a d h i , Garbow, J.R.d i 
Modeling Dynamic Contrast-Enhanced MRI Data with a Constrained Local AIF
(2017) Molecular Imaging and Biology, pp. 1-10. Article in Press. 

DOI: 10.1007/s11307-017-1090-x


a Department of Chemistry, Washington University, Saint Louis, MO, United States
b Department of Medical Physics, Aarhus University, Aarhus, Denmark
c Department of Oncology, Aarhus University, Aarhus, Denmark
d Department of Radiology, Washington University, Saint Louis, MO, United States
e School of Health Sciences, Purdue University, West Lafayette, IN, United States
f Department of Radiation Oncology, Washington University, Saint Louis, MO, United States
g Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
h Department of Medicine, Washington University, Saint Louis, MO, United States
i Alvin J Siteman Cancer Center, Washington University, Saint Louis, MO, United States


Abstract
Purpose: This study aims to develop a constrained local arterial input function (cL-AIF) to improve quantitative analysis of dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) data by accounting for the contrast-agent bolus amplitude error in the voxel-specific AIF. Procedures: Bayesian probability theory-based parameter estimation and model selection were used to compare tracer kinetic modeling employing either the measured remote-AIF (R-AIF, i.e., the traditional approach) or an inferred cL-AIF against both in silico DCE-MRI data and clinical, cervical cancer DCE-MRI data. Results: When the data model included the cL-AIF, tracer kinetic parameters were correctly estimated from in silico data under contrast-to-noise conditions typical of clinical DCE-MRI experiments. Considering the clinical cervical cancer data, Bayesian model selection was performed for all tumor voxels of the 16 patients (35,602 voxels in total). Among those voxels, a tracer kinetic model that employed the voxel-specific cL-AIF was preferred (i.e., had a higher posterior probability) in 80 % of the voxels compared to the direct use of a single R-AIF. Maps of spatial variation in voxel-specific AIF bolus amplitude and arrival time for heterogeneous tissues, such as cervical cancer, are accessible with the cL-AIF approach. Conclusions: The cL-AIF method, which estimates unique local-AIF amplitude and arrival time for each voxel within the tissue of interest, provides better modeling of DCE-MRI data than the use of a single, measured R-AIF. The Bayesian-based data analysis described herein affords estimates of uncertainties for each model parameter, via posterior probability density functions, and voxel-wise comparison across methods/models, via model selection in data modeling. © 2017 World Molecular Imaging Society


Document Type: Article in Press
Source: Scopus


12) 

Saha, D., Sun, W., Li, C., Nizampatnam, S., Padovano, W., Chen, Z., Chen, A., Altan, E., Lo, R., Barbour, D.L., Raman, B.
Engaging and disengaging recurrent inhibition coincides with sensing and unsensing of a sensory stimulus
(2017) Nature Communications, 8, art. no. 15413, . 

DOI: 10.1038/ncomms15413


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


Abstract
Even simple sensory stimuli evoke neural responses that are dynamic and complex. Are the temporally patterned neural activities important for controlling the behavioral output? Here, we investigated this issue. Our results reveal that in the insect antennal lobe, due to circuit interactions, distinct neural ensembles are activated during and immediately following the termination of every odorant. Such non-overlapping response patterns are not observed even when the stimulus intensity or identities were changed. In addition, we find that ON and OFF ensemble neural activities differ in their ability to recruit recurrent inhibition, entrain field-potential oscillations and more importantly in their relevance to behaviour (initiate versus reset conditioned responses). Notably, we find that a strikingly similar strategy is also used for encoding sound onsets and offsets in the marmoset auditory cortex. In sum, our results suggest a general approach where recurrent inhibition is associated with stimulus 'recognition' and 'derecognition'. © The Author(s) 2017.


Document Type: Article
Source: Scopus


13) 

Jaeger, A.a , Dobbins, I.G.b 
Revising recognition judgments during noisy recognition evidence accumulation: The dynamics of losses versus gains
(2017) Memory and Cognition, pp. 1-15. Article in Press. 

DOI: 10.3758/s13421-017-0715-2


a Department of Psychology, Federal University of Minas Gerais, Antonio Carlos Avenue, 6627, Belo Horizonte, MG, Brazil
b Department of Psychology, Washington University, St. Louis, MO, United States


Abstract
Outside the laboratory, we sometimes revise our recognition judgments of others—realizing, for example, that we have accidentally failed to greet an acquaintance we just passed in the hallway. These recognition reversals have rarely been studied. Here, using a basic noisy-accumulation framework, we simulated recognition response reversals in which initial speeded recognition judgments were followed by an opportunity to revise the initial judgment. The simulation predictions were compared to empirical data from two experiments in which we gave participants the opportunity to revise each of their initial speeded recognition judgments. The speeded old–new responses were restricted to either 300–800 ms (Exp. 1) or 200–600 ms (Exp. 2) after each probe’s onset, and the second response was self-paced in both experiments. The noisy-accumulation framework correctly anticipated three findings. First, gain rates (incorrect followed by correct responses) always exceeded loss rates (correct followed by incorrect responses). Second, despite being corrective, the raw gain rates exhibited a modest negative correlation with overall recognition skill. Third, when gain rates were conditioned on the opportunity to correct an initial error (conditional gain rate), they were then positively correlated with recognition skill but were less diagnostic than the conditional loss rates. Thus, the mechanics of noisy accumulation naturally predict that skilled recognizers will demonstrate infrequent corrective behavior but a high probability of correction, should an initial error occur. © 2017 Psychonomic Society, Inc.


Author Keywords
Accumulation;  Memory;  Recognition;  Simulation


Document Type: Article in Press
Source: Scopus


14) 

Nemanich, S.T.a , McNeely, M.E.a b , Earhart, G.M.a b c , Norris, S.A.b , Black, K.J.b c d e 
A case of apparent upper-body freezing in parkinsonism while using a wheelchair
(2017) Frontiers in Neurology, 8 (MAY), art. no. 205, . 

DOI: 10.3389/fneur.2017.00205


a Program in Physical Therapy, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
d Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
e Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, United States


Abstract
Freezing of gait (FOG) is a common, disabling gait disturbance in Parkinson's disease (PD) and other Parkinsonian syndromes. Freezing also occurs during non-gait movements involving the upper limbs. The mechanisms underlying freezing are complex, likely involving motor, cognitive, and sensory systems that contribute to the episodes. Here, we reported a 60-year-old female with a 24-year history of parkinsonism who experienced significant FOG when ambulatory. Disease progression resulted in her permanent use of a powered wheelchair. While using the power chair, the patient experiences apparent paroxysmal freezing in the hand and arm used to steer and propel the chair. These episodes, some lasting up to several minutes, occur only in circumstances (e.g., entering and leaving an elevator) that are similar to environments known to elicit and exacerbate FOG. Episodes are transient and can be volitionally interrupted by the patient but sometimes require external assistance. Therapeutic intervention for this type of potential freezing has yet to be determined. This case may provide insight into the complex nature of freezing behavior and suggests a need for new approaches to treating non-traditional freezing behavior. © 2017 Nemanich, McNeely, Earhart, Norris and Black.


Author Keywords
Akinesia;  Freezing;  Hypokinesia;  Parkinson's disease;  Upper-limb freezing


Document Type: Article
Source: Scopus


15) 

Richardson, S.P.a , Altenmüller, E.b , Alter, K.c , Alterman, R.L.d , Chen, R.e , Frucht, S.f , Furuya, S.g , Jankovic, J.h , Jinnah, H.A.i j k , Kimberley, T.J.l , Lungu, C.m , Perlmutter, J.S.n o p q r , Prudente, C.N.l , Hallett, M.s 
Research priorities in limb and task-specific dystonias
(2017) Frontiers in Neurology, 8 (MAY), art. no. 170, . 

DOI: 10.3389/fneur.2017.00170


a Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM, United States
b Institute for Music Physiology and Musicians' Medicine (IMMM), Hannover University of Music, Drama and Media, Hannover, Germany
c Functional and Applied Biomechanics Section, Rehabilitation Medicine, National Institute of Child Health and Development, National Institutes of Health, Bethesda, MD, United States
d Division of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, United States
e Division of Neurology, Department of Medicine (Neurology), Krembil Research Institute, University of Toronto, Toronto, ON, Canada
f Robert and John M. Bendheim Parkinson and Movement Disorders Center, Mount Sinai Hospital, New York, NY, United States
g Musical Skill and Injury Center (MuSIC), Sophia University, Tokyo, Japan
h Department of Neurology, Baylor College of Medicine, Houston, TX, United States
i Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
j Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, United States
k Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States
l Department of Rehabilitation Medicine, Division of Physical Therapy and Rehabilitation Science, University of Minnesota, Minneapolis, MN, United States
m Division of Clinical Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
n Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
o Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
p Department of Neurosciences, Washington University School of Medicine, St. Louis, MO, United States
q Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
r Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
s Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States


Abstract
Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer's cramp, runner's dystonia, or musician's dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of diagnostic criteria for limb dystonia, more precise phenotypic characterization and innovative clinical trial design that considers clinical heterogeneity, and limited available number of participants. © 2017 Pirio Richardson, Altenmüller, Alter, Alterman, Chen, Frucht, Furuya, Jankovic, Jinnah, Kimberley, Lungu, Perlmutter, Prudente and Hallett.


Author Keywords
Botulinum toxin;  Deep brain stimulation;  Dystonia;  Inhibition;  Limb;  Research priorities;  Task-specific


Document Type: Review
Source: Scopus


16) 

Kallogjeri, D.a c , Piccirillo, J.F.a , Spitznagel, E., Jr.b , Hale, S.c , Nicklaus, J.E.d , Hardin, F.M.e , Shimony, J.S.f , Coalson, R.S.f g , Schlaggar, B.L.f g h i j 
Cognitive training for adults with bothersome tinnitus a randomized clinical trial
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (5), pp. 443-451. 

DOI: 10.1001/jamaoto.2016.3779


a Department of Otolaryngology-Head and Neck Surgery, Washington University, School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, United States
b Department of Mathematics, Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
d AbbVie Clinical Pharmacology Research Unit, Global Pharmaceutical R and D, Grayslake, IL, United States
e Case Western Reserve University, School of Medicine, Cleveland, OH, United States
f Mallinckrodt Institute of Radiology, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
g Department of Neurology, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
h Department of Pediatrics, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
i Department of Neuroscience, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
j Department of Psychiatry, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States


Abstract
IMPORTANCE: Individuals with tinnitus have poorer working memory, slower processing speeds and reaction times, and deficiencies in selective attention, all of which interfere with readiness and performance. Brain Fitness Program-Tinnitus (BFP-T) is a cognitive training program specially designed to exploit neuroplasticity for preservation and expansion of cognitive health in adults with tinnitus. OBJECTIVE: To evaluate the effect of the BFP-T on tinnitus. DESIGN, SETTING, AND PARTICIPANTS: This open-label, intention-to-treat randomized clinical trial prescreened 191 patients with tinnitus and 64 healthy controls (HCs) from June 1, 2012, through October 31, 2013. Participants were 40 adults with bothersome tinnitus for more than 6 months and 20 age-matched HCs. Patients with tinnitus were randomized to a BFP-T or non-BFP-T control group. The BFP-T was completed online, and assessments were completed at Washington University School of Medicine. INTERVENTIONS: Participants in the intervention group were required to complete the BFP-T online 1 hour per day 5 days per week for 8 weeks. Tinnitus assessment, neuroimaging, and cognitive testing were completed at baseline and 8 weeks later. The HCs underwent neuroimaging and cognitive assessments. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the change in Tinnitus Handicap Inventory (THI) score. Behavioral measures, neuroimaging, and cognitive tests were performed before and after the intervention. RESULTS: A total of 40 patients with tinnitus and 20 HCs participated in the study (median [range] age, 56 [35-64] years in the BFP-T group, 52 [24-64] years in the non-BFP-T group, and 50 [30-64] years in the HC group; 13 [65%] in the BFP-T group, 14 [70%] in the non-BFP-T group, and 13 [65%] in the HC group were males; and 16 [80%] in the BFP-T group, 16 [80%] in the non-BFP-T group, and 15 [75%] in the HC group were white). There was a reduction in the THI score in the BFP-T group (median, 7; range,-16 to 64) and non-BFP-T group (median, 11; range, -6 to 26), but this reduction was not significantly different between the 2 groups (median difference, 0; 95% CI, -10 to 8). There was no difference in cognitive test scores and other behavioral measures. There was a significant difference between baseline and follow-up in functional connectivity in cognitive control regions in the BFP-T group but not in HCs or individuals with untreated tinnitus. Of the 20 patients in the BFP-T group, 10(50%) self-reported improvement attributable to the intervention, and 6 (30%) reported to be much improved in the domains of tinnitus, memory, attention, and concentration. CONCLUSIONS AND RELEVANCE: These findings suggest that the computer-based cognitive training program is associated with self-reported changes in attention, memory, and perception of tinnitus. A possible mechanistic explanation for these changes could be neuroplastic changes in key brain systems involved in cognitive control. Cognitive training programs might have a role in the future treatment of patients with tinnitus. © 2017 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus


17) 

Huff, J.S.a , Naunheim, R.b , Ghosh Dastidar, S.c , Bazarian, J.d , Michelson, E.A.e 
Referrals for CT scans in mild TBI patients can be aided by the use of a brain electrical activity biomarker
(2017) American Journal of Emergency Medicine, . Article in Press. 

DOI: 10.1016/j.ajem.2017.05.027


a University of Virginia Health System, Charlottesville, VA, United States
b Washington University Barnes Jewish Medical Center, St. Louis, MO, United States
c BrainScope Company, Inc., Bethesda, MD, United States
d University of Rochester Medical Center, Rochester, NY, United States
e Department of Emergency Medicine, Texas Tech Univ. Health Sciences Center, El Paso, TX, United States


Author Keywords
Brain function;  Classification;  CT;  EEG Biomarker;  MTBI


Document Type: Article in Press
Source: Scopus


18) 

Pearson, T.S.b g , Pons, R.b h , Engelstad, K.a , Kane, S.A.c , Goldberg, M.E.d e f i j , De Vivo, D.C.a 
Paroxysmal eye-head movements in Glut1 deficiency syndrome
(2017) Neurology, 88 (17), pp. 1666-1673. 

DOI: 10.1212/WNL.0000000000003867


a Colleen Giblin Research Laboratory, United States
b Division of Pediatric Neurology, Department of Neurology, United States
c Department of Ophthalmology, Edward S. Harkness Eye Institute, United States
d Mahoney-Keck Center for Brain and Behavior Research, United States
e Department of Neuroscience, United States
f Department of Neurology, Psychiatry, and Ophthalmology, Columbia University, CPS, New York, NY, United States
g Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
h First Department of Pediatrics, National and Kapodistrian University of Athens, Aghia Sofia Hospital, Greece
i Kavli Institute for Neuroscience, Columbia University, United States
j Division of Neurobiology and Behavior, New York State Psychiatric Institute, New York, United States


Abstract
Objective: To describe a characteristic paroxysmal eye-head movement disorder that occurs in infants with Glut1 deficiency syndrome (Glut1 DS). Methods: We retrospectively reviewed the medical charts of 101 patients with Glut1 DS to obtain clinical data about episodic abnormal eye movements and analyzed video recordings of 18 eye movement episodes from 10 patients. Results: A documented history of paroxysmal abnormal eye movements was found in 32/101 patients (32%), and a detailed description was available in 18 patients, presented here. Episodes started before age 6 months in 15/18 patients (83%), and preceded the onset of seiz ures in10/16 patients (63%) who experienced both types of episodes. Eye movement episodes resolved, with or without treatment, by 6 years of age in 7/8 patients with documented longtermcourse. Episodes were brief (usually ,5 minutes). Video analysis revealed that the eye movements were rapid, multidirectional, and often accompanied by a head movement in the same direction. Eye movements were separated by clear intervals of fixation, usually ranging from 200to 800 ms. The movements were consistent with eye-head gaze saccades. These movements can be distinguished from opsoclonus by the presence of a clear intermovement fixation interval and the association of a same-direction head movement. Conclusions: Paroxysmal eye-head movements, for which we suggest the term aberrant gaze saccades, are an early symptom of Glut1 DS in infancy. Recognition of the episodes will facilitate prompt diagnosis of this treatable neurodevelopmental disorder. © 2017 American Academy of Neurology.


Document Type: Article
Source: Scopus


19) 

Lieu, J.E.C.
Role of qualitative research in shared decision making for treatment of sleep-disordered breathing: Patients, preferences, and personal factors
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (3), pp. 213-214. 

DOI: 10.1001/jamaoto.2016.3364


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


Document Type: Short Survey
Source: Scopus

https://www.scopus.com/static/images/s.gif


20) 

Zipfel, G.J.
Dural arteriovenous fistula: A clinical model of thalamic dementia?: Response
(2017) Journal of Neurosurgery, 126 (3), p. 1022. 

DOI: 10.3171/2016.7.JNS161826


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


Document Type: Letter
Source: Scopus


21) 

Liang, X., Holy, T.E., Taghert, P.H.
A Series of Suppressive Signals within the Drosophila Circadian Neural Circuit Generates Sequential Daily Outputs
(2017) Neuron, . Article in Press. 

DOI: 10.1016/j.neuron.2017.05.007


Department of Neuroscience, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA


Abstract
We studied the Drosophila circadian neural circuit using whole-brain imaging in vivo. Five major groups of pacemaker neurons display synchronized molecular clocks, yet each exhibits a distinct phase of daily Ca2+ activation. Light and neuropeptide pigment dispersing factor (PDF) from morning cells (s-LNv) together delay the phase of the evening (LNd) group by 
12 hr; PDF alone delays the phase of the DN3 group by 17 hr. Neuropeptide sNPF, released from s-LNv and LNd pacemakers, produces Ca2+ activation in the DN1 group late in the night. The circuit also features negative feedback by PDF to truncate the s-LNv Ca2+ wave and terminate PDF release. Both PDF and sNPF suppress basal Ca2+ levels in target pacemakers with long durations by cell-autonomous actions. Thus, light and neuropeptides act dynamically at distinct hubs of the circuit to produce multiple suppressive events that create the proper tempo and sequence of circadian pacemaker neuronal activities. Liang et al. record 24-hr Ca2+ activity patterns in all the major circadian pacemaker neurons of the Drosophila brain in vivo. Their results reveal a series of suppressive signals that creates a dynamic and patterned sequence of temporal outputs. © 2017 Elsevier Inc.


Author Keywords
Calcium;  Circadian physiology;  Drosophila;  Modulation;  Neuropeptide


Document Type: Article in Press
Source: Scopus


22) 

Hayes, J.F.a , Eichen, D.M.b , Barch, D.M.a , Wilfley, D.E.a 
Executive function in childhood obesity: Promising intervention strategies to optimize treatment outcomes
(2017) Appetite, . Article in Press. 

DOI: 10.1016/j.appet.2017.05.040


a Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, United States
b University of California, San Diego, 9500 Gilman Drive #0874, La Jolla, CA 92093, United States


Abstract
Executive functions (EFs) are hypothesized to play a role in the development and maintenance of obesity due to their role in self-regulatory processes that manage energy-balance behaviors. Children with obesity have well-documented deficits in EF, which may impede effectiveness of current, evidence-based treatments. This review examines top-down EF processes (e.g., inhibitory control, working memory, cognitive flexibility), as well as bottom-up automatic processes that interact with EFs (e.g., attentional bias, delay discounting) and their relation to weight-loss treatment success in children. It then evaluates EF-related interventions that may improve treatment response. Empirical studies that included an intervention purported to affect EF processes as well as pre-post measurements of EF and/or relative weight in populations ages 19 or younger with overweight/obesity were reviewed. Findings indicate that poorer EF may hinder treatment response. Moreover, there is preliminary evidence that behavioral weight loss intervention and physical activity may positively affect EF and that improvements in EF are related to enhanced weight loss. Finally, novel intervention strategies, such as computer training of core EFs, attention modification programs, and episodic future thinking, show promise in influencing both EFs and EF-related skills and weight. Further research is needed to provide more conclusive evidence of the efficacy of these interventions and additional applications and settings should be considered. © 2017 Elsevier Ltd.


Document Type: Article in Press
Source: Scopus


23) 

Lu, P.G.a , Kung, N.H.b , Van Stavern, G.P.b 
Ethambutol optic neuropathy associated with enhancement at the optic chiasm
(2017) Canadian Journal of Ophthalmology, . Article in Press. 

DOI: 10.1016/j.jcjo.2017.03.001


a Washington University School of Medicine, St. Louis, Missouri
b Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri


Document Type: Article in Press
Source: Scopus


24) 

Sadler, B.E.a , Grant, J.D.a , Duncan, A.E.a b , Sartor, C.E.c , Waldron, M.d , Heath, A.C.a , Bucholz, K.K.a 
The influence of paternal separation, paternal history of alcohol use disorder risk, and early substance use on offspring educational attainment by young adulthood
(2017) Journal of Studies on Alcohol and Drugs, 78 (3), pp. 426-434. 

DOI: 10.15288/jsad.2017.78.426


a Washington University School of Medicine, St. Louis, MO, United States
b George Warren Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
c Yale School of Medicine, New Haven, CT, United States
d Indiana University Bloomington, Bloomington, IN, United States


Abstract
Objective: This study aimed to determine the associations among paternal alcohol problems, separation, and educational attainment in European American and African American offspring and whether offspring early alcohol/tobacco/marijuana use influenced these associations. Method: Families with offspring ages 13–19 years at intake were selected from state birth records and screened by telephone to determine high-risk or low-risk status (with/without paternal heavy drinking). Families of men with two or more driving-under-the-influence offenses were added as a very-high-risk group. Data from 340 African American and 288 European American offspring who were not enrolled in school at their last interview were analyzed. Educational attainment was modeled as less than high school, high school only (reference category), and some college or higher. Separation was defined as offspring report of not having lived continuously in the same household with their biological father from birth to age 14. Analyses were stratified by race. Results: In European Americans, neither family risk status nor early alcohol/ tobacco/marijuana use was associated with educational outcomes. However, paternal separation significantly elevated the likelihood of not completing high school in all models (relative risk ratios [RRRs] = 6.0–8.1, p <.001). For African American offspring, likelihoods of high school noncompletion were elevated marginally for paternal separation in only one model, but significantly for early marijuana use (RRRs = 2.8–3.2, p <.05). Very-high-risk status significantly reduced the likelihood of post–high school education in an adjusted model (RRR = 0.4, p <.05). Conclusions: High school noncompletion was significantly associated with paternal separation in European Americans and with early marijuana use in African American offspring. In addition, very-high-risk status reduced the likelihood of post–high school education in African American offspring only, suggesting that research with ethnically diverse samples yields important differences when examining outcomes of both separation and substance use on offspring education. © 2017, Alcohol Research Documentation Inc. All rights reserved.


Document Type: Article
Source: Scopus


25) 

Avidan, M.S.a , Maybrier, H.R.a , Abdallah, A.B.a , Jacobsohn, E.b , Vlisides, P.E.d , Pryor, K.O.e , Veselis, R.A.f , Grocott, H.P.c , Emmert, D.A.a , Rogers, E.M.e , Downey, R.J.g , Yulico, H.h , Noh, G.-J.i , Lee, Y.H.i , Waszynski, C.M.j , Arya, V.K.k , Pagel, P.S.l , Hudetz, J.A.l , Muench, M.R.a , Fritz, B.A.a , Waberski, W.m , Inouye, S.K.n , Mashour, G.A.d 
Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: An international, multicentre, double-blind, randomised clinical trial
(2017) The Lancet, . Article in Press. 

DOI: 10.1016/S0140-6736(17)31467-8


a Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA
b Department of Anesthesiology and Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
c Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, MB, Canada
d Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA
e Department of Anesthesiology, Weill Cornell Medicine, New York City, NY, US
f Department of Neuroanesthesiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA
g Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, NY, USA
h Department of Anesthesiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA
i Department of Anesthesiology, Asan Medical Center, Seoul, South Korea
j Department of Medicine, Hartford Hospital, Hartford, CT, USA
k Department of Anaesthesiology and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
l Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA
m Department of Anesthesiology, Hartford Hospital, Hartford, Connecticut, USA
n Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, and Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA


Abstract
Background: Delirium is a common and serious postoperative complication. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia, and some evidence suggests that ketamine prevents delirium. The primary purpose of this trial was to assess the effectiveness of ketamine for prevention of postoperative delirium in older adults. Methods: The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] study is a multicentre, international randomised trial that enrolled adults older than 60 years undergoing major cardiac and non-cardiac surgery under general anaesthesia. Using a computer-generated randomisation sequence we randomly assigned patients to one of three groups in blocks of 15 to receive placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision. Participants, clinicians, and investigators were blinded to group assignment. Delirium was assessed twice daily in the first 3 postoperative days using the Confusion Assessment Method. We did analyses by intention-to-treat and assessed adverse events. This trial is registered with clinicaltrials.gov, number NCT01690988. Findings: Between Feb 6, 2014, and June 26, 2016, 1360 patients were assessed, and 672 were randomly assigned, with 222 in the placebo group, 227 in the 0·5 mg/kg ketamine group, and 223 in the 1·0 mg/kg ketamine group. There was no difference in delirium incidence between patients in the combined ketamine groups and the placebo group (19·45% vs 19·82%, respectively; absolute difference 0·36%, 95% CI -6·07 to 7·38, p=0·92). There were more postoperative hallucinations (p=0·01) and nightmares (p=0·03) with increasing ketamine doses compared with placebo. Adverse events (cardiovascular, renal, infectious, gastrointestinal, and bleeding), whether viewed individually (p value for each >0·40) or collectively (36·9% in placebo, 39·6% in 0·5 mg/kg ketamine, and 40·8% in 1·0 mg/kg ketamine groups, p=0·69), did not differ significantly across groups. Interpretation: A single subanaesthetic dose of ketamine did not decrease delirium in older adults after major surgery, and might cause harm by inducing negative experiences. Funding: National Institutes of Health and Cancer Center Support. © 2017 Elsevier Ltd.


Document Type: Article in Press
Source: Scopus


26) 

Stein, L.R.a , Zorumski, C.F.a b c , Izumi, Y.a b c 
Hippocampal slice preparation in rats acutely suppresses immunoreactivity of microtubule-associated protein (Map2) and glycogen levels without affecting numbers of glia or levels of the glutamate transporter VGlut1
(2017) Brain and Behavior, . Article in Press. 

DOI: 10.1002/brb3.736


a Department of Psychiatry Washington University School of Medicine St. Louis, MO USA
b The Taylor Family Institute for Innovative Psychiatric Research Washington University School of Medicine St. Louis, MO USA
c Center for Brain Research in Mood Disorders Washington University School of Medicine St. Louis, MO USA


Abstract
Introduction: With its preservation of cytoarchitecture and synaptic circuitry, the hippocampal slice preparation has been a critical tool for studying the electrophysiological effects of pharmacological and genetic manipulations. To analyze the maximum number of slices or readouts per dissection, long incubation times postslice preparation are commonly used. We were interested in how slice integrity is affected by incubation postslice preparation. Methods: Hippocampal slices were prepared by three different methods: a chopper, a vibratome, and a rotary slicer. To test slice integrity, we compared glycogen levels and immunohistochemistry of selected proteins in rat hippocampal slices immediately after dissection and following 2 and 4 hr of incubation. Results: We found that immunoreactivity of the dendritic marker microtubule-associated protein 2 (Map2) drastically decreased during this incubation period, whereas immunoreactivity of the glutamate transporter VGlut1 did not significantly change with incubation time. Astrocytic and microglial cell numbers also did not significantly change with incubation time whereas glycogen levels markedly increased during incubation. Conclusion: Immunoreactivity of the dendritic marker Map2 quickly decreased after dissection with all the slicing methods. This work highlights a need for caution when using long incubation periods following slice preparation. © 2017 Published by Wiley Periodicals, Inc.


Author Keywords
Glycogen;  Hippocampus;  Map2;  Slice preparation;  VGlut1


Document Type: Article in Press
Source: Scopus


27) 

Bahr, N.C.a , Trotman, R.L.b , Samman, H.c , Jung, R.S.d , Rosterman, L.R.c , Weil, G.J.e , Hinthorn, D.R.a 
Eosinophilic meningitis due to infection with Paragonimus kellicotti
(2017) Clinical Infectious Diseases, 64 (9), pp. 1271-1274. 

DOI: 10.1093/cid/cix102


a Division of Infectious Diseases, Department of Medicine, University of Kansas, MS 1028, 3901 Rainbow Blvd, Kansas City, KS, United States
b Infectious Diseases Specialty Clinic, CoxHealth, Springfield, MO, United States
c Department of Neurology, University of Kansas, Kansas City, United States
d Vascular Neurology and Neurointerventional Surgery, CoxHealth, Springfield, United States
e Infectious Diseases Division, Department of Medicine, Washington University School of Medicine, St Louis, MO, United States


Abstract
Paragonimus kellicotti is an emerging pathogen in the United States with 19 previously reported cases, most in Missouri. Pulmonary symptoms with eosinophilia are most common, though 1 case did involve the central nervous system with few symptoms. We describe the first 2 cases of eosinophilic meningitis due to Paragonimus kellicotti. © The Author 2017.


Author Keywords
Eosinophilia;  Meningitis;  Paragonimus;  Trematoda


Document Type: Article
Source: Scopus


28) 

Wolf, T.J.a , Spiers, M.J.a , Doherty, M.b , Leary, E.V.c 
The effect of self-management education following mild stroke: An exploratory randomized controlled trial*
(2017) Topics in Stroke Rehabilitation, 24 (5), pp. 345-352. 

DOI: 10.1080/10749357.2017.1289687


a Department of Occupational Therapy, University of Missouri, Columbia, MO, United States
b Washington University in St. Louis, St. Louis, MO, United States
c Biostatistics and Research Design Unit, School of Medicine, University of Missouri, Columbia, MO, United States


Abstract
Background: Mild stroke comprises 53% of stroke hospital admissions; however, the majority of those with mild stroke patients receive little support to address chronic symptoms following stroke. Objectives: To evaluate the feasibility and preliminary effect of the Chronic Disease Self-Management Program (CDSMP) for use with individuals immediately post mild-stroke. Methods: Single-blind, exploratory, randomized controlled trial with participants who sustained a mild stroke (NIHSS <6). Participants were randomized to either receive the CDSMP intervention or to an inactive control group. Primary outcomes were self-reported health and self-efficacy and were obtained at baseline, post-intervention (treatment group only), and at six months post-baseline. Wilcoxon Signed Rank Tests were used to compare change score differences for all participants and effect size was computed using effect size r for non-parametric data. Results: There were no differences between groups in demographics or baseline data with the exception of how participants felt they are able to manage their health in general (p = 0.05). At follow-up, effect sizes ranged from 0 to 0.35 (no effect to medium effect); however, while the treatment group reported improvements in several areas of health at follow-up, the results are not compelling when compared to the control group over the same time period. Conclusions: The results did not identify a positive effect that would support the use of the CDSMP with individual’s post-mild stroke; however, the generalizability of these results is limited secondary to several limitations in this exploratory study. © 2017 Informa UK Limited, trading as Taylor & Francis Group.


Author Keywords
Chronic disease;  Occupational therapy;  Rehabilitation;  Stroke;  Stroke management


Document Type: Article
Source: Scopus


29) 

Schuckit, M.A.a , Smith, T.L.a , Danko, G.a , Anthenelli, R.a , Schoen, L.a , Kawamura, M.a , Kramer, J.b , Dick, D.M.c , Neale, Z.d , Kuperman, S.e , Mccutcheon, V.f , Anokhin, A.P.g , Hesselbrock, V.h , Hesselbrock, M.i , Bucholz, K.g 
A Prospective Comparison of How the Level of Response to Alcohol and Impulsivity Relate to Future DSM-IV Alcohol Problems in the COGA Youth Panel
(2017) Alcoholism: Clinical and Experimental Research, . Article in Press. 

DOI: 10.1111/acer.13407


a Department of Psychiatry University of California, San Diego La Jolla, California
b Department of Psychiatry The University of Iowa Iowa City, Iowa
c Department of Psychiatry Virginia Commonwealth University Richmond, Virginia
d Department of Psychology Virginia Commonwealth University Richmond, Virginia
e Child Psychiatry Clinic The University of Iowa Iowa City, Iowa
f Department of Psychiatry Washington University St. Louis Missouri
g Washington University in Saint Louis School of Medicine St. Louis, Missouri
h Department of Psychiatry University of Connecticut Farmington, Connecticut
i Department of PsychiatrySchool of Medicine University of Connecticut Farmington, Connecticut


Abstract
Background: Alcohol problems reflect both environmental and genetic characteristics that often operate through endophenotypes like low levels of response (low LRs) to alcohol and higher impulsivity. Relationships of these preexisting characteristics to alcohol problems have been studied, but few analyses have included both low LR and impulsivity in the same model. Methods: We extracted prospective data from 1,028 participants in the Prospective Youth Sample of the Collaborative Study on the Genetics of Alcoholism (COGA). At Time 1 (age 18), these drinking but non-alcohol-dependent males and females completed the Barratt Impulsivity Scale and the Self-Report of the Effects of Alcohol questionnaire regarding drinks required for effects the first 5 times of drinking (SRE5-LR). Two years later, they reported perceived drinking patterns of peers (PEER), their own alcohol expectancies (EXPECT), and their drinking to cope with stress (COPE). Subsequently, at Time 3, participants reported numbers of up to 11 DSM-IV alcohol criterion items experienced in the 2 years since Time 2 (ALC PROBS). Data were analyzed using structural equation modeling (SEM). Results: In the SEM, Baseline SRE5-LR and impulsivity were weakly related and did not interact in predicting later ALC PROBS. LR was directly linked to Time 3 ALC PROBS and to PEER, but had no direct path to EXPECT, with partial mediation to ALC PROBS through PEER to EXPECT and via COPE. Impulsivity did not relate directly to ALC PROBS or PEER, but was directly related to EXPECT and COPE, with effects on ALC PROBS also operating through EXPECT and COPE. Conclusions: Low LRs and impulsivity related to Time 3 ALC PROBS through somewhat different paths. Education- and counseling-based approaches to mitigate future alcohol problems may benefit from emphasizing different potential mediators of adverse alcohol outcomes for youth with low LRs versus those with high impulsivity or both characteristics. © 2017 Research Society on Alcoholism.


Author Keywords
Alcohol Problems;  Impulsivity;  Levels of Response to Alcohol;  Structural Equation Models


Document Type: Article in Press
Source: Scopus


30) 

Franco, M.J., Phillips, B.Z., Lalchandani, G.R., Mackinnon, S.E.
Decompression of the superficial peroneal nerve: Clinical outcomes and anatomical study
(2017) Journal of Neurosurgery, 126 (1), pp. 330-335. 

DOI: 10.3171/2016.1.JNS152454


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


Abstract
OBJECTIVE: The authors of this study sought to determine the outcomes of patients undergoing superficial peroneal nerve (SPN) release to treat lower-extremity pain and describe consistent anatomical landmarks to direct surgical planning. METHODS: This retrospective cohort study examined 54 patients with pain in the SPN distribution who were treated with decompression between 2011 and 2014. Patients rated pain and the effect of pain on quality of life (QOL) on the visual analog scale (VAS) from 0 to 10. Scores were then converted to percentages. Linear regression analysis was performed to assess the impact of the preoperative effect of pain on QOL, age, body mass index (BMI), and preoperative duration of pain on the postoperative effect of pain on QOL. Measurements were made intraoperatively in 13 patients to determine the landmarks for identifying the SPN. RESULTS A higher BMI was a negative predictor for improvement in the effect of pain on QOL. A decrease in pain compared with the initial level of pain suggested a nonlinear relationship between these variables. A minority of patients (7 of 16) with a preoperative pain VAS score ≤ 60 reported less pain after surgery. A large majority (30 of 36 patients) of those with a preoperative pain VAS score > 60 reported improvement. Intraoperative measurements demonstrated that the SPN was consistently found to be 5 ± 1.1, 5 ± 1.1, and 6 ± 1.2 cm lateral to the tibia at 10, 15, and 20 cm proximal to the lateral malleolus, respectively. CONCLUSIONS: A majority of patients with a preoperative pain VAS score > 60 showed a decrease in postoperative pain. A higher BMI was associated with less improvement in the effect of pain on QOL. This information can be useful when counseling patients on treatment options. Based on the intraoperative data, the authors found that the SPN can be located at reliable points in reference to the tibia and lateral malleolus. ©AANS, 2017.


Author Keywords
Peripheral nerve compression;  Peripheral nerve pain;  Superficial peroneal nerve anatomy


Document Type: Article
Source: Scopus


31) 

Kennedy, R.E.a , Cutter, G.R.b , Wang, G.c , Schneider, L.S.d 
Challenging Assumptions About African American Participation in Alzheimer Disease Trials
(2016) American Journal of Geriatric Psychiatry, . Article in Press. 

DOI: 10.1016/j.jagp.2017.04.013


a Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
b Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL
c Department of Biostatistics, Washington University School of Medicine, St. Louis, MO
d Departments of Psychiatry, Neurology, and Gerontology, University of Southern California Keck School of Medicine, Los Angeles, CA


Abstract
Objective: The authors investigated potential effects of increased African American participation in Alzheimer disease (AD) and mild cognitive impairment (MCI) clinical trials by examining differences in comorbid conditions and treatment outcome affecting trial design. Methods: Using a meta-database of 18 studies from the Alzheimer's Disease Cooperative Study and the Alzheimer's Disease Neuroimaging Initiative, a cohort of 5,164 subjects were included for whom there were baseline demographic data and information on comorbid disorders, grouped by organ system. Meta-analysis was used to compare prevalence of comorbidities, dropouts, and rates of change on the cognitive subscale of the Alzheimer's Disease Assessment Scale by race. Clinical trial scenarios similar to recent therapeutic trials were simulated to determine effects of increased African American participation on statistical power. Results: Approximately 7% of AD, 4% of MCI, and 11% of normal participants were African American. African American subjects had higher prevalence of cardiovascular disorders (odds ratio: 2.10; 95% confidence interval [CI]: 1.71-2.57) and higher rate of dropouts (odds ratio: 1.60; 95% CI: 1.15-2.21) compared with whites but lower rates of other disorders. There were no significant differences in rate of progression (-0.862 points/year; 95% CI: -1.89 to 0.162) by race and little effect on power in simulated trials with sample sizes similar to current AD trial designs. Conclusion: Increasing African American participation in AD clinical trials will require adaptation of trial protocols to address comorbidities and dropouts. However, increased diversity is unlikely to negatively affect trial outcomes and should be encouraged to promote generalizability of trial results. © 2017 American Association for Geriatric Psychiatry.


Author Keywords
Alzheimer disease;  Clinical trial design;  Diversity;  Mild cognitive impairment;  Racial differences


Document Type: Article in Press
Source: Scopus

 

June 12, 2017

1) 

Hsu, W.-C.J.a b c , Wildburger, N.C.a d e l , Haidacher, S.J.g , Nenov, M.N.a h , Folorunso, O.a , Singh, A.K.a , Chesson, B.C.a , Franklin, W.F.d h i , Cortez, I.d h , Sadygov, R.G.b f , Dineley, K.T.h i j , Rudra, J.S.a , Taglialatela, G.h i , Lichti, C.F.a , Denner, L.f g h j , Laezza, F.a h j k 
PPARgamma agonists rescue increased phosphorylation of FGF14 at S226 in the Tg2576 mouse model of Alzheimer's disease
(2017) Experimental Neurology, 295, pp. 1-17. 

DOI: 10.1016/j.expneurol.2017.05.005


a Department of Pharmacology & Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
b Biochemistry and Molecular Biology Graduate Program, Graduate School of Biomedical Sciences, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
c M.D./Ph.D. Combined Degree Program, Graduate School of Biomedical Sciences, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
d Neuroscience Graduate Program, Graduate School of Biomedical Sciences, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
e Department of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO, United States
f Sealy Center for Molecular Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
g Department of Internal Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
h Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
i Department of Neurology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
j Center for Addiction Research, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
k Center for Biomedical Engineering, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, United States
l Department of Neurology, Washington University School of Medicine, 660 S Euclid Avenue, St. Louis, Missouri, United States


Abstract
Background Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal model of AD, RSG treatment rescued cognitive deficits and reduced aberrant activity of granule neurons in the dentate gyrus (DG), an area critical for memory formation. Methods We used a combination of mass spectrometry, confocal imaging, electrophysiology and split-luciferase assay and in vitro phosphorylation and Ingenuity Pathway Analysis. Results Using an unbiased, quantitative nano-LC-MS/MS screening, we searched for potential molecular targets of the RSG-dependent rescue of DG granule neurons. We found that S226 phosphorylation of fibroblast growth factor 14 (FGF14), an accessory protein of the voltage-gated Na+ (Nav) channels required for neuronal firing, was reduced in Tg2576 mice upon treatment with RSG. Using confocal microscopy, we confirmed that the Tg2576 condition decreased PanNav channels at the AIS of the DG, and that RSG treatment of Tg2576 mice reversed the reduction in PanNav channels. Analysis from previously published data sets identified correlative changes in action potential kinetics in RSG-treated T2576 compared to untreated and wildtype controls. In vitro phosphorylation and mass spectrometry confirmed that the multifunctional kinase GSK–3β, a downstream target of insulin signaling highly implicated in AD, phosphorylated FGF14 at S226. Assembly of the FGF14:Nav1.6 channel complex and functional regulation of Nav1.6-mediated currents by FGF14 was impaired by a phosphosilent S226A mutation. Bioinformatics pathway analysis of mass spectrometry and biochemistry data revealed a highly interconnected network encompassing PPARγ, FGF14, SCN8A (Nav 1.6), and the kinases GSK–3 β, casein kinase 2β, and ERK1/2. Conclusions These results identify FGF14 as a potential PPARγ-sensitive target controlling Aβ-induced dysfunctions of neuronal activity in the DG underlying memory loss in early AD. © 2017 Elsevier Inc.


Author Keywords
Alzheimer's disease;  Confocal microscopy;  Fibroblast growth factor 14;  Mass spectrometry;  PPARgamma


Document Type: Article
Source: Scopus

 

2) 

Agarwal, P.K.a , Finley, J.R.b , Rose, N.S.c , Roediger, H.L., IIIa 
Benefits from retrieval practice are greater for students with lower working memory capacity
(2017) Memory, 25 (6), pp. 764-771. 

DOI: 10.1080/09658211.2016.1220579


a Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychology, Fontbonne University, Clayton, MO, United States
c Department of Psychology, University of Notre Dame, Notre Dame, IN, United States


Abstract
We examined the effects of retrieval practice for students who varied in working memory capacity as a function of the lag between study of material and its initial test, whether or not feedback was given after the test, and the retention interval of the final test. We sought to determine whether a blend of these conditions exists that maximises benefits from retrieval practice for lower and higher working memory capacity students. College students learned general knowledge facts and then restudied the facts or were tested on them (with or without feedback) at lags of 0–9 intervening items. Final cued recall performance was better for tested items than for restudied items after both 10 minutes and 2 days, particularly for longer study–test lags. Furthermore, on the 2-day delayed test the benefits from retrieval practice with feedback were significantly greater for students with lower working memory capacity than for students with higher working memory capacity (r = −.42). Retrieval practice may be an especially effective learning strategy for lower ability students. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Author Keywords
feedback;  lag;  retrieval practice;  Testing effect;  working memory


Document Type: Article
Source: Scopus

 

3) 

Yang, Y.a e , Dickey, M.W.b c d , Fiez, J.b j , Murphy, B.e , Mitchell, T.f , Collinger, J.g h j k , Tyler-Kabara, E.h i , Boninger, M.g h j k l , Wang, W.g h j l m n 
Sensorimotor experience and verb-category mapping in human sensory, motor and parietal neurons
(2017) Cortex, 92, pp. 304-319. 

DOI: 10.1016/j.cortex.2017.04.021


a Department of Psychology, Carnegie Mellon University, Pittsburgh, PA, United States
b Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States
c Geriatric Research Education and Clinical Center, V.A. Pittsburgh Healthcare System, Pittsburgh, PA, United States
d Department of Communication Science and Disorders, University of Pittsburgh, Pittsburgh, PA, United States
e School of Electronics, Electrical Engineering and Computer Science, Queen's University, Belfast, United Kingdom
f Machine Learning Department, Carnegie Mellon University, Pittsburgh, PA, United States
g Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, United States
h Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States
i Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United States
j Center for the Neural Basis of Cognition, Pittsburgh, PA, United States
k Human Engineering Research Laboratories, Department of Veterans Affairs, Pittsburgh, PA, United States
l Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, United States
m Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
n Barnes-Jewish Hospital, St. Louis, MO, United States


Abstract
Semantic grounding is the process of relating meaning to symbols (e.g., words). It is the foundation for creating a representational symbolic system such as language. Semantic grounding for verb meaning is hypothesized to be achieved through two mechanisms: sensorimotor mapping, i.e., directly encoding the sensorimotor experiences the verb describes, and verb-category mapping, i.e., encoding the abstract category a verb belongs to. These two mechanisms were investigated by examining neuronal-level spike (i.e. neuronal action potential) activities from the motor, somatosensory and parietal areas in two human participants. Motor and a portion of somatosensory neurons were found to be involved in primarily sensorimotor mapping, while parietal and some somatosensory neurons were found to be involved in both sensorimotor and verb-category mapping. The time course of the spike activities and the selective tuning pattern of these neurons indicate that they belong to a large neural network used for semantic processing. This study is the first step towards understanding how words are processed by neurons. © 2017


Author Keywords
Action verbs;  Concept-to-concept mapping;  Experience-to-concept mapping;  Human neuron spikes;  Semantic grounding


Document Type: Article
Source: Scopus

 

4) 

Fewell, L.K.a , Levinson, C.A.b c , Stark, L.a 
Depression, worry, and psychosocial functioning predict eating disorder treatment outcomes in a residential and partial hospitalization setting
(2017) Eating and Weight Disorders, 22 (2), pp. 291-301. 

DOI: 10.1007/s40519-016-0357-6


a McCallum Place Eating Disorder Centers, 231 W. Lockwood Ave, St. Louis, MO, United States
b Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychological and Brain Sciences, University of Louisville, Louisville, KY, United States


Abstract
This retrospective study explores depression, worry, psychosocial functioning, and change in body mass index (BMI) as predictors of eating disorder (ED) symptomatology and BMI at discharge and 1-year follow-up from a residential and partial hospitalization ED treatment center. Participants were 423 male and female patients receiving treatment at an ED treatment center. Results indicate significant improvement in ED symptomatology, psychological impairment, and change in BMI (in patients with anorexia nervosa) at treatment discharge and follow-up compared to treatment admission (ps < 0.001). Depression and worry predicted ED symptomatology and psychological impairment at discharge (ps < 0.05). Depression, worry, and psychosocial functioning predicted ED symptomatology and psychological impairment at 1-year follow-up (ps < 0.001). Change in BMI was not a significant predictor of outcome. Depression, worry, and psychosocial functioning each play a role in treatment outcomes and may help clarify who might benefit from treatment. Clinicians in ED treatment centers should consider these as areas of focus for improved outcomes. © 2017, Springer International Publishing Switzerland.


Author Keywords
Anxiety;  Depression;  Eating disorder;  Predictor;  Treatment outcome;  Worry


Document Type: Article
Source: Scopus

 

5) 

Wei, X.a , Yu, J.W.a , Shattuck, P.b , Blackorby, J.a 
High School Math and Science Preparation and Postsecondary STEM Participation for Students with an Autism Spectrum Disorder
(2017) Focus on Autism and Other Developmental Disabilities, 32 (2), pp. 83-92. 

DOI: 10.1177/1088357615588489


a SRI International, 333 Ravenswood Avenue, Menlo Park, CA, United States
b Washington University, St Louis, MO, United States


Abstract
Previous studies suggest that individuals with an autism spectrum disorder (ASD) are more likely than other disability groups and the general population to gravitate toward science, technology, engineering, and mathematics (STEM) fields. However, the field knows little about which factors influence the STEM pipeline between high school and postsecondary STEM major. This study analyzed data from the National Longitudinal Transition Study-2, a nationally representative sample of students with an ASD in special education in the United States. Findings suggest that students with an ASD who took more classes in advanced math in a general education setting were more likely to declare a STEM major after controlling for background characteristics and previous achievement level. Educational policy implications are discussed. © Hammill Institute on Disabilities 2015.


Author Keywords
autism spectrum disorder;  college;  high school coursework;  postsecondary major;  science, technology, engineering, and mathematics (STEM);  standardized test scores


Document Type: Article
Source: Scopus

 

6) 

Beatrix, B.a , Katalin, H.b , Bernadette, P.c , Krisztina, D.b , Kerns, K.A.d , Sándor, R.e , Imre, T.f , János, K.g 
Security, reliance and availability: Psychometric features of the Kerns' security scale in Hungarian population
(2017) Mentalhigiene es Pszichoszomatika, 18 (2), pp. 171-193. 

DOI: 10.1556/0406.18.2017.008


a Department of Otorhinolaryngology, Clinical Centre, University of Pécs, Pécs, Hungary
b Department of Pediatrics, Clinical Center, University of Pécs, Pécs, Hungary
c Department of Developmental and Clinical Psychology, Faculty of Humanities, University of Pécs, Pécs, Hungary
d Department of Psychology, Kent State University, Kent, United States
e Department of Psychiatry, School of Medicine, Washington University, St. Louis, United States
f Department of Applied Psychology, Semmelweis University, Budapest, Hungary
g Institute of Behavioral Sciences, Medical School, University of Pécs, Szigeti út 12, Pécs, Hungary


Abstract
Background: This study examines the Kerns' Security Scale (KSS) that is a self-report questionnaire to assess school-age children's certain family-related experiences, and is widely used in the United States and in certain European countries. Objectives: The aim of the present investigation is to review the factor structure of the KSS in Hungarian population and to describe the characteristics of the scales in an Eastern-Central European country, as well as to check its external validity by the Child Depression Inventory, and to evaluate its feasibility in clinical practice and school psychology services. Methods: The sample consisted of 323 primary and secondary schools students (137 boys and 186 girls), aged 10-18 years. They completed the Kerns' Security Scale and the Child Depression Inventory. Results: statistical analysis has revealed that the items of the security questionnaire can be divided into three subscales, namely: Reliance, Availability, and Autonomy support. The mothers' subscale scores are higher than fathers' subscale scores (Reliance: t = 7.1, p < .001; Availability t = 8.9, p < .001; Autonomy support t = 3.2, p < .01). Conclusion: The results supported the three factor model of the KSS, and recommended to apply for clinical practice and in school psychology services. © 2017 Akadémiai Kiadó, Budapest.


Author Keywords
Attachment;  Autonomy support;  Depression;  Perceived security;  Preadolescence


Document Type: Review
Source: Scopus

 

7) 

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

DOI: 10.1007/s00701-017-3232-y


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


Document Type: Article in Press
Source: Scopus


8) 

Bundy, D.T., Souders, L., Baranyai, K., Leonard, L., Schalk, G., Coker, R., Moran, D.W., Huskey, T., Leuthardt, E.C.
Contralesional Brain–Computer Interface Control of a Powered Exoskeleton for Motor Recovery in Chronic Stroke Survivors
(2017) Stroke, . Article in Press. 

DOI: 10.1161/STROKEAHA.116.016304


From the Department of Rehabilitation Medicine, University of Kansas Medical Center, Kansas City (D.T.B.); Departments of Biomedical Engineering (D.T.B., R.C., D.W.M., E.C.L.), Neurology (L.S., K.B., L.L., T.H.), Neurological Surgery (E.C.L.), Mechanical Engineering and Material Sciences (E.C.L.), and Neuroscience (E.C.L.), Washington University, St. Louis, MO; and National Center for Adaptive Neurotechnologies, Wadsworth Center, NYS Department of Health, Albany, NY (G.S.).


Abstract
BACKGROUND AND PURPOSE—: There are few effective therapies to achieve functional recovery from motor-related disabilities affecting the upper limb after stroke. This feasibility study tested whether a powered exoskeleton driven by a brain–computer interface (BCI), using neural activity from the unaffected cortical hemisphere, could affect motor recovery in chronic hemiparetic stroke survivors. This novel system was designed and configured for a home-based setting to test the feasibility of BCI-driven neurorehabilitation in outpatient environments. METHODS—: Ten chronic hemiparetic stroke survivors with moderate-to-severe upper-limb motor impairment (mean Action Research Arm Test=13.4) used a powered exoskeleton that opened and closed the affected hand using spectral power from electroencephalographic signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. Patients used the system at home for 12 weeks. Motor function was evaluated before, during, and after the treatment. RESULTS—: Across patients, our BCI-driven approach resulted in a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in BCI control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved. CONCLUSIONS—: The findings demonstrate the therapeutic potential of a BCI-driven neurorehabilitation approach using the unaffected hemisphere in this uncontrolled sample of chronic stroke survivors. They also demonstrate that BCI-driven neurorehabilitation can be effectively delivered in the home environment, thus increasing the probability of future clinical translation. CLINICAL TRIAL REGISTRATION—: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02552368.Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. © 2017 American Heart Association, Inc.


Document Type: Article in Press
Source: Scopus

 

9) 

Qureshi, A.A., Parikh, R.P., Sharma, K., Myckatyn, T.M., Tenenbaum, M.M.
Nonsurgical Facial Rejuvenation: Outcomes and Safety of Neuromodulator and Soft-Tissue Filler Procedures Performed in a Resident Cosmetic Clinic
(2017) Aesthetic Plastic Surgery, pp. 1-7. Article in Press. 

DOI: 10.1007/s00266-017-0892-1


Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 1020 North Mason Rd., Suite 110, Building 3, St. Louis, MO, United States


Abstract
Background: The ability to perform nonsurgical facial rejuvenation procedures is a core competency requirement for plastic surgery residents. However, limited data exist on training models to achieve competency in nonsurgical facial rejuvenation and on outcomes of these procedures performed by residents. The purpose here is to evaluate patient-reported outcomes and safety of nonsurgical facial rejuvenation procedures performed by plastic surgery residents. Methods: We prospectively enrolled 50 patients undergoing neuromodulator and/or soft-tissue filler injections in a resident cosmetic clinic between April and August 2016. Patients completed FACE-Q modules pre-procedure, and at 1 week and 1 month post-procedure. Paired t-tests were used to calculate statistical significance of changes between pre- and post-procedure scores. Effect sizes were calculated to assess clinical improvement from pre- to post-procedure. The magnitude of change was interpreted using Cohen’s arbitrary criteria (small 0.20, moderate 0.50, large 0.80). Results: Forty-five patients completed the study. Patients experienced significant improvements (p < 0.001) in all FACE-Q domains, including aging appearance appraisal (improved from 49.7 ± 29.4 to 70.1 ± 21.6, effect size 0.79), psychological well-being (44.0 ± 14.6–78.6 ± 20.7, effect size 1.93), social functioning (48.6 ± 16.6–75.5 ± 21.7, effect size 1.20), and satisfaction with facial appearance (50.1 ± 13.7–66.2 ± 19.7, effect size 0.95). At 1 month, overall satisfaction with outcome and decision were 75.8 ± 20.7 and 81.1 ± 20.4, respectively. No patients experienced complications. Conclusions: Nonsurgical facial rejuvenation procedures performed by residents can improve patients’ quality of life and provide high satisfaction without compromising safety. Level of Evidence IV: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266. © 2017 Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery


Author Keywords
Facial rejuvenation;  Neurotoxin;  Plastic surgery education;  Residency


Document Type: Article in Press
Source: Scopus

 

https://www.scopus.com/static/images/s.gif10) 

Beirowski, B.a b , Wong, K.M.a , Babetto, E.a c , Milbrandt, J.d e 
MTORC1 promotes proliferation of immature Schwann cells and myelin growth of differentiated Schwann cells
(2017) Proceedings of the National Academy of Sciences of the United States of America, 114 (21), pp. E4261-E4270. 

DOI: 10.1073/pnas.1620761114


a Hunter James Kelly Research Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, United States
b Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, United States
c Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, United States
d Department of Genetics, 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
The myelination of axons in peripheral nerves requires precisely coordinated proliferation and differentiation of Schwann cells (SCs). We found that the activity of the mechanistic target of rapamycin complex 1 (mTORC1), a key signaling hub for the regulation of cellular growth and proliferation, is progressively extinguished as SCs differentiate during nerve development. To study the effects of different levels of sustained mTORC1 hyperactivity in the SC lineage, we disrupted negative regulators of mTORC1, including TSC2 or TSC1, in developing SCs of mutant mice. Surprisingly, the phenotypes ranged from arrested myelination in nerve development to focal hypermyelination in adulthood, depending on the level and timing of mTORC1 hyperactivity. For example, mice lacking TSC2 in developing SCs displayed hyperproliferation of undifferentiated SCs incompatible with normal myelination. However, these defects and myelination could be rescued by pharmacologicalmTORC1 inhibition. The subsequent reconstitution of SC mTORC1 hyperactivity in adult animals resulted in focal hypermyelination. Together our data suggest a model in which high mTORC1 activity promotes proliferation of immature SCs and antagonizes SC differentiation during nerve development. Down-regulation of mTORC1 activity is required for terminal SC differentiation and subsequent initiation of myelination. In distinction to this developmental role, excessive SC mTORC1 activity stimulates myelin growth, even overgrowth, in adulthood. Thus, our work delineates two distinct functions of mTORC1 in the SC lineage essential for proper nerve development and myelination. Moreover, our studies show that SCs retain their plasticity to myelinate and remodel myelin via mTORC1 throughout life.


Author Keywords
Axon;  Mammalian target of rapamycin;  Myelination;  Neuropathy;  Peripheral nerve


Document Type: Article
Source: Scopus

     

 

11) 

Scullin, M.K.a , Kurinec, C.A.a , Nguyen, K.b 
The effects of implementation intention strategies on prospective memory cue encoding
(2017) Journal of Cognitive Psychology, pp. 1-10. Article in Press. 

DOI: 10.1080/20445911.2017.1329205


a Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA


Abstract
Implementation intentions, which include a structured verbal statement and mental imagery, improve prospective memory performance (i.e. remembering to execute delayed intentions). To investigate whether, and how, implementation intention strategies affect encoding processes we had participants complete a thought probe procedure immediately after forming the intention to remember to press Q when seeing fruit words. In Experiment 1, an implementation intention verbal statement (relative to control statement) significantly increased generation of high typicality exemplars (apple, banana, orange). In Experiment 2, an implementation intention imagery procedure (relative to control imagery) produced similar outcomes. In Experiment 3, combining the statement and imagery components of the implementation intention (relative to control statement and imagery) demonstrated even more potent effects (e.g. three-fold increase in fruit exemplars generated). In Experiment 4, we tested whether the control statement versus control imagery procedure differentially affected encoding, but these control procedures showed no significant differences. An interesting, unanticipated finding was that there was significantly less mind wandering in the implementation intention conditions relative to the control conditions. The current experiments provide novel information on the processes operating during intention encoding, and support the classic view that implementation intentions increase the encoding of specific retrieval cues. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
categorical cue;  cue focality;  encoding specificity;  encoding strategy;  Prospective memory


Document Type: Article in Press
Source: Scopus

 

12) 

Patel, C.G., Stavas, M., Perkins, S., Shinohara, E.T.
Central Nervous System Disease, Education, and Race Impact Radiation Refusal in Pediatric Cancer Patients
(2017) Journal of Pediatric Hematology/Oncology, . Article in Press. 

DOI: 10.1097/MPH.0000000000000843


*Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN †Department of Radiation Oncology, Washington University in St Louis, St Louis, MO


Abstract
To investigate the determinants of radiation therapy refusal in pediatric cancer, we used the Surveillance, Epidemiology, and End Results registry to identify 24,421 patients who met the eligibility criteria, diagnosed between 1974 and 2012. Patients had any stage of cancer, were aged 0 to 19, and received radiation therapy or refused radiation therapy when it was recommended. One hundred twenty-eight patients (0.52%) refused radiation therapy when it was recommended. Thirty-two percent of patients who refused radiation therapy ultimately died from their cancer, at a median of 7 months after diagnosis (95% confidence interval, 3-11 mo), as compared with 29.0% of patients who did not refuse radiation therapy died from their cancer, at a median of 17 months after diagnosis (95% confidence interval, 17-18 mo). On multivariable analysis, central nervous system (CNS) site, education, and race were associated with radiation refusal. The odds ratio for radiation refusal for patients with CNS disease was 1.62 (P=0.009) as compared with patients without CNS disease. For patients living in a county with ≥10% residents having less than ninth grade education, the odds ratio for radiation refusal was 1.71 (P=0.008) as compared with patients living in a county with <10% residents having less than ninth grade education. Asian, Pacific Islander, Alaska Native, and American Indian races had an odds ratio of 2.12 (P=0.002) for radiation refusal as compared with black or white race. Although the radiation refusal rate in the pediatric cancer population is low, we show that CNS site, education level, and race are associated with a significant difference in radiation refusal. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Document Type: Article in Press
Source: Scopus

 

13) 

Elpers, K.a , Amano, T.b , DeCoster, V.a , Johnson, M.c 
Effectiveness of a psycho-educational staff training program on attitudes of staff in a long-term care facility: A pilot study and framework
(2017) Educational Gerontology, pp. 1-9. Article in Press. 

DOI: 10.1080/03601277.2017.1321352


a Social Work Department, University of Southern Indiana, Evansville, Indiana, USA
b Brown School of Social Work, Washington University, St. Louis, Missouri, USA
c Deaconess Cross Pointe Outpatient Programs, Evansville, Indiana, USA


Abstract
Managing Behavioral and Psychological Symptoms of Dementia (BPSD) is a significant challenge for staff working in long-term care facilities. This study examines the effectiveness of a psycho-educational training aimed at changing staff’s attitudes. The results indicated that participants’ attitudes toward dementia were more positive, person-centered, and hopeful; some participants’ attitudes were unchanged or altered negatively after the training sessions. The conclusiveness of evaluation findings was limited due to time constraints for staff to participate in the complete educational program and the small dataset. Further research is indicated to revise the methodology of the training to ascertain if the framework regarding education on dementia influences staff’s attitude and the overall well-being of the residents. © 2017 Taylor & Francis


Document Type: Article in Press
Source: Scopus

 

14) 

Lewis, J.S., Jr.a b , Chernock, R.D.c d , Bishop, J.A.e f 
Squamous and Neuroendocrine Specific Immunohistochemical Markers in Head and Neck Squamous Cell Carcinoma: A Tissue Microarray Study
(2017) Head and Neck Pathology, pp. 1-9. Article in Press. 

DOI: 10.1007/s12105-017-0825-y


a Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States
b Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, United States
c Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, United States
d Department of Otolaryngology Head and Neck Surgery, Washington University in St. Louis, St. Louis, MO, United States
e Department of Pathology, The Johns Hopkins University, Baltimore, MD, United States
f Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University, Baltimore, MD, United States


Abstract
The performance characteristics of neuroendocrine-specific and squamous-specific immunohistochemical markers in head and neck squamous cell carcinomas (SCC), in particular in oropharyngeal tumors in this era of human papillomavirus (HPV)-induced cases, are not well-established. The differential diagnosis for poorly differentiated SCCs, for nonkeratinizing oropharyngeal SCCs, and for other specific SCC variants such as basaloid SCC and undifferentiated (or lymphoepithelial-like) carcinomas includes neuroendocrine carcinomas. Given that neuroendocrine carcinomas of the head and neck are aggressive regardless of HPV status, separating them from SCC is critically important. In this study, we examined the neuroendocrine markers CD56, synaptophysin, and chromogranin-A along with the squamous markers p40 and cytokeratin 5/6 in a large tissue microarray cohort of oral, oropharyngeal, laryngeal, and hypopharyngeal SCCs with known HPV results by RNA in situ hybridization for the oropharyngeal tumors. Results were stratified by site and specific SCC variant. The neuroendocrine stains were rarely expressed in SCC (<1% overall) with CD56 the least, and chromogranin-A the most, specific markers. Further, p40 and cytokeratin 5/6 were very consistently expressed in all head and neck SCC (>98% overall), including very strong, consistent staining in oropharyngeal HPV-related nonkeratinizing SCC. Undifferentiated (or lymphoepithelial-like) carcinomas of the oropharynx are more frequently p40 or cytokeratin 5/6 negative or show only weak or focal expression. In summary, markers of neuroendocrine and squamous differentiation show very high specificity and sensitivity, respectively, across the different types of head and neck SCC. © 2017 Springer Science+Business Media New York


Author Keywords
Head and neck;  Human papillomavirus;  Immunohistochemistry;  Neuroendocrine;  Oropharyngeal;  p40;  Squamous cell carcinoma


Document Type: Article in Press
Source: Scopus

 

15) 

Burmeister, J.a , Rathgeb, S.b , Herzog, J.b c 
Cochlear implantation in patients with otosclerosis of the otic capsule
(2017) American Journal of Otolaryngology - Head and Neck Medicine and Surgery, . Article in Press. 

DOI: 10.1016/j.amjoto.2017.05.011


a Des Peres Hospital Otolaryngology Residency, 2345 Dougherty Ferry Rd., St. Louis, MO 63122, United States
b Center for Hearing and Balance Disorders, 226 South Woods Mill Road, Suite 58 West, Chesterfield, MO 63017, United States
c Department of Otolaryngology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, United States


Abstract
Objective: To evaluate outcomes of cochlear implantation of patients with otosclerosis of the otic capsule. Study design: A retrospective case series of 6 patients (7 ears). Patients: 6 patients (7 ears), 5 patients with severe to profound sensorineural hearing loss; 1 patient with mild to profound sensorineural hearing loss, with radiologic evidence of otosclerosis. All patients were adult males, with or without history of stapes surgery. Intervention: Cochlear implantation of 7 ears. 5 patients with severe to profound sensorineural hearing loss received the Nucleus Contour Advance peri-modiolar electrode array with binaural implantation performed in one patient. One patient with mild to profound sensorineural hearing loss received a Cochlear® Nucleus Hybrid L24 device. Methods: Preoperative temporal bone CT, audiometric and speech perception testing scores were reviewed, confirming presence of otosclerosis of the cochlea as well as cochlear implant candidacy. Speech perception testing included CNC words, HINT sentences and AZ Bio scores to measure hearing outcomes post implantation. Results: All recipients of the contour advance device had a significant improvement in hearing at both 3 and 6month follow up. The hybrid device recipient experienced loss of residual hearing in the implanted ear without improvement at 3months and mild improvement at 6months. Conclusion: Cochlear implantation has proven to be effective in the treatment of patients with sensorineural hearing loss, including those with otosclerosis of the cochlea. Hybrid candidacy in the setting of otosclerosis of the cochlea may require consideration of alternative electrode devices, most likely a peri-modiolar device. © 2017.


Author Keywords
Cochlear implant;  Otic capsule;  Otosclerosis


Document Type: Article in Press
Source: Scopus

 

16) 

Luksanapruksa, P.a , Buchowski, J.M.b , Wright, N.M.c , Valone, F.H., IIIb , Peters, C.b , Bumpass, D.B.d 
Outcomes and effectiveness of posterior occipitocervical fusion for suboccipital spinal metastases
(2017) Journal of Neurosurgery: Spine, 26 (5), pp. 554-559. 

DOI: 10.3171/2016.10.SPINE16392


a Department of Orthopaedic Surgery, Washington University in St. Louis, BJC Institute of Health, St. Louis, MO, United States
b Department of Orthopaedic Surgery, Washington University, 425 S Euclid Ave., St. Louis, MO, United States
c Department of Neurosurgery, Washington University, St. Louis, MO, United States
d Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, AK, United States


Abstract
OBJECTIVE: The incidence of suboccipital spinal metastases is rare but has increased given cancer patients' longer life expectancies. Operative treatment in this region is often challenging because of limited fixation points due to tumor lysis, as well as adjacent neural and vascular anatomy. Few studies have reported on this population of cancer patients. The purpose of this study was to evaluate clinical outcomes and complications of patients with suboccipital spinal metastases who had undergone posterior occipitocervical fixation. METHODS: A single-institution database was reviewed to identify patients with suboccipital metastases who had undergone posterior-only instrumented fusion between 1999 and 2014. Clinical presentation, perioperative complications, and postoperative results were analyzed. Pain was assessed using the visual analog scale. Survival analysis was performed using a Kaplan-Meier curve. The revised Tokuhashi and the Tomita scoring systems were used for prognosis prediction. RESULTS: Fifteen patients were identified, 10 men and 5 women with mean age of 64.8 ± 11.8 years (range 48-80 years). Severe neck pain without neurological deficit was the most common presentation. Primary tumors included lung, breast, bladder, myeloma, melanoma, and renal cell cancers. All tumors occurred in the axis vertebra. Preoperative Tokuhashi and Tomita scores ranged from 5 to 13 and 3 to 7, respectively. All patients had undergone occipitocervical fusion of a mean of 4.6 levels (range 2-7 levels). Median survival was 10.3 months. In all cases, neck pain markedly improved and patients were able to resume activities of daily living. The average postoperative pain score was significantly improved as compared with the average preoperative score (1.90 ± 2.56 and 5.50 ± 2.99, respectively, p = 0.01). Three patients experienced postoperative medical complications including urinary tract infection, deep vein thrombosis, myocardial infarction, and cardiac arrhythmia. In the follow-up period, no wound infections or reoperations occurred and no patients experienced spinal cord deficits from tumor recurrence. CONCLUSIONS: Posterior-only occipitocervical stabilization was highly effective at relieving patients' neck pain. No instrumentation failures were noted, and no neurological complications or tumor progression causing spinal cord deficits was noted in the follow-up period. © AANS, 2017.


Author Keywords
Cervical spine;  Occipitocervical fusion;  Oncology;  Posterior surgery;  Suboccipital spinal metastases


Document Type: Article
Source: Scopus

 

17) 

Spudich, S.S.a , Ances, B.M.b 
CROI 2017: Neurologic complications of HIV infection
(2017) Topics in Antiviral Medicine, 25 (2), pp. 69-76. 


a Yale University School of Medicine in New HavenCT, United States
b Washington University in St LouisMO, United States


Abstract
The brain is a major target for HIV infection and is a potential viral reservoir even in virologically wellcontrolled HIV-infected individuals. Data presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) suggested that during early HIV infection, CD4+ T cells in the meninges and choroid plexus serve as an important early site of HIV infection in the central nervous system (CNS), with brain macrophages and microglial cells becoming an important source of viral replication with advancing disease. Longitudinal evaluations of HIV-associated neurocognitive disorder (HAND) demonstrated that cognitive changes occur during early HIV infection and may remain during chronic infection despite virologic control by antiretroviral therapy. Cerebrospinal fluid escape during treatment was noted in numerous cohorts and pathogenetically evaluated as a state of persistent CNS HIV infection despite antiretroviral therapy. Non-HIV risk factors identified for cognitive impairment were depression and frailty. Questions remain concerning appropriate cognitive screening tests to evaluate for HAND. Additional studies highlighted the increasing role of neuroimaging to longitudinally assess potential changes in brain integrity in individuals on systemically suppressive therapy, and provided new CNS considerations in antiretroviral regimens. © 2017, IAS-USA. All rights reserved.


Author Keywords
2017;  Central nervous system;  Cerebrospinal fluid;  Cognition;  CROI;  HAND;  HIV;  Neurocognitive disorder;  Neuroimaging;  Neuropathogenesis;  Reservoir;  Stroke


Document Type: Review
Source: Scopus

 

18) 

Mei, Y.a , Bi, W.L.a b c , Greenwald, N.F.a b c , Agar, N.Y.a b , Beroukhim, R.b c d , Dunn, G.P.e , Dunn, I.F.a d 
Genomic profile of human meningioma cell lines
(2017) PLoS ONE, 12 (5), art. no. e0178322, . 

DOI: 10.1371/journal.pone.0178322


a Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
b Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States
c Broad Institute of mit and Harvard, Cambridge, MA, United States
d Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
e Department of Neurosurgery, Pathology, and Immunology, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Meningiomas, derived from arachnoid cap cells, are the most common intracranial tumor. High-grade meningiomas, as well as those located at the skull base or near venous sinuses, frequently recur and are challenging to manage. Next-generation sequencing is identifying novel pharmacologic targets in meningiomas to complement surgery and radiation. However, due to the lack of in vitro models, the importance and implications of these genetic variants in meningioma pathogenesis and therapy remain unclear. We performed whole exome sequencing to assess single nucleotide variants and somatic copy number variants in four human meningioma cell lines, including two benign lines (HBL-52 and Ben-Men-1) and two malignant lines (IOMM-Lee and CH157-MN). The two malignant cell lines harbored an elevated rate of mutations and copy number alterations compared to the benign lines, consistent with the genetic profiles of high-grade meningiomas. In addition, these cell lines also harbored known meningioma driver mutations in neurofibromin 2 (NF2) and TNF receptorassociated factor 7 (TRAF7). These findings demonstrate the relevance of meningioma cell lines as a model system, especially as tools to investigate the signaling pathways of, and subsequent resistance to, therapeutics currently in clinical trials. © 2017 Mei 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

 

19) 

Zhou, Q.a , Womer, F.Y.b , Kong, L.a , Wu, F.a , Jiang, X.c , Zhou, Y.d , Wang, D.a , Bai, C.c , Chang, M.c , Fan, G.c , Xu, K.c , He, Y.e , Tang, Y.a d , Wang, F.a f 
Trait-related cortical-subcortical dissociation in bipolar disorder: Analysis of network degree centrality
(2017) Journal of Clinical Psychiatry, 78 (5), pp. 584-591. 

DOI: 10.4088/JCP.15m10091


a Department of Psychiatry, First Affiliated Hospital of China Medical University, 155 Nanjing North St, Heping District, Shenyang, Liaoning, China
b Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
c Department of Radiology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
d Department of Gerontology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
e State Key Lab. of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, China
f Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States


Abstract
Background: Bipolar disorder is a systemic brain disorder. Accumulated evidence suggested that cortical-subcortical imbalance could be a trait-related pathogenic factor of bipolar disorder. Degree centrality, a robust index of focal connectivity in which the number of direct connections from one node to all nodes is counted, has not previously been studied in bipolar disorder as a whole. Methods: Resting state functional magnetic resonance imaging was performed on 52 patients with DSM-IV bipolar I disorder and 70 healthy controls recruited between September 2009 and July 2014. Degree centrality was calculated within cerebral gray matter for each subject and compared between patients with bipolar disorder and healthy controls. Hub distributions of both groups were explored. Effects of medication exposure and mood state on degree centrality, as well as cortical-subcortical degree centrality correlations, were explored. Results: Compared to healthy controls, patients with bipolar disorder exhibited significant decrease in degree centrality in cortical regions, including the middle temporal pole, inferior temporal gyrus, and ventral prefrontal cortex, but showed significant increase in degree centrality mainly in subcortical regions, including caudate, thalamus, parahippocampal gyrus, hippocampi, anterior cingulate, insula, and amygdala, and a small portion of cortical regions, such as superior and middle frontal gyrus (P < .05, corrected). Spatial distributions of the 2 groups were very similar. No significant effects of medication exposure or mood state on degree centrality were found. Patients with bipolar disorder also showed significant decrease in cortical-subcortical degree centrality correlation (P = .003). Conclusions: These findings further contribute to the mounting evidence of cortical-subcortical dissociation in bipolar disorder pathophysiology. In addition, this study supports the continued development and implementation of graph-based techniques to enhance our understanding of the underlying neural mechanisms in mental disorders such as bipolar disorder, which are increasingly viewed as systemic brain disorders rather than disorders arising from disruption within a single structure or a limited number of structures. Due to the heterogeneity of our sample, as well as the small sample size of each medication and mood state subgroups, further investigation is needed to support our findings. © 2017 Copyright Physicians Postgraduate Press, Inc.


Document Type: Article
Source: Scopus

 

20) 

Reno, C.M.a b , Puente, E.C.a , Sheng, Z.c , Daphna-Iken, D.a , Bree, A.J.a , Routh, V.H.c , Kahn, B.B.d , Fisher, S.J.a b 
Brain GLUT4 knockout mice have impaired glucose tolerance, decreased insulin sensitivity, and impaired hypoglycemic counterregulation
(2017) Diabetes, 66 (3), pp. 587-597. 

DOI: 10.2337/db16-0917


a Division of Endocrinology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, United States
b Division of Endocrinology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States
c Department of Pharmacology and Physiology, Rutgers New Jersey Medical School, Newark, NJ, United States
d Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Boston, MA, United States


Abstract
GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. © 2017 by the American Diabetes Association.


Document Type: Article
Source: Scopus

 

21) 

Saggar, M.a , Tsalikian, E.b , Mauras, N.c , Mazaika, P.a , White, N.H.d , Weinzimer, S.e , Buckingham, B.f , Hershey, T.d , Reiss, A.L.a 
Compensatory hyperconnectivity in developing brains of young children with type 1 diabetes
(2017) Diabetes, 66 (3), pp. 754-762. Cited 1 time.

DOI: 10.2337/db16-0414


a Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, CA, United States
b Division of Endocrinology and Diabetes, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, United States
c Pediatric Endocrinology, Nemours Children's Health System, Jacksonville, FL, United States
d Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
e Department of Pediatrics, Yale University School of Medicine, New Haven, CT, United States
f Division of Endocrinology and Diabetes, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States


Abstract
Sustained dysregulation of blood glucose (hyper-or hypoglycemia) associated with type 1 diabetes (T1D) has been linked to cognitive deficits and altered brain anatomy and connectivity. However, a significant gap remains with respect to how T1D affects spontaneous at-rest connectivity in young developing brains. Here, using a large multisite study, resting-state functional MRI data were examined in young children with T1D (n = 57;mean age = 7.88 years; 27 females) as compared with age-matched control subjects without diabetes (n = 26; mean age = 7.43 years; 14 females). Using both model-driven seedbased analysis and model-free independent component analysis and controlling for age, data acquisition site, and sex, converging results were obtained, suggesting increased connectivity in young children with T1D as compared with control subjects without diabetes. Further, increased connectivity in children with T1D was observed to be positively associated with cognitive functioning. The observed positive association of connectivity with cognitive functioning in T1D, without overall group differences in cognitive function, suggests a putative compensatory role of hyperintrinsic connectivity in the brain in children with this condition. Altogether, our study attempts to fill a critical gap in knowledge regarding how dysglycemia in T1D might affect the brain's intrinsic connectivity at very young ages. © 2017 by the American Diabetes Association.


Document Type: Article
Source: Scopus

 

22) 

Racette, B.A.a b , Gross, A.a , Criswell, S.R.a , Checkoway, H.c , Searles Nielsen, S.a 
A screening tool to detect clinical manganese neurotoxicity
(2017) NeuroToxicology, . Article in Press. 

DOI: 10.1016/j.neuro.2017.02.009


a Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA
b School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 27 St. Andrews Road, Parktown 2193, South Africa
c University of California, San Diego, Department of Family Medicine and Public Health, Department of Neurosciences, La Jolla, CA, USA


Abstract
Manganese (Mn) over-exposure in occupational settings is associated with basal ganglia toxicity and a movement disorder characterized by parkinsonism (i.e., the signs and symptoms of Parkinson disease). A simple test to help non-neurologists identify workers with clinical Mn neurotoxicity represents an unmet need. In a cohort of Mn-exposed workers from welding worksites, with extensive clinical data, we developed a linear regression model to predict the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score. We primarily considered factors easily obtained in a primary care or occupational medicine clinic, specifically easily assessed signs of parkinsonism and factors likely to be associated with UPDRS3 such as age, timed motor task results, and selected symptoms/conditions. Secondarily we considered other demographic variables and welding exposure. We based the model on 596 examined workers age. ≤. 65. years and with timed motor task data. We selected the model based on simplicity for clinical application, biologic plausibility, and statistical significance and magnitude of regression coefficients. The model contained age, timed motor task scores for each hand, and indicators of action tremor, speech difficulty, anxiety, depression, loneliness, pain and current cigarette smoking. When we examined how well the model identified workers with clinically significant parkinsonism (UPDRS3. ≥. 15) the receiver operating characteristic area under the curve (AUC) was 0.72 (95% confidence interval [CI] 0.67, 0.77). With a cut point that provided 80% sensitivity, specificity was 52%, the positive predictive value in our cohort was 29%, and the negative predictive value was 92%. Using the same cut point for predicted UPDRS3, the AUC was nearly identical for UPDRS3. ≥. 10, and was 0.83 (95% CI 0.76, 0.90) for UPDRS3. ≥. 20. Since welding exposure data was not required after including its putative effects, this model may help identify workers with clinically significant Mn neurotoxicity in a variety of settings, as a first step in a tiered occupational screening program. © 2017 Elsevier B.V.


Author Keywords
Manganese;  Parkinsonism;  Predictive model;  Welding


Document Type: Article in Press
Source: Scopus

 

23) 

Tandon, M., Giedinghagen, A.
Disruptive Behavior Disorders in Children 0 to 6 Years Old
(2017) Child and Adolescent Psychiatric Clinics of North America, . Article in Press. 

DOI: 10.1016/j.chc.2017.02.005


Division of Child and Adolescent Psychiatry, Washington University in St. Louis School of Medicine, 660 South Euclid Avenue, Box 8134, St Louis, MO, USA


Abstract
Disruptive behavior disorders (DBDs), specifically oppositional defiant disorder and conduct disorder, are common, serious, and treatable conditions among preschoolers. DBDs are marked by frequent aggression, deceitfulness, and defiance, and often persist through the lifespan. Exposure to harsh or inconsistent parenting, as frequently seen with parental depression and stress, increases DBD risk. Candidate genes that may increase DBD risk in the presence of childhood adversity have also been identified, but more research is needed. Neurophysiologic and structural correlates with DBD also exist. Parent management training programs, focusing on increasing parenting competence and confidence, are the gold standard treatment of preschool DBDs. © 2017 Elsevier Inc.


Author Keywords
Conduct disorder;  Disruptive behavior;  Oppositional defiant disorder;  Preschool children


Document Type: Article in Press
Source: Scopus

 

24) 

Hirbe, A.C.a b , Cosper, P.F.b c , Dahiya, S.d , Van Tine, B.A.a b 
Neoadjuvant Ifosfamide and Epirubicin in the Treatment of Malignant Peripheral Nerve Sheath Tumors
(2017) Sarcoma, 2017, art. no. 3761292, . 

DOI: 10.1155/2017/3761292

a Division of Medical Oncology, Department of Medicine, Washington University, School of Medicine, 660 South Euclid Ave., St. Louis, MO, United States
b Siteman Cancer Center, St. Louis, MO, United States
c Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Ave., St. Louis, MO, United States


Abstract
Background and Objectives. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with poor overall survival. Response to chemotherapy has been debated for these tumors. Methods. We performed a retrospective analysis of the patients at our institution with a biopsy-proven diagnosis of MPNST that underwent neoadjuvant chemotherapy prior to surgery. Results. We retrospectively identified five patients who received neoadjuvant chemotherapy with epirubicin and ifosfamide that demonstrated a 30% reduction in tumor growth and a 60% response rate by RECIST criteria. Additionally, a metabolic response was observed in all three patients who received serial PET scans during neoadjuvant treatment. The clinical benefit rate, which includes stable disease, was 100%. Conclusions. Our data suggest that MPNSTs do respond to epirubicin and ifosfamide based chemotherapy and prospective studies are warranted to further define the clinical benefit. © 2017 Angela C. Hirbe et al.


Document Type: Article
Source: Scopus

 

 

June 5, 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) 

Waters, E.A., Ball, L., Gehlert, S.
“I don't believe it.” Acceptance and skepticism of genetic health information among African-American and White smokers
(2017) Social Science and Medicine, 184, pp. 153-160. 

DOI: 10.1016/j.socscimed.2017.04.053

Washington University in St. Louis, United States


Abstract
Rationale Effective translation of genomics research into practice depends on public acceptance of genomics-related health information. Objective To explore how smokers come to accept or reject information about the relationship between genetics and nicotine addiction. Methods Thirteen focus groups (N = 84) were stratified by education (seven < Bachelor's degree, six ≥ Bachelor's degree) and race (eight black, five white). Participants viewed a 1-min video describing the discovery of a genetic variant associated with increased risk of nicotine addiction and lung cancer. Next, they provided their opinions about the information. Two coders analyzed the data using grounded theory. Results Pre-video knowledge about why people smoke cigarettes and what genetic risk means informed beliefs about the relationship between genes and addiction. These beliefs were not always consistent with biomedical explanations, but formed the context through which participants processed the video's information. This, in turn, led to information acceptance or skepticism. Participants explained their reactions in terms of the scientific merits of the research and used their existing knowledge and beliefs to explain their acceptance of or skepticism about the information. Conclusion Laypeople hold complex understandings of genetics and addiction. However, when lay and biomedical explanations diverge, genetics-related health information may be rejected. © 2017 Elsevier Ltd


Author Keywords
Gene-environment interaction;  Health communication;  Information processing;  Message rejection;  Tobacco use


Document Type: Article
Source: Scopus



3) 

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


4) 

Haspel, J.
An "eye" for rhythm
(2017) Science Translational Medicine, 9 (390), art. no. 4288, . 

DOI: 10.1126/scitranslmed.aan4288

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


Abstract
A new analytical method allows reconstruction of circadian gene expression in human biopsy samples.


Document Type: Review
Source: Scopus



5) 

Eggebrecht, A.T.a , Culver, J.P.a b c 
Imaging brain function in children with autism spectrum disorder with diffuse optical tomography
(2016) Optics InfoBase Conference Papers, 3 p. 

DOI: 10.1364/TRANSLATIONAL.2016.JW3A.25

a Department of Radiology, St. Louis, MO, United States
b Department of Physics, St. Louis, MO, United States
c Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States


Abstract
We present a feasibility study on applying diffuse optical tomography to school-aged children with autism. Feasibility is tested via assessments of raw data quality and functional activations to language processing and social-perception paradigms. © OSA 2016.


Document Type: Conference Paper
Source: Scopus



6) 

Orukari, I.a , Bauer, A.Q.b , Baxter, G.A.b , Rubin, J.B.c , Culver, J.P.a b 
Alterations in resting state networks in a mouse model of glioma growth
(2016) Optics InfoBase Conference Papers, 3 p. 

DOI: 10.1364/TRANSLATIONAL.2016.JM3A.45

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


Abstract
The relationship between brain tumor growth and alterations in resting state networks is poorly understood. Functional connectivity optical intrinsic imaging enables assessment of resting state alterations in a mouse model of glioma growth. © OSA 2016.


Document Type: Conference Paper
Source: Scopus