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

Neuroscience Publications Archive - March 2017

Weekly Scopus Report

March 25, 2017

March 17, 2017

March 5, 2017

 

March 25, 2017

1) 

Taylor, G.T.a b , Manzella, F.M.a c , Huffman, J.a , Cabrera, O.H.a c , Hoffman, J.d 
Cognition in female rats after blocking conversion of androgens to estrogens
(2017) Hormones and Behavior, 90, pp. 84-89. 

DOI: 10.1016/j.yhbeh.2017.02.011


a Behavioral Neuroscience Program, Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, United States
b Interfakultäre Biomedizinische Forschungseinrichtung (IBF) der Universität Heidelberg, Heidelberg, Germany
c Department of Psychiatry, Washington University in St. Louis School of Medicine, 660 S. Euclid, St. Louis, MO, United States
d Department of Psychology, University of South Florida, Tampa, FL, United States


Abstract
Women and non-human females have surprisingly high levels of circulating testosterone, yet the effects of androgens on non-reproductive behaviors, including cognition, of females are not well characterized. The current project used an aromatase inhibitor, letrozole, to block conversion of androgens to estrogens. Adult female rats were ovariectomized and administered either vehicle only, testosterone propionate only (400 μg/kg, TP only), letrozole only (1 mg/kg, Letro only), or the combination of letrozole and testosterone (TP + Letro) over 4 weeks. A gonadally intact group was used for comparisons. During the last 3 weeks, the animals were tested for working memory in both a spatial task (radial arm maze) and a non-spatial task (object recognition). At sacrifice, uterine weights and serum testosterone and estradiol were determined. Behavioral results were the intact animals showed better working memories on the object recognition task, but that there were no differences among the ovariectomized groups. In the radial arm maze task, groups with best to worst performance were TP only > Intact = TP + Letro > vehicle = Letro only. Highest to lowest serum titers, for testosterone, were TP + Letro > TP only > Intact = Letro only > vehicle and, for estradiol, Intact > TP only > Vehicle > Letro only = TP + Letro. Our interpretation is that testosterone enhanced spatial performance when bioavailability of both TP and E2 are high, and high testosterone can rescue spatial memory when E2 bioavailability is low. © 2017 Elsevier Inc.


Author Keywords
Aromatase;  Letrozole;  Metabolism;  RAM;  Steroid;  Working memory


Document Type: Article
Source: Scopus

 

2) 

Agenor, A., Dvoracek, L., Leu, A., Hunter, D.A., Newton, P., Yan, Y., Johnson, P.J., Mackinnon, S.E., Moore, A.M., Wood, M.D.
Hyaluronic acid/carboxymethyl cellulose directly applied to transected nerve decreases axonal outgrowth
(2017) Journal of Biomedical Materials Research - Part B Applied Biomaterials, 105 (3), pp. 568-574. 

DOI: 10.1002/jbm.b.33576


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


Abstract
Neuroma management is an unresolved problem. Biomaterials to limit unwanted axonal growth could be a tool to manage neuroma. Hyaluronic acid/carboxymethyl cellulose (HA/CMC) is an antiadhesive, biodegradable material that is nontoxic to nerve. The purpose of this study was to evaluate the efficacy of this biomaterial to limit axonal growth. Rats received a sciatic nerve transection and repair with a short conduit (5 mm) containing HA/CMC, fibrin, or nothing (empty conduit). In another study, nerve was transected and either left undisturbed or wrapped with HA/CMC around the proximal and distal ends. In a final study, nerve was transected and repaired with an HA/CMC wrap. Four weeks following the procedures, nerves were harvested and assessed using histomorphometry to measure axonal regeneration. Axonal regeneration following transection was significantly inhibited by direct axonal contact with HA/CMC, whether within a conduit or wrapped around the transected proximal nerve end. Axonal regeneration following epineurial repair was not affected by HA/CMC wrapped around nerve, demonstrating axonal growth inhibition due to direct contact of regenerating axons with HA/CMC. These studies demonstrate the efficacy of HA/CMC to limit axonal outgrowth by contact with regenerating axons. HA/CMC barriers may prove to be a tool to prevent neuroma formation by inhibiting axonal growth. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 568–574, 2017. © 2015 Wiley Periodicals, Inc.


Author Keywords
axon growth;  hyaluronate;  hyaluronic acid;  neuroma;  peripheral nerve


Document Type: Article
Source: Scopus

 

3) 

Yu, Y.-Q.a b c , Barry, D.M.a b , Hao, Y.a b f , Liu, X.-T.a b g , Chen, Z.-F.a b d e 
Molecular and neural basis of contagious itch behavior in mice
(2017) Science, 355 (6329), pp. 1072-1076. 

DOI: 10.1126/science.aak9748


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


Abstract
Socially contagious itch is ubiquitous in human society, but whether it exists in rodents is unclear. Using a behavioral paradigm that does not entail prior training or reward, we found that mice scratched after observing a conspecific scratching. Molecular mapping showed increased neuronal activity in the suprachiasmatic nucleus (SCN) of the hypothalamus of mice that displayed contagious scratching. Ablation of gastrin-releasing peptide receptor (GRPR) or GRPR neurons in the SCN abolished contagious scratching behavior, which was recapitulated by chemogenetic inhibition of SCN GRP neurons. Activation of SCN GRP/GRPR neurons evoked scratching behavior. These data demonstrate that GRP-GRPR signaling is necessary and sufficient for transmitting contagious itch information in the SCN. The findings may have implications for our understanding of neural circuits that control socially contagious behaviors. © 2017, American Association for the Advancement of Science. All rights reserved.


Document Type: Article
Source: Scopus

 

4) 

Treiman, R.
Learning to Spell Words: Findings, Theories, and Issues
(2017) Scientific Studies of Reading, pp. 1-12. Article in Press. 

DOI: 10.1080/10888438.2017.1296449


Washington University in St. Louis


Abstract
There has been less research on how children learn to spell than on how they learn to read, but a good deal is now known about spelling development. This article reviews studies of normative development, beginning with children’s early scribbles and proceeding to prephonological spelling involving letters, phonologically influenced invented spelling, and more advanced spelling. Most of the studies deal with spelling development in alphabetic writing systems. Theories about how children learn to spell, including constructivist theories, stage and phase theories, dual-route theories, and Integration of Multiple Patterns, are presented and reviewed in light of the research evidence. The final section of the article discusses directions for future research and implications for children with spelling difficulties. © 2017 Society for the Scientific Study of Reading


Document Type: Article in Press
Source: Scopus

 

5) 

Bugg, J.M., Ball, B.H.
The strategic control of prospective memory monitoring in response to complex and probabilistic contextual cues
(2017) Memory and Cognition, pp. 1-21. Article in Press. 

DOI: 10.3758/s13421-017-0696-1


Washington University in St. Louis, CB 1125. 1 Brookings Drive, St. Louis, MO, United States


Abstract
Participants use simple contextual cues to reduce deployment of costly monitoring processes in contexts in which prospective memory (PM) targets are not expected. This study investigated whether this strategic monitoring pattern is observed in response to complex and probabilistic contextual cues. Participants performed a lexical decision task in which words or nonwords were presented in upper or lower locations on screen. The specific condition was informed that PM targets (“tor” syllable) would occur only in words in the upper location, whereas the nonspecific condition was informed that targets could occur in any location or word type. Context was blocked such that word type and location changed every 8 trials. In Experiment 1, the specific condition used the complex contextual cue to reduce monitoring in unexpected contexts relative to the nonspecific condition. This pattern largely was not evidenced when the complex contextual cue was probabilistic (Experiment 2). Experiment 3 confirmed that strategic monitoring is observed for a complex cue that is deterministic, but not one that is probabilistic. Additionally, Experiments 1 and 3 demonstrated a disadvantage associated with strategic monitoring—namely, that the specific condition was less likely to respond to a PM target in an unexpected context. Experiment 3 provided evidence that this disadvantage is attributable to impaired noticing of the target. The novel findings suggest use of a complex contextual cue per se is not a boundary condition for the strategic, context-specific allocation of monitoring processes to support prospective remembering; however, strategic monitoring is constrained by the predictive utility of the complex contextual cue. © 2017 Psychonomic Society, Inc.


Author Keywords
Attention;  Context specific;  Probabilistic;  Prospective memory;  Strategic monitoring


Document Type: Article in Press
Source: Scopus

 

6) 

Huettner, J.E.
TARPs and AMPA Receptors: Function Follows Form
(2017) Neuron, 93 (5), pp. 989-991. 

DOI: 10.1016/j.neuron.2017.02.040


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


Abstract
In this issue of Neuron, Ben-Yaacov et al. (2017) dissect the interaction between AMPA receptors and auxiliary (TARP) subunits, revealing essential roles for the receptor transmembrane and cytoplasmic domains, as well as for the TARP extracellular EX2 loop. © 2017 Elsevier Inc.


Document Type: Short Survey
Source: Scopus

 

7) 

Chen, H.-Y.a , Gilmore, A.W.a , Nelson, S.M.b c d , McDermott, K.B.a e 
Are there multiple kinds of episodic memory? An fMRI investigation comparing autobiographical and recognition memory tasks
(2017) Journal of Neuroscience, 37 (10), pp. 2764-2775. 

DOI: 10.1523/JNEUROSCI.1534-16.2017


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


Abstract
What brain regions underlie retrieval from episodic memory? The bulk of research addressing this question with fMRI has relied upon recognition memory for materials encoded within the laboratory. Another, less dominant tradition has used autobiographical methods, whereby people recall events from their lifetime, often after being cued with words or pictures. The current study addresses how the neural substrates of successful memory retrieval differed as a function of the targeted memory when the experimental parameters were held constant in the two conditions (except for instructions). Human participants studied a set of scenes and then took two types of memory test while undergoing fMRI scanning. In one condition (the picture memory test), participants reported for each scene (32 studied, 64 nonstudied) whether it was recollected from the prior study episode. In a second condition (the life memory test), participants reported for each scene (32 studied, 64 nonstudied) whether it reminded them of a specific event from their preexperimental lifetime. An examination of successful retrieval (yes responses) for recently studied scenes for the two test types revealed pronounced differences; that is, autobiographical retrieval instantiated with the life memory test preferentially activated the default mode network, whereas hits in the picture memory test preferentially engaged the parietal memory network as well as portions of the frontoparietal control network. When experimental cueing parameters are held constant, the neural underpinnings of successful memory retrieval differ when remembering life events and recently learned events. © 2017 the authors.


Author Keywords
Autobiographical memory;  Default mode network;  Episodic memory;  FMRI;  Parietal memory network;  Recognition memory


Document Type: Article
Source: Scopus

 

8) 

Spahn, V.a , Del Vecchio, G.a , Labuz, D.a , Rodriguez-Gaztelumendi, A.a , Massaly, N.a c , Temp, J.a , Durmaz, V.b , Sabri, P.b , Reidelbach, M.b , Machelska, H.a , Weber, M.b , Stein, C.a 
A nontoxic pain killer designed by modeling of pathological receptor conformations
(2017) Science, 355 (6328), pp. 966-969. 

DOI: 10.1126/science.aai8636


a Department of Anesthesiology and Critical Care Medicine, Charité-Universitätsmedizin Berlin Campus Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, Berlin, Germany
b Computational Molecular Design, Zuse-Institut Berlin, Takustrasse 7, Berlin, Germany
c Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide-binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3′,5′-monophosphate inhibition in vitro. It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential. © 2017, American Association for the Advancement of Science. All rights reserved.


Document Type: Article
Source: Scopus

 

9) 

Sergin, I., Jong, Y.-J.I., Harmon, S.K., Kumar, V., O'Malley, K.L.
Sequences within the C terminus of the metabotropic glutamate receptor 5 (mGluR5) are responsible for inner nuclear membrane localization
(2017) Journal of Biological Chemistry, 292 (9), pp. 3637-3655. 

DOI: 10.1074/jbc.M116.757724


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


Abstract
Traditionally, G-protein-coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However, recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5 (mGluR5) is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11. Here, we identified a region within the C-terminal domain (amino acids 852-876) that is necessary and sufficient forINMlocalization of the receptor. Because these sequences do not correspond to known nuclear localization signal motifs, they represent a new motif for INM trafficking. mGluR5 is also trafficked to the plasma membrane where it undergoes re-cycling/degradation in a separate receptor pool, one that does not interact with the nuclear mGluR5 pool. Finally, our data suggest that once at the INM,mGluR5is stably retained via interactions with chromatin. Thus, mGluR5 is perfectly positioned to regulate nucleoplasmic Ca2+ in situ. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.


Document Type: Article
Source: Scopus

 

10) 

Adam Noah, J.a , Dravida, S.a b , Zhang, X.a , Yahil, S.c , Hirsch, J.a d e f g 
Neural correlates of conflict between gestures and words: A domain-specific role for a temporal-parietal complex
(2017) PLoS ONE, 12 (3), art. no. e0173525, . 

DOI: 10.1371/journal.pone.0173525


a Brain Function Laboratory, Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
b Medical Scientist Training Program, Yale School of Medicine, New Haven, CT, United States
c Department of Neurosciences, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
e Department of Neuroscience, Yale School of Medicine, New Haven, CT, United States
f Department of Comparative Medicine, Yale School of Medicine, New Haven, CT, United States
g Department of Medical Physics and Bioengineering, University College London, London, United Kingdom


Abstract
The interpretation of social cues is a fundamental function of human social behavior, and resolution of inconsistencies between spoken and gestural cues plays an important role in successful interactions. To gain insight into these underlying neural processes, we compared neural responses in a traditional color/word conflict task and to a gesture/word conflict task to test hypotheses of domain-general and domain-specific conflict resolution. In the gesture task, recorded spoken words ("yes" and "no") were presented simultaneously with video recordings of actors performing one of the following affirmative or negative gestures: thumbs up, thumbs down, head nodding (up and down), or head shaking (side-to-side), thereby generating congruent and incongruent communication stimuli between gesture and words. Participants identified the communicative intent of the gestures as either positive or negative. In the color task, participants were presented the words "red" and "green" in either red or green font and were asked to identify the color of the letters. We observed a classic "Stroop" behavioral interference effect, with participants showing increased response time for incongruent trials relative to congruent ones for both the gesture and color tasks. Hemodynamic signals acquired using functional near-infrared spectroscopy (fNIRS) were increased in the right dorsolateral prefrontal cortex (DLPFC) for incongruent trials relative to congruent trials for both tasks consistent with a common, domain-general mechanism for detecting conflict. However, activity in the left DLPFC and frontal eye fields and the right temporal-parietal junction (TPJ), superior temporal gyrus (STG), supramarginal gyrus (SMG), and primary and auditory association cortices was greater for the gesture task than the color task. Thus, in addition to domain-general conflict processing mechanisms, as suggested by common engagement of right DLPFC, socially specialized neural modules localized to the left DLPFC and right TPJ including adjacent homologous receptive language areas were engaged when processing conflicting communications. These findings contribute to an emerging view of specialization within the TPJ and adjacent areas for interpretation of social cues and indicate a role for the region in processing social conflict. © 2017 Noah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Document Type: Article
Source: Scopus

 

11) 

Ramratnam, S.K.a , Visness, C.M.b , Jaffee, K.F.b , Bloomberg, G.R.c , Kattan, M.d , Sandel, M.T.e , Wood, R.A.f , Gern, J.E.a , Wright, R.J.g 
Relationships among maternal stress and depression, type 2 responses, and recurrent wheezing at age 3 years in low-income urban families
(2017) American Journal of Respiratory and Critical Care Medicine, 195 (5), pp. 674-681. 

DOI: 10.1164/rccm.201602-0272OC


a University of Wisconsin, School of Medicine and Public Health, Madison, WI, United States
b Rho Inc., Chapel Hill, NC, United States
c Washington University School of Medicine, St. Louis, MO, United States
d Columbia University, College of Physicians and Surgeons, New York, NY, United States
e Boston University, School of Medicine, Boston, MA, United States
f Johns Hopkins University School of Medicine, Baltimore, MD, United States
g Kravis Children's Hospital, Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States


Abstract
Rationale: Maternal depression and prenatal and early life stress may influence childhood wheezing illnesses, potentially through effects on immune development. Objectives: To test the hypothesis that maternal stress and/or depression during pregnancy and early life are associated with recurrent wheezing and aeroallergen sensitivity and altered cytokine responses (enhanced type 2 or reduced virus-induced cytokine responses) from stimulated peripheral blood mononuclear cells at age 3 years. Methods: URECA (Urban Environment and Childhood Asthma) is a birth cohort at high risk for asthma (n = 560) in four inner cities. Maternal stress, depression, and childhood wheezing episodes were assessed by quarterly questionnaires beginning at birth. Logistic and linear regression techniques were used to examine the relation of maternal stress/depression to recurrent wheezing and peripheral blood mononuclear cell cytokine responses at age 3 years. Measurements and Main Results: Overall, 166 (36%) children had recurrent wheeze at age 3 years. Measures of maternal perceived stress at Years 2 and 3 were positively associated with recurrent wheeze (P, 0.05). Maternal depression (any year) was significantly associated with recurrent wheezing (P <0.01). These associations were also significant when considered in a longitudinal analysis of cumulative stress and depression (P <0.02). Neither stress nor depression was significantly related to aeroallergen sensitization or antiviral responses. Contrary to our original hypothesis, prenatal and Year 1 stress and depression had significant inverse associations with several type 2 cytokine responses. Conclusions: In urban children at high risk for asthma, maternal perceived stress and depression were significantly associated with recurrent wheezing but not increased atopy or reduced antiviral responses. Copyright © 2017 by the American Thoracic Society.


Author Keywords
Atopy;  Depression;  Inner city;  Stress;  Wheezing


Document Type: Article
Source: Scopus

 

12) 

Lucey, B.P.a b , Mawuenyega, K.G.a , Patterson, B.W.c , Elbert, D.L.d , Ovod, V.a , Kasten, T.a , Morris, J.C.a b e , Bateman, R.J.a b e 
Associations between β-amyloid kinetics and the β-amyloid diurnal pattern in the central nervous system
(2017) JAMA Neurology, 74 (2), pp. 207-215. 

DOI: 10.1001/jamaneurol.2016.4202


a Department of Neurology, Washington University, School of Medicine, 660 S Euclid Ave, St Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University, School of Medicine, St Louis, MO, United States
c Department of Medicine, Washington University, School of Medicine, St Louis, MO, United States
d Department of Biomedical Engineering, Washington University, St Louis, MO, United States
e Knight Alzheimer's Disease Research Center, Washington University, School of Medicine, St Louis, MO, United States


Abstract
IMPORTANCE Recent studies found that the concentration of amyloid-β (Aβ) fluctuates with the sleep-wake cycle. Although the amplitude of this day/night pattern attenuates with age and amyloid deposition, to our knowledge, the association of Aβ kinetics (ie, production, turnover, and clearance) with this oscillation has not been studied. OBJECTIVE To determine the association between Aβ kinetics, age, amyloid levels, and the Aβ day/night pattern in humans. DESIGN, SETTING, AND PARTICIPANTS We measured Aβ concentrations and kinetics in 77 adults aged 60 to 87 years with and without amyloid deposition by a novel precise mass spectrometrymethod at theWashington University School of Medicine in St Louis, Missouri. We compared findings of 2 orthogonal methods, enzyme-linked immunosorbent assay and mass spectrometry, to validate the day/night patterns and determine more precise estimates of the cosinor parameters. In vivo labeling of central nervous system proteins with stable isotopically labeled leucine was performed, and kinetics of Aβ40 and Aβ42 were measured. INTERVENTIONS Serial cerebrospinal fluid collection via indwelling lumbar catheter over 36 to 48 hours before, during, and after in vivo labeling, with a 9-hour primed constant infusion of 13C6-leucine. MAIN OUTCOMES AND MEASURES The amplitude, linear increase, and other cosinor measures of each participant's serial cerebrospinal fluid Aβ concentrations and Aβ turnover rates. RESULTS Of the 77 participants studied, 46 (59.7%) were men, and the mean (range) age was 72.6 (60.4-87.7) years. Day/night patterns in Aβ concentrations were more sharply defined by the precise mass spectrometrymethod than by enzyme-linked immunosorbent assay (mean difference of SD of residuals: Aβ40, -7.42 pM; P < .001; Aβ42, -3.72 pM; P < .001). Amyloid deposition diminished day/night amplitude and linear increase of Aβ42 but not of Aβ40. Increased age diminished day/night amplitude of both Aβ40 and Aβ42. After controlling for amyloid deposition, amplitude of Aβ40 was positively associated with production rates (r = 0.42; P < .001), while the linear rise was associated with turnover rates (r = 0.28; P < .05). The amplitude and linear rise of Aβ42 were both associated with turnover (r = -0.38; P < .001) and production (r = 0.238; P < .05) rates. CONCLUSIONS AND RELEVANCE Amyloid deposition is associated with premature loss of normal Aβ42 day/night patterns in older adults, suggesting the previously reported effects of age and amyloid on Aβ42 amplitude at least partially affect each other. Production and turnover rates suggest that day/night Aβ patterns are modulated by both production and clearance mechanisms active in sleep-wake cycles and that amyloid deposition may impair normal circadian patterns. These findings may be important for the designs of future secondary prevention trials for Alzheimer disease. © 2017 American Medical Association.


Document Type: Article
Source: Scopus

 

13) 

Ferguson, I.a , Huecker, J.a , Huang, J.b , Mcclelland, C.c , Van Stavern, G.a 
Risk factors for radiation-induced optic neuropathy: A case-control study
(2017) Clinical and Experimental Ophthalmology, . Article in Press. 

DOI: 10.1111/ceo.12927


a Department of Ophthalmology and Visual Sciences Washington University in St. Louis Saint Louis, Missouri USA
b Department of Radiation Oncology Washington University in St. Louis St. Louis, Missouri USA
c Department of Ophthalmology and Visual Neurosciences University of Minnesota Minneapolis, Minnesota USA


Abstract
Importance: Identifying risk factors for radiation-induced optic neuropathy (RION) could promote a more conservative approach to radiation treatment planning in vulnerable patients. Background: This study explored possible factors beyond radiation dose associated with the development of RION after external beam radiation therapy. Design: This was a retrospective case-control study conducted at a university hospital tertiary care center. Participants: Cases (n = 14) meeting criteria for a diagnosis of RION by neuro-ophthalmologic exam were identified from a single-centre neuro-ophthalmology database. Controls (n = 31) without RION were selected from a single-centre radiation oncology database. Methods: Controls were matched to cases based upon maximum radiation dose to the optic apparatus. Patient characteristics and treatment parameters were interrogated by univariate analysis for attributes predisposing to RION. Main Outcome Measures: The primary parameter was a significant association of patient characteristics or treatment parameters with RION. Results: Controlling for radiation dosage, no significant associations for alternative risk factors were identified. Conclusions and Relevance: These results support the literature suggesting that the primary risk factor for developing RION is radiation dosage and that additional patient-related and tumour-related risk factors may play only a minor role. © 2017 Royal Australian and New Zealand College of Ophthalmologists.


Author Keywords
Optic nerve diseases;  Optic neuropathy;  Radiation injury


Document Type: Article in Press
Source: Scopus

 

14) 

Ray, W.Z.
Autologous Schwann cells
(2017) Neurosurgical Focus, 42 (3), art. no. E3, . 

DOI: 10.3171/2016.12.FOCUS16537


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


Document Type: Editorial
Source: Scopus

 

15) 

Saied, N.N.a , Helwani, M.A.b , Weavind, L.M.a , Shi, Y.a c , Shotwell, M.S.a c , Pandharipande, P.P.a 
Effect of anaesthesia type on postoperative mortality and morbidities: A matched analysis of the NSQIP database
(2017) British Journal of Anaesthesia, 118 (1), pp. 105-111. 

DOI: 10.1093/bja/aew383


a Department of Anesthesiology, Vanderbilt University Medical Centre, MAB 403, 1211 21st Ave S, Nashville, TN, United States
b Department of Anesthesiology, Washington University Medical Centre, Campus Box 8054, 660 Euclid Ave, St. Louis, MO, United States
c Department of Biostatistics, Vanderbilt University Medical Centre, MAB 403, 1211 21st Ave S, Nashville, TN, United States


Abstract
Background. The anaesthetic technique may influence clinical outcomes, but inherent confounding and small effect sizes makes this challenging to study. We hypothesized that regional anaesthesia (RA) is associated with higher survival and fewer postoperative organ dysfunctions when compared with general anaesthesia (GA). Methods. We matched surgical procedures and type of anaesthesia using the US National Surgical Quality Improvement database, in which 264,421 received GA and 64,119 received RA. Procedures were matched according to Current Procedural Terminology (CPT) and ASA physical status classification. Our primary outcome was 30-day postoperative mortality and secondary outcomes were hospital length of stay, and postoperative organ system dysfunction. After matching, multiple regression analysis was used to examine associations between anaesthetic type and outcomes, adjusting for covariates. Results. After matching and adjusting for covariates, type of anaesthesia did not significantly impact 30-day mortality. RA was significantly associated with increased likelihood of early discharge (HR 1.09; P< 0.001), 47% lower odds of intraoperative complications, and 24% lower odds of respiratory complications. RA was also associated with 16% lower odds of developing deep vein thrombosis and 15% lower odds of developing any one postoperative complication (OR 0.85; P < 0.001). There was no evidence of an effect of anaesthesia technique on postoperative MI, stroke, renal complications, pulmonary embolism or peripheral nerve injury. Conclusions. After adjusting for clinical and patient characteristic confounders, RA was associated with significantly lower odds of several postoperative complications, decreased hospital length of stay, but not mortality when compared with GA. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.


Author Keywords
General anaesthesia;  Patient outcome;  Regional anaesthesia;  Registry


Document Type: Article
Source: Scopus

 

16) 

Mahan, M.A.a , Ray, W.Z.b , Yang, L.J.S.c , Spinner, R.J.d 
Peripheral nerve surgery
(2017) Neurosurgical Focus, 42 (3), art. no. E1, . 

DOI: 10.3171/2017.1.FOCUS178


a Department of Neurosurgery, University of Utah, Salt Lake City, UT, United States
b Department of Neurosurgery, Washington University, St. Louis, MO, United States
c Department of Neurosurgery, University of Michigan, Ann Arbor, MI, United States
d Department of Neurosurgery, Mayo Clinic, Rochester, MN, United States


Document Type: Editorial
Source: Scopus

 

17) 

Santiago-Tirado, F.H.a , Onken, M.D.b , Cooper, J.A.b , Klein, R.S.c , Doering, T.L.a 
Trojan horse transit contributes to blood-brain barrier crossing of a eukaryotic pathogen
(2017) mBio, 8 (1), art. no. e02183-16, . 

DOI: 10.1128/mBio.02183-16


a Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, United States
c Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting the passage of molecules and microorganisms. Despite this barrier, however, the fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in the lung, and experimental evidence suggests that host phagocytes play a role in subsequent dissemination, although this role remains ill defined. Additionally, the disparate experimental approaches that have been used to probe various potential routes of BBB transit make it impossible to assess their relative contributions, confounding any integrated understanding of cryptococcal brain entry. Here we used an in vitro model BBB to show that a “Trojan horse” mechanism contributes significantly to fungal barrier crossing and that host factors regulate this process independently of free fungal transit. We also, for the first time, directly imaged C. neoformans-containing phagocytes crossing the BBB, showing that they do so via transendothelial pores. Finally, we found that Trojan horse crossing enables CNS entry of fungal mutants that cannot otherwise traverse the BBB, and we demonstrate additional intercellular interactions that may contribute to brain entry. Our work elucidates the mechanism of cryptococcal brain invasion and offers approaches to study other neuropathogens. IMPORTANCE The fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that kills hundreds of thousands of people each year. One route that has been proposed for this brain entry is a Trojan horse mechanism, whereby the fungus crosses the blood-brain barrier (BBB) as a passenger inside host phagocytes. Although indirect experimental evidence supports this intriguing mechanism, it has never been directly visualized. Here we directly image Trojan horse transit and show that it is regulated independently of free fungal entry, contributes to cryptococcal BBB crossing, and allows mutant fungi that cannot enter alone to invade the brain. © 2017 Santiago-Tirado et al.


Document Type: Article
Source: Scopus

 

18) 

Sommerville, R.B., Vincenti, M.G., Winborn, K., Casey, A., Stitziel, N.O., Connolly, A.M., Mann, D.L.
Comments on Letter to the Editor entitled: "Role of electrophysiological evaluation for the best device choice to prevent sudden cardiac death in patients with Myotonic Dystrophy Type1 and Emery Dreifuss Muscular Dystrophy"
(2017) Trends in Cardiovascular Medicine, . Article in Press. 

DOI: 10.1016/j.tcm.2017.02.002


Washington University School of Medicine, Cardiovascular Division, 4940 Parkview Place, NWT Rm 13121, St. Louis, MO 63110, USA


Document Type: Article in Press
Source: Scopus

 

19) 

Iannotti, L.a , Jean Louis Dulience, S.a , Wolff, P.b , Cox, K.a , Lesorogol, C.a , Kohl, P.a 
Nutrition factors predict earlier acquisition of motor and language milestones among young children in Haiti
(2016) Acta paediatrica (Oslo, Norway : 1992), 105 (9), pp. e406-e411. 

DOI: 10.1111/apa.13483


a Institute for Public Health, Brown School, St. Louis, MO, USA
b Washington University Medical School, St. Louis, MO, USA


Abstract
AIM: To examine the nutrition-related factors associated with motor and language development among young children living in a poor urban area of Haiti.

METHODS: Children aged 6-11 months (n = 583) were enrolled and followed monthly for one year. World Health Organization motor developmental milestones and vowel and consonant counts were assessed. Longitudinal regression models were applied to assess the association of anthropometric, dietary intake, infectious disease morbidity and socio-economic and demographic factors on developmental outcomes.

RESULTS: At baseline, 9.4% were stunted or length-for-age Z score < -2, and 30.2% were mild-to-moderately stunted or length-for-age Z score < -1. Stunting status was significantly associated with motor and phonetic language acquisition at each time point during infancy. Several nutrition factors significantly predicted earlier achievement of motor and language development outcomes in longitudinal models: child anthropometry; breastfeeding and complementary feeding frequencies; dietary diversity; egg and oil intake; and reduced infectious disease morbidities. Increases in the length-for-age Z score significantly predicted all motor and language outcomes and yielded the best fit models compared to other anthropometric indicators (p < 0.001).

CONCLUSION: Child development interventions may be enhanced by incorporating nutrition strategies such as improved diet quality, breastfeeding promotion and diarrhoeal disease mitigation. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.


Author Keywords
Anthropometry;  Child feeding practices;  Diarrhoea;  Motor and language developmental milestones


Document Type: Article
Source: Scopus

 

20) 

Kapoor, M.a , Chou, Y.-L.b , Edenberg, H.J.c , Foroud, T.c , Martin, N.G.d , Madden, P.A.b , Wang, J.C.a , Bertelsen, S.a , Wetherill, L.c , Brooks, A.e , Chan, G.f , Hesselbrock, V.f , Kuperman, S.g , Medland, S.E.d , Montgomery, G.d , Tischfield, J.e , Whitfield, J.B.d , Bierut, L.J.b , Heath, A.C.b , Bucholz, K.K.b , Goate, A.M.a , Agrawal, A.b 
Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures
(2016) Translational psychiatry, 6, p. e761. 

DOI: 10.1038/tp.2016.27


a Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
b Washington University School of Medicine, St. Louis, MO, USA
c Indiana University School of Medicine, Indianapolis, IN, USA
d Queensland Institute of Medical Research, Brisbane, QLD, Australia
e Rutgers University, New Brunswick, NJ, USA
f University of Connecticut Health Center, Farmington, CT, USA
g University of Iowa Carver College of Medicine, Iowa City, IA, USA


Abstract
Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.


Document Type: Article
Source: Scopus

 

21) 

Deming, Y.a , Xia, J.a , Cai, Y.a , Lord, J.a , Holmans, P.b , Bertelsen, S.a , Holtzman, D.c , Morris, J.C.c , Bales, K.d , Pickering, E.H.d , Kauwe, J.e , Goate, A.f , Cruchaga, C.g , Alzheimer's Disease Neuroimaging Initiativeh 
A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin
(2016) Neurobiology of aging, 37, pp. 208.e1-9. 

DOI: 10.1016/j.neurobiolaging.2015.09.009


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
b Institute of Psychological Medicine and Clinical Neurosciences, MRC Center for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
d Neuroscience Research Unit, Worldwide Research and Development, Pfizer, Inc., Groton, CT, USA
e Department of Biology, Brigham Young University, Provo, UT, USA
f Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
g Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA


Abstract
Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 × 10(-7)) and interleukin 6 (IL6, p = 9.94 × 10(-6), in the entire data set and in the APOE ε4- individuals p = 7.40 × 10(-8)). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.


Author Keywords
Alzheimer's disease;  APOE;  Cerebrospinal fluid;  Clusterin;  Gene ontology;  Immune response


Document Type: Article
Source: Scopus

 

22) 

Cohen-Shikora, E.R., Balota, D.A.
An examination of age-related changes in the control of lexical and sublexical pathways in mapping spelling to sound
(2016) Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition, 23 (2), pp. 218-233. 

DOI: 10.1080/13825585.2015.1075467


a Department of Psychology , Washington University in St. Louis , St. Louis , MO , USA


Abstract
The current study investigated the extent to which young and older adults are able to direct attention to distinct processes in mapping spelling onto sound. Young and older adults completed either a speeded pronunciation task (reading aloud words) or regularization task (pronouncing words based on spelling-to-sound correspondences, e.g., pronouncing PINT such that it rhymes with HINT) in order to bias processing of lexical, whole-word information, or sublexical, spelling-to-sound mapping, respectively. Both younger and older adults produced reduced word-frequency effects and lexicality effects in the regularization task compared to the normal pronunciation task. Importantly, compared to younger adults, older adults produced exaggerated effects of task (i.e., pronunciation vs. regularization) on the observed frequency and lexicality effects. These results highlight both the flexibility of the lexical processing system and changes in the influence of the underlying lexical route due to additional 50 years of reading experience and/or changes in attentional control.


Author Keywords
aging;  attention;  lexicality;  Word frequency;  word recognition;  word regularity


Document Type: Article
Source: Scopus

March 17, 2017

1) 

Shany, E.a b , Inder, T.E.c , Goshen, S.b , Lee, I.d , Neil, J.J.e , Smyser, C.D.d f j , Doyle, L.W.g h i , Anderson, P.J.h i , Shimony, J.S.j 
Diffusion Tensor Tractography of the Cerebellar Peduncles in Prematurely Born 7-Year-Old Children
(2017) Cerebellum, 16 (2), pp. 314-325. 

DOI: 10.1007/s12311-016-0796-7


a Department of Neonatology, Soroka Medical Center, P.O. Box 151, Beer Sheva, Israel
b Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
c Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA, United States
d Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Boston Children’s Hospital, Boston, MA, United States
f Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Melbourne, Australia
h Clinical Sciences, Murdoch Children’s Research Institute, Melbourne, Australia
i Department of Paediatrics, The University of Melbourne, Melbourne, Australia
j Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The objective of this study was to correlate neurodevelopmental outcome of preterm-born children and their perinatal clinical and imaging characteristics with diffusion magnetic resonance imaging (MRI) measures of the three cerebellar peduncles at age 7. Included in this prospective longitudinal study were 140 preterm-born children (<30 weeks gestation) who underwent neurodevelopmental assessment (IQ, motor, language, working memory) and diffusion-weighted imaging (DWI) at age 7 years. White matter tracts in the superior, middle, and inferior cerebellar peduncles were delineated using regions of interest drawn on T2-weighted images and fractional anisotropy (FA) maps. Diffusion measures (mean diffusivity (MD) and FA) and tract volumes were calculated. Linear regression was used to assess relationships with outcome. The severity of white matter injury in the neonatal period was associated with lower FA in the right superior cerebellar peduncle (SCP) and lower tract volumes of both SCPs and middle cerebellar peduncles (MCPs). In the MCP, higher IQ was associated with lower MD in the whole group and higher FA in right-handed children. In the SCP, lower motor scores were associated with higher MD and higher language scores were associated with higher FA. These associations remained significant in multivariable models. This study adds to the body of literature detailing the importance of cerebellar involvement in cognitive function related to reciprocal connections with supratentorial structures. © 2016, Springer Science+Business Media New York.


Author Keywords
Cerebellum;  Magnetic resonance imaging;  Neurodevelopmental outcome;  Premature infants


Document Type: Article
Source: Scopus

 

2) 

Yokoyama, J.S.a , Karch, C.M.b , Fan, C.C.c , Bonham, L.W.a , Kouri, N.d , Ross, O.A.d , Rademakers, R.d , Kim, J.d , Wang, Y.e , Höglinger, G.U.f , Müller, U.g , Ferrari, R.h , Hardy, J.h , International Ftd-Genomics Consortium (Ifgc)p , Momeni, P.i , Sugrue, L.P.j , Hess, C.P.j , James Barkovich, A.j , Boxer, A.L.a , Seeley, W.W.a , Rabinovici, G.D.a , Rosen, H.J.a , Miller, B.L.a , Schmansky, N.J.k , Fischl, B.k l , Hyman, B.T.m , Dickson, D.W.d , Schellenberg, G.D.n , Andreassen, O.A.f , Dale, A.M.c o , Desikan, R.S.j 
Shared genetic risk between corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia
(2017) Acta Neuropathologica, pp. 1-13. Article in Press. 

DOI: 10.1007/s00401-017-1693-y


a Department of Neurology, Memory and Aging Center, University of California, San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, United States
b Department of Psychiatry, Washington University, St. Louis, MO, United States
c Department of Cognitive Sciences, University of California, San Diego, La Jolla, CA, United States
d Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, United States
e NORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
f Department of Neurology, Technical University of Munich, Munich, Germany and German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
g Institut for Humangenetik, Justus-Liebig-Universität, Giessen, Germany
h Department of Molecular Neuroscience, Institute of Neurology, UCL, London, United Kingdom
i Laboratory of Neurogenetics, Department of Internal Medicine, Texas Tech University Health Science Center, Lubbock, TX, United States
j Neuroradiology Section, L-352, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, United States
k Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States
l Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology, Cambridge, MA, United States
m Department of Neurology, Massachusetts General Hospital, Charlestown, MA, United States
n Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
o Departments of Radiology and Neurosciences, University of California, San Diego, La Jolla, CA, United States


Abstract
Corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and a subset of frontotemporal dementia (FTD) are neurodegenerative disorders characterized by tau inclusions in neurons and glia (tauopathies). Although clinical, pathological and genetic evidence suggests overlapping pathobiology between CBD, PSP, and FTD, the relationship between these disorders is still not well understood. Using summary statistics (odds ratios and p values) from large genome-wide association studies (total n = 14,286 cases and controls) and recently established genetic methods, we investigated the genetic overlap between CBD and PSP and CBD and FTD. We found up to 800-fold enrichment of genetic risk in CBD across different levels of significance for PSP or FTD. In addition to NSF (tagging the MAPT H1 haplotype), we observed that SNPs in or near MOBP, CXCR4, EGFR, and GLDC showed significant genetic overlap between CBD and PSP, whereas only SNPs tagging the MAPT haplotype overlapped between CBD and FTD. The risk alleles of the shared SNPs were associated with expression changes in cis-genes. Evaluating transcriptome levels across adult human brains, we found a unique neuroanatomic gene expression signature for each of the five overlapping gene loci (omnibus ANOVA p &lt; 2.0 × 10−16). Functionally, we found that these shared risk genes were associated with protein interaction and gene co-expression networks and showed enrichment for several neurodevelopmental pathways. Our findings suggest: (1) novel genetic overlap between CBD and PSP beyond the MAPT locus; (2) strong ties between CBD and FTD through the MAPT clade, and (3) unique combinations of overlapping genes that may, in part, influence selective regional or neuronal vulnerability observed in specific tauopathies. © 2017 Springer-Verlag Berlin Heidelberg


Document Type: Article in Press
Source: Scopus

 

3) 

Pappa, K., Doty, T., Taff, S.D., Kniepmann, K., Foster, E.R.
Self-Management Program Participation and Social Support in Parkinson's Disease: Mixed Methods Evaluation
(2017) Physical and Occupational Therapy in Geriatrics, pp. 1-18. Article in Press. 

DOI: 10.1080/02703181.2017.1288673


Program in Occupational Therapy, Washington University School of Medicine, St. Louis, Missouri, USA


Abstract
Aims: To explore the potential influence of the Stanford Chronic Disease Self-Management Program (CDSMP) on social support in Parkinson's disease (PD). Methods: This was a quasi-experimental mixed methods design. Volunteers with PD (n = 27) and care partners (n = 6) completed the CDSMP, questionnaires of social support and self-management outcomes, and an interview about social support in relation to CDSMP participation. PD participants (n = 19) who did not participate in the CDSMP completed the questionnaires for quantitative comparison purposes. Results: Regarding the quantitative data, there were no significant effects of CDSMP participation on social support questionnaire scores; however, there were some positive correlations between changes in social support and changes in self-management outcomes from pre- to post-CDSMP participation. Three qualitative themes emerged from the interviews: lack of perceived change in amount and quality of social support, positive impact on existing social networks, and benefit from participating in a supportive PD community. Conclusions: Although participants did not acknowledge major changes in social support, there were some social support-related benefits of CDSMP participation for PD participants and care partners. These findings provide a starting point for more in-depth studies of social support and self-management in this population. © 2017 Taylor & Francis Group, LLC


Author Keywords
caregiving;  Parkinson's disease;  self-management;  Social support


Document Type: Article in Press
Source: Scopus

 

4) 

Elsamadicy, A.A.a b , Chongsathidkiet, P.a b c , Desai, R.d , Woroniecka, K.a b c , Farber, S.H.a b , Fecci, P.E.a b c , Sampson, J.H.a b c 
Prospect of rindopepimut in the treatment of glioblastoma
(2017) Expert Opinion on Biological Therapy, 17 (4), pp. 507-513. 

DOI: 10.1080/14712598.2017.1299705


a Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, NC, United States
b The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, United States
c Department of Pathology, Duke University Medical Center, Durham, NC, United States
d Department of Neurosurgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United States


Abstract
Introduction: Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain–glioblastoma (GBM). Areas covered: The EGFRvIII mutation introduces an 801 base pair in-frame deletion of the extracellular domain of the transmembrane tyrosine kinase, resulting in constitutive kinase activity, amplification of cell growth, and inhibition of apoptosis. Rindopepimut contains a 14mer amino acid peptide spanning the EGFRvIII mutation site that is conjugated to keyhole limpet hemocyanin (KLH). The EGFRvIII neoantigen is exclusively present on GBM cells, providing rindopepimut tumor-specific activity. The authors review rindopepimut’s clinical efficacy, administration, safety, and prospects in the treatment of GBM. Expert opinion: Rindopepimut showed clinical benefit and significant efficacy in phase II clinical trials, including as part of a multi-immunotherapy approach. A phase III clinical trial was terminated early, however, as it was deemed likely the study would fail to meet its primary endpoint. Longer term and sub-group analyses will be necessary to better understand rindopepimut’s future role in GBM therapy. © 2017 Informa UK Limited, trading as Taylor & Francis Group.


Author Keywords
clinical trials;  EGFRvIII;  Glioblastoma;  immunotherapy;  peptide vaccine;  rindopepimut


Document Type: Article
Source: Scopus

 

5) 

Hughes, A.E.O., Enright, J.M., Myers, C.A., Shen, S.Q., Corbo, J.C.
Cell Type-Specific Epigenomic Analysis Reveals a Uniquely Closed Chromatin Architecture in Mouse Rod Photoreceptors
(2017) Scientific Reports, 7, art. no. 43184, . 

DOI: 10.1038/srep43184


Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MI, United States


Abstract
Rod photoreceptors are specialized neurons that mediate vision in dim light and are the predominant photoreceptor type in nocturnal mammals. The rods of nocturnal mammals are unique among vertebrate cell types in having an â € inverted' nuclear architecture, with a dense mass of heterochromatin in the center of the nucleus rather than dispersed clumps at the periphery. To test if this unique nuclear architecture is correlated with a unique epigenomic landscape, we performed ATAC-seq on mouse rods and their most closely related cell type, cone photoreceptors. We find that thousands of loci are selectively closed in rods relative to cones as well as >60 additional cell types. Furthermore, we find that the open chromatin profile of photoreceptors lacking the rod master regulator Nrl is nearly indistinguishable from that of native cones, indicating that Nrl is required for selective chromatin closure in rods. Finally, we identified distinct enrichments of transcription factor binding sites in rods and cones, revealing key differences in the cis-regulatory grammar of these cell types. Taken together, these data provide insight into the development and maintenance of photoreceptor identity, and highlight rods as an attractive system for studying the relationship between nuclear organization and local changes in gene regulation.


Document Type: Article
Source: Scopus

 

6) 

Ramsey,, A.T., Phda , Baumann, A.b , Patterson Silver Wolf, D.b , Yan, Y.c , Cooper, B.d , Proctor, E.b 
The need for data-informed clinical supervision in substance use disorder treatment
(2017) Journal of Addictive Diseases, pp. 1-10. Article in Press. 

DOI: 10.1080/10550887.2017.1291051


a Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
b Brown School of Social Work, Washington University, St. Louis, Missouri, USA
c Division of Public Health Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
d Institute for Public Health, Washington University, St. Louis, Missouri, USA


Abstract
Effective clinical supervision is necessary for high-quality care in community-based substance use disorder treatment settings, yet little is known about current supervision practices. Some evidence suggests that supervisors and counselors differ in their experiences of clinical supervision; however, the impact of this misalignment on supervision quality is unclear. Clinical information monitoring systems may support supervision in substance use disorder treatment, but the potential use of these tools must first be explored. First, the current study examines the extent to which misaligned supervisor–counselor perceptions impact supervision satisfaction and emphasis on evidence-based treatments. This study also reports on formative work to develop a supervision-based clinical dashboard, an electronic information monitoring system and data visualization tool providing real-time clinical information to engage supervisors and counselors in a coordinated and data-informed manner, help align supervisor–counselor perceptions about supervision, and improve supervision effectiveness. Clinical supervisors and frontline counselors (N = 165) from five Midwestern agencies providing substance abuse services completed an online survey using Research Electronic Data Capture software, yielding a 75% response rate. Valid quantitative measures of supervision effectiveness were administered, along with qualitative perceptions of a supervision-based clinical dashboard. Through within-dyad analyses, misalignment between supervisor and counselor perceptions of supervision practices was negatively associated with satisfaction of supervision and reported frequency of discussing several important clinical supervision topics, including evidence-based treatments and client rapport. Participants indicated the most useful clinical dashboard functions and reported important benefits and challenges to using the proposed tool. Clinical supervision tends to be largely an informal and unstructured process in substance abuse treatment, which may compromise the quality of care. Clinical dashboards may be a well-targeted approach to facilitate data-informed clinical supervision in community-based treatment agencies. © 2017 Taylor & Francis Group, LLC


Author Keywords
clinical informatics;  service quality;  substance use disorder treatment;  Supervision


Document Type: Article in Press
Source: Scopus

 

7) 

Kharasch, E.D.a b c 
Current Concepts in Methadone Metabolism and Transport
(2017) Clinical Pharmacology in Drug Development, 6 (2), pp. 125-134. Cited 1 time.

DOI: 10.1002/cpdd.326


a Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Biochemistry and Biophysics, Washington University in St. Louis, St. Louis, MO, United States
c The Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University in St. Louis School of Medicine, St. Louis, MO, United States


Abstract
Methadone is a cornerstone therapy for opioid addiction and a public health strategy for HIV/AIDS and hepatitis C reduction. Methadone is also used for acute and chronic pain. As use for chronic pain has grown, so too have adverse events. Constitutive and acquired (drug interactions) inter- and intraindividual variability in methadone pharmacokinetics and pharmacodynamics confounds reliable clinical use. Identification of enzymes and transporters responsible for methadone disposition has been a long-sought ideal. Initial in vitro studies identified CYP3A4 as metabolizing methadone. Subsequently, by extrapolation, CYP3A4 was long assumed to be responsible for clinical methadone disposition. However, CYP2B6 is also a major catalyst of methadone metabolism in vitro. It has now been unequivocally established that CYP2B6, not CYP3A4, is the principal determinant of methadone metabolism, clearance, elimination, and plasma concentrations in humans. Methadone disposition is susceptible to inductive and inhibitory drug interactions. CYP2B6 genetics also influences methadone metabolism and clearance, which were diminished in CYP2B6*6 carriers and increased in CYP2B6*4 carriers. CYP2B6 genetics can explain, in part, interindividual variability in methadone metabolism and clearance. Thus, both constitutive variability due to CYP2B6 genetics, and CYP2B6-mediated drug interactions, can alter methadone disposition, clinical effect, and drug safety. Methadone is not a substrate for major influx or efflux transporters. © 2017, The American College of Clinical Pharmacology


Author Keywords
CYP2B6;  CYP3A4;  EDDP;  methadone;  P-glycoprotein


Document Type: Article
Source: Scopus

 

8) 

Weidler, B.J., Abrams, R.A.
Simple actions influence pop-out search
(2017) Visual Cognition, pp. 1-14. Article in Press. 

DOI: 10.1080/13506285.2017.1289996


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


Abstract
Recent research has revealed that a simple action (pressing a computer key) produced in response to a visual object prioritizes features of that object in subsequent visual search. The effects of simple action, however, have only been studied with search displays that required serial search. Here we explored whether simple actions have an effect when the target in visual search is always a salient singleton. Participants viewed a coloured shape at the beginning of each trial, and sometimes they acted (pressed the space bar) in response to it. In the subsequent search task, after acting (but not after viewing), the previously-seen colour affected search performance even though the target was always a salient singleton and the colour was uninformative. The results reveal that prior action can interact with bottom-up salience during search. Implications for our understanding of both visual search and repetition priming are discussed. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
action and perception;  Action effect;  repetition priming;  visual search


Document Type: Article in Press
Source: Scopus

 

9) 

Glowinski, A.L., Rosen, M.S.
Prevention targets for child and adolescent depression
(2017) JAMA Psychiatry, 74 (2), pp. 160-161. 

DOI: 10.1001/jamapsychiatry.2016.3160


Division of Child and Adolescent Psychiatry, Department of Psychiatry, Washington University, School of Medicine in St. Louis, 4444 Forrest Pkwy, St. Louis, MO, United States


Document Type: Note
Source: Scopus

 

10) 

Cavazos-Rehg, P.A., Krauss, M.J., Sowles, S.J., Connolly, S., Rosas, C., Bharadwaj, M., Grucza, R., Bierut, L.J.
An analysis of depression, self-harm, and suicidal ideation content on Tumblr
(2017) Crisis, 38 (1), pp. 44-52. 

DOI: 10.1027/0227-5910/a000409


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


Abstract
Background: Social networking about depression can be indicative of self-reported depression and/or can normalize risk behaviors such as self-harm and suicidal ideation. Aim: To gain a better understanding of the depression, self-harm, and suicidal content that is being shared on Tumblr. Method: From April 16 to May 10, 2014, 17 popular depression-related Tumblr accounts were monitored for new posts and engagement with other Tumblr users. A total of 3,360 posts were randomly selected from all historical posts from these accounts and coded based on themes ascertained by the research team. Results: The 17 Tumblr accounts posted a median number of 185 posts (range = 0-2,954). Content was engaged with (i.e., re-blogged or liked) a median number of 1,677,362 times (range = 0-122,186,504). Of the 3,360 randomly selected posts, 2,739 (82%) were related to depression, suicide, or self-harm. Common themes were self-loathing (412, 15%), loneliness/feeling unloved (405, 15%), self-harm (407, 15%), and suicide (372, 14%). Conclusion: This study takes an important first step at better understanding the displayed depression-related references on Tumblr. The findings signal a need for suicide prevention efforts to intervene on Tumblr and use this platform in a strategic way, given the depression and suicidal content that was readily observed on Tumblr. © 2016 Hogrefe Publishing.


Author Keywords
Adolescent;  Depression;  Self-injurious behavior;  Social media;  Suicidal ideation


Document Type: Article
Source: Scopus

 

11) 

Firszt, J.B., Reeder, R.M., Holden, L.K.
Unilateral Hearing Loss: Understanding Speech Recognition and Localization Variability - Implications for Cochlear Implant Candidacy
(2017) Ear and Hearing, 38 (2), pp. 159-173. 

DOI: 10.1097/AUD.0000000000000380


Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, United States


Abstract
Objectives: At a minimum, unilateral hearing loss (UHL) impairs sound localization ability and understanding speech in noisy environments, particularly if the loss is severe to profound. Accompanying the numerous negative consequences of UHL is considerable unexplained individual variability in the magnitude of its effects. Identification of covariables that affect outcome and contribute to variability in UHLs could augment counseling, treatment options, and rehabilitation. Cochlear implantation as a treatment for UHL is on the rise yet little is known about factors that could impact performance or whether there is a group at risk for poor cochlear implant outcomes when hearing is near-normal in one ear. The overall goal of our research is to investigate the range and source of variability in speech recognition in noise and localization among individuals with severe to profound UHL and thereby help determine factors relevant to decisions regarding cochlear implantation in this population. Design: The present study evaluated adults with severe to profound UHL and adults with bilateral normal hearing. Measures included adaptive sentence understanding in diffuse restaurant noise, localization, roving-source speech recognition (words from 1 of 15 speakers in a 140° arc), and an adaptive speech-reception threshold psychoacoustic task with varied noise types and noise-source locations. There were three age-sex-matched groups: UHL (severe to profound hearing loss in one ear and normal hearing in the contralateral ear), normal hearing listening bilaterally, and normal hearing listening unilaterally. Results: Although the normal-hearing-bilateral group scored significantly better and had less performance variability than UHLs on all measures, some UHL participants scored within the range of the normal-hearing-bilateral group on all measures. The normal-hearing participants listening unilaterally had better monosyllabic word understanding than UHLs for words presented on the blocked/deaf side but not the open/hearing side. In contrast, UHLs localized better than the normal-hearing unilateral listeners for stimuli on the open/hearing side but not the blocked/deaf side. This suggests that UHLs had learned strategies for improved localization on the side of the intact ear. The UHL and unilateral normal-hearing participant groups were not significantly different for speech in noise measures. UHL participants with childhood rather than recent hearing loss onset localized significantly better; however, these two groups did not differ for speech recognition in noise. Age at onset in UHL adults appears to affect localization ability differently than understanding speech in noise. Hearing thresholds were significantly correlated with speech recognition for UHL participants but not the other two groups. Conclusions: Auditory abilities of UHLs varied widely and could be explained only in part by hearing threshold levels. Age at onset and length of hearing loss influenced performance on some, but not all measures. Results support the need for a revised and diverse set of clinical measures, including sound localization, understanding speech in varied environments, and careful consideration of functional abilities as individuals with severe to profound UHL are being considered potential cochlear implant candidates. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Author Keywords
Cochlear Implant;  Localization;  Speech recognition;  Unilateral hearing loss


Document Type: Conference Paper
Source: Scopus

 

12) 

Jun, G.R.a b , Chung, J.b , Mez, J.c , Barber, R.d , Beecham, G.W.e , Bennett, D.A.f , Buxbaum, J.D.g h i , Byrd, G.S.j, Carrasquillo, M.M.k , Crane, P.K.l , Cruchaga, C.m n , De Jager, P.o p , Ertekin-Taner, N.k , Evans, D.q , Fallin, M.D.r, Foroud, T.M.s , Friedland, R.P.t , Goate, A.M.g , Graff-Radford, N.R.k , Hendrie, H.u v , Hall, K.S.v w , Hamilton-Nelson, K.L.e , Inzelberg, R.x , Kamboh, M.I.y , Kauwe, J.S.K.z , Kukull, W.A.aa ab , Kunkle, B.W.e , Kuwano, R.ac , Larson, E.B.p ad , Logue, M.W.b f ae , Manly, J.J.af ag , Martin, E.R.e , Montine, T.J.ah , Mukherjee, S.l , Naj, A.ai , Reiman, E.M.aj ak al am , Reitz, C.an ao ap , Sherva, R.b , St. George-Hyslop, P.H.aq ar , Thornton, T.l , Younkin, S.G.k, Vardarajan, B.N.af ag an , Wang, L.-S.aj , Wendlund, J.R.as , Winslow, A.R.as , Haines, J.at , Mayeux, R.af ag an ao ap, Pericak-Vance, M.A.e , Schellenberg, G.aj , Lunetta, K.L.au , Farrer, L.A.b c au av aw 
Transethnic genome-wide scan identifies novel Alzheimer's disease loci
(2017) Alzheimer's and Dementia, . Article in Press. 

DOI: 10.1016/j.jalz.2016.12.012


a Neurogenetics and Integrated Genomics, Andover Innovative Medicines Institute, Eisai Inc, Andover, MA, USA
b Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA
c Department of Neurology, Boston University Schools of Medicine, Boston, MA, USA
d Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA
e The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA
f Department of Neurological Sciences and Rush Alzheimer's Disease Center, Chicago, IL, USA
g Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA
h Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
i Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA
j Department of Biology, North Carolina A and T State University, Greensboro, NC, USA
k Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
l Department of Medicine, University of Washington, Seattle, WA, USA
m Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, USA
n Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
o Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology and Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
p Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
q Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA
r Department of Mental Health, Johns Hopkins University School of Medicine, Baltimore, MD, USA
s Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA
t Department of Neurology, University of Louisville, Louisville, KY, USA
u Department of Psychiatry, Indiana University, Indianapolis, IN, USA
v Regenstrief Institute, Inc, Indianapolis, IN, USA
w Department of Medicine, Indiana University, Indianapolis, IN, USA
x Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
y University of Pittsburgh Alzheimer's Disease Research Center and Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
z Department of Biology, Brigham Young University, Provo, UT, USA
aa Department of Epidemiology, University of Washington, Seattle, WA, USA
ab National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA
ac Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
ad Group Health, Group Health Research Institute, Seattle, WA, USA
ae National Center for PTSD, Behavioral Science Division, Boston VA Healthcare System, Boston, MA, USA
af The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA
ag The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA
ah Department of Pathology, Stanford University, Stanford, CA, USA
ai Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
aj Arizona Alzheimer's Consortium, Phoenix, AZ, USA
ak Department of Psychiatry, University of Arizona, Phoenix, AZ, USA
al Banner Alzheimer's Institute, Phoenix, AZ, USA
am Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA
an The Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
ao The Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA
ap The Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
aq Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Canada
ar Cambridge Institute for Medical Research and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
as PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, MA, USA
at Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
au Department of Biostatistics, Boston University Schools of Public Health, Boston, MA, USA
av Department of Ophthalmology, Boston University Schools of Medicine, Boston, MA, USA
aw Department of Epidemiology, Boston University Schools of Public Health, Boston, MA, USA


Abstract
Introduction: Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods: We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results: Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P &lt; 5 × 10-8) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE e(open)4 allele with NFIC SNP. We also obtained GWS evidence (P &lt; 2.7 × 10-6) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10-6). Discussion: Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci. © 2017 The Authors.


Author Keywords
Alzheimer's disease;  APOE interaction;  Genome-wide association;  Transethnic


Document Type: Article in Press
Source: Scopus

 

13) 

Bogdan, R.a , Salmeron, B.J.c , Carey, C.E.a , Agrawal, A.b , Calhoun, V.D.d e f , Garavan, H.g , Hariri, A.R.h , Heinz, A.i , Hill, M.N.j , Holmes, A.k , Kalin, N.H.m n o , Goldman, D.l 
Imaging Genetics and Genomics in Psychiatry: A Critical Review of Progress and Potential
(2017) Biological Psychiatry, . Article in Press. 

DOI: 10.1016/j.biopsych.2016.12.030


a BRAIN Lab, Department of Psychological and Brain Sciences, St. Louis, Missouri
b Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri
c Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland
d Mind Research Network and Lovelace Biomedical and Environmental Research Institute, University of New Mexico, Albuquerque, New Mexico
e Departments of Psychiatry and Neuroscience, University of New Mexico, Albuquerque, New Mexico
f Electronic and Computer Engineering, University of New Mexico, Albuquerque, New Mexico
g Department of Psychiatry, University of Vermont, Burlington, Vermont
h Laboratory of NeuroGenetics, Department of Psychology and Neuroscience, Duke University, Durham, North Carolina
i Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany
j Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy and Psychiatry, University of Calgary, Calgary, Alberta, Canada
k Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
l Laboratory of Neurogenetics, Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
m Department of Psychiatry, University of Wisconsin, Madison, Wisconsin
n Neuroscience Training Program (NHK, RK, PHR, DPMT, MEE), University of Wisconsin, Madison, Wisconsin
o Wisconsin National Primate Research Center (NHK, MEE), Madison, Wisconsin


Abstract
Imaging genetics and genomics research has begun to provide insight into the molecular and genetic architecture of neural phenotypes and the neural mechanisms through which genetic risk for psychopathology may emerge. As it approaches its third decade, imaging genetics is confronted by many challenges, including the proliferation of studies using small sample sizes and diverse designs, limited replication, problems with harmonization of neural phenotypes for meta-analysis, unclear mechanisms, and evidence that effect sizes may be more modest than originally posited, with increasing evidence of polygenicity. These concerns have encouraged the field to grow in many new directions, including the development of consortia and large-scale data collection projects and the use of novel methods (e.g., polygenic approaches, machine learning) that enhance the quality of imaging genetic studies but also introduce new challenges. We critically review progress in imaging genetics and offer suggestions and highlight potential pitfalls of novel approaches. Ultimately, the strength of imaging genetics and genomics lies in their translational and integrative potential with other research approaches (e.g., nonhuman animal models, psychiatric genetics, pharmacologic challenge) to elucidate brain-based pathways that give rise to the vast individual differences in behavior as well as risk for psychopathology. © 2017 Society of Biological Psychiatry.


Author Keywords
Candidate;  Genetics;  Genomics;  Imaging;  MRI;  Neurogenetics;  Polygenic


Document Type: Article in Press
Source: Scopus

 

March 5, 2017

Hacker, C.D.a , Snyder, A.Z.b c , Pahwa, M.a , Corbetta, M.c , Leuthardt, E.C.a 
Frequency-specific electrophysiologic correlates of resting state fMRI networks
(2017) NeuroImage, 149, pp. 446-457. 

DOI: 10.1016/j.neuroimage.2017.01.054


a Department of Neurosurgery, Washington University School of Medicine, Campus Box 8225, United States
b Department of Radiology, Washington University School of Medicine, Campus Box 8225, United States
c Department of Neurology, Washington University School of Medicine, Campus Box 8225, United States


Abstract
Resting state functional MRI (R-fMRI) studies have shown that slow (<0.1 Hz), intrinsic fluctuations of the blood oxygen level dependent (BOLD) signal are temporally correlated within hierarchically organized functional systems known as resting state networks (RSNs) (Doucet et al., 2011). Most broadly, this hierarchy exhibits a dichotomy between two opposed systems (Fox et al., 2005). One system engages with the environment and includes the visual, auditory, and sensorimotor (SMN) networks as well as the dorsal attention network (DAN), which controls spatial attention. The other system includes the default mode network (DMN) and the fronto-parietal control system (FPC), RSNs that instantiate episodic memory and executive control, respectively. Here, we test the hypothesis, based on the spectral specificity of electrophysiologic responses to perceptual vs. memory tasks (Klimesch, 1999; Pfurtscheller and Lopes da Silva, 1999), that these two large-scale neural systems also manifest frequency specificity in the resting state. We measured the spatial correspondence between electrocorticographic (ECoG) band-limited power (BLP) and R-fMRI correlation patterns in awake, resting, human subjects. Our results show that, while gamma BLP correspondence was common throughout the brain, theta (4–8 Hz) BLP correspondence was stronger in the DMN and FPC, whereas alpha (8–12 Hz) correspondence was stronger in the SMN and DAN. Thus, the human brain, at rest, exhibits frequency specific electrophysiology, respecting both the spectral structure of task responses and the hierarchical organization of RSNs. © 2017 The Authors


Document Type: Article
Source: Scopus

 

2) 

Purkait, S.a , Miller, C.A.b , Kumar, A.a , Sharma, V.a , Pathak, P.a , Jha, P.a , Sharma, M.C.a , Suri, V.a , Suri, A.c , Sharma, B.S.c , Fulton, R.S.b , Kale, S.S.c , Dahiya, S.d , Sarkar, C.a 
ATRX in Diffuse Gliomas With its Mosaic/Heterogeneous Expression in a Subset
(2017) Brain Pathology, 27 (2), pp. 138-145. 

DOI: 10.1111/bpa.12364


a Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
b McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India
d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
This study aims (1) to evaluate ATRX expression in different grades and subtypes of gliomas and correlate with other hallmark genetic alterations, (2) to identify and characterize mosaic/heterogeneous staining in gliomas in terms of mutation status. One hundred seventy six cases of glioma were assessed for ATRX immunohistochemistry and subdivided into positive, negative and mosaic/heterogeneous staining patterns. Five cases with heterogeneous staining were further subjected to next generation sequencing. Higher frequency of ATRX immune-negativity was detected in grade II/III astrocytic, oligoastrocytic tumors and secondary glioblastomas (GBMs), while infrequent in primary GBMs and rare in oligodendrogliomas. Loss of expression was significantly associated with IDH1 and/or TP53 mutation, while mutually exclusive with 1p/19q codeletion. Mosaic/heterogeneous staining was detected exclusively in GBMs (21.2%). Two different types of mosaic staining were identified (1) Admixture of positive and negative nuclei or intermixed mosaic and (2) Separate fragments with positive and negative/intermixed mosaic staining. ATRX mutation was identified in 2/5 (40%) cases with mosaic staining while one case showed DAXX mutation. All these cases were characterized by distinctly separate immune-negative and positive/intermixed foci. Hence, it is suggested that cases with heterogeneous staining (especially those with distinctly negative fragments) should be subjected to mutation analysis. © 2016 International Society of Neuropathology


Author Keywords
ATRX;  Glioma;  heterogeneous staining;  mosaic staining


Document Type: Article
Source: Scopus

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

3) 

Sestieri, C.a , Shulman, G.L.b , Corbetta, M.c d 
The contribution of the human posterior parietal cortex to episodic memory
(2017) Nature Reviews Neuroscience, 18 (3), pp. 183-192. 

DOI: 10.1038/nrn.2017.6


a Department of Neuroscience Imaging and Clinical Sciences, Institute of Advanced Biomedical Technologies, University of Chieti, Chieti, Italy
b Department of Neurology, Washington University School of Medicine, United States
c Department of Neuroscience, University of Padua, Padua, Italy
d Department of Neurology Radiology Neuroscience Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The posterior parietal cortex (PPC) is traditionally associated with attention, perceptual decision making and sensorimotor transformations, but more recent human neuroimaging studies support an additional role in episodic memory retrieval. In this Opinion article, we present a functional-anatomical model of the involvement of the PPC in memory retrieval. Parietal regions involved in perceptual attention and episodic memory are largely segregated and often show a push-pull relationship, potentially mediated by prefrontal regions. Moreover, different PPC regions carry out specific functions during retrieval-for example, representing retrieved information, recoding this information based on task demands, or accumulating evidence for memory decisions. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.


Document Type: Review
Source: Scopus

 

4) 

Harrison, E.C.a , McNeely, M.E.a b , Earhart, G.M.a b c 
The feasibility of singing to improve gait in Parkinson disease
(2017) Gait and Posture, 53, pp. 224-229. 

DOI: 10.1016/j.gaitpost.2017.02.008


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


Abstract
Brain regions important for controlling movement are also responsible for rhythmic processing. In Parkinson disease (PD), defective internal timing within the brain has been linked to impaired beat discrimination, and may contribute to a loss of ability to maintain a steady gait rhythm. Less rhythmic gait is inherently less efficient, and this may lead to gait impairment including reduced speed, cadence, and stride length, as well as increased variability. While external rhythmic auditory stimulation (e.g. a metronome beat) is well-established as an effective tool to stabilize gait in PD, little is known about whether self-generated cues such as singing have the same beneficial effect on gait in PD. Thus, we compared gait patterns of 23 people with mild to moderate PD under five cued conditions: uncued, music only, singing only, singing with music, and a verbal dual-task condition. In our single-session study, singing while walking did not significantly alter velocity, cadence, or stride length, indicating that it was not excessively demanding for people with PD. In addition, walking was less variable when singing than during other cued conditions. This was further supported by the comparison between singing trials and a verbal dual-task condition. In contrast to singing, the verbal dual-task negatively affected gait performance. These findings suggest that singing holds promise as an effective cueing technique that may be as good as or better than traditional cueing techniques for improving gait among people with PD. © 2017 Elsevier B.V.


Author Keywords
Cueing;  Gait;  Music;  Parkinson disease;  Singing


Document Type: Article
Source: Scopus

 

5) 

Dimian, A.F.a i , Botteron, K.N.b , Dager, S.R.c , Elison, J.T.d , Estes, A.M.e , Pruett, J.R., Jr.b , Schultz, R.T.f , Zwaigenbaum, L.g , Piven, J.h , Wolff, J.J.a 
Potential Risk Factors for the Development of Self-Injurious Behavior among Infants at Risk for Autism Spectrum Disorder
(2017) Journal of Autism and Developmental Disorders, pp. 1-13. Article in Press. 

DOI: 10.1007/s10803-017-3057-9


a Department of Educational Psychology, University of Minnesota, 56 East River Rd., Minneapolis, MN, United States
b Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
c Department of Radiology, University of Washington, Seattle, WA, United States
d Institute of Child Development, University of Minnesota, Minneapolis, MN, United States
e Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, United States
f Center for Autism Research, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
g Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
h Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States


Abstract
Prevalence of self-injurious behavior (SIB) is as high as 50% among children with autism spectrum disorder (ASD). Identification of risk factors for the development of SIB is critical to early intervention and prevention. However, there is little empirical research utilizing a prospective design to identify early risk factors for SIB. The purpose of this study was to evaluate behavioral characteristics predicting SIB at age 2 years among 235 infants at high familial risk for ASD. Logistic regression results indicated that presence of SIB or proto-SIB and lower developmental functioning at age 12 months significantly predicted SIB at 24 months. A pattern of persistent SIB over this period was associated with a diagnosis of autism and poorer cognitive and adaptive outcomes. © 2017 The Author(s)


Author Keywords
Autism spectrum disorder;  Infants;  Repetitive behavior;  Risk factors;  Self-injurious behavior


Document Type: Article in Press
Source: Scopus

 

6) 

Holleran, L.a , Kim, J.H.a , Gangolli, M.b , Stein, T.c , Alvarez, V.c , McKee, A.c , Brody, D.L.a d 
Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy
(2017) Acta Neuropathologica, 133 (3), pp. 367-380. 

DOI: 10.1007/s00401-017-1686-x


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States
c Center of the Study of Traumatic Encephalopathy, Boston University School of Medicine, Boston, MA, United States
d Hope Center for Neurological Disorders, St. Louis, MO, United States


Abstract
Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = −0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people. © 2017, Springer-Verlag Berlin Heidelberg.


Author Keywords
Chronic traumatic encephalopathy;  Diffusion MRI;  Diffusion tensor imaging;  Fractional anisotropy;  Phosphorylated tau;  Radiological-pathological correlations;  White matter


Document Type: Article
Source: Scopus

 

7) 

Peelle, J.E.
Optical neuroimaging of spoken language
(2017) Language, Cognition and Neuroscience, pp. 1-8. Article in Press. 

DOI: 10.1080/23273798.2017.1290810


Department of Otolaryngology, Washington University in St. Louis, St. Louis, MO, USA


Abstract
In this review, I introduce the historical context and methods of optical neuroimaging, leading to the modern use of functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) to study human brain function. In its most frequent application, optical neuroimaging measures a haemodynamically-mediated signal indirectly related to neural processing, similar to that captured by fMRI. Compared to other approaches to measuring human brain function, optical imaging has many advantages: it is noninvasive, frequently portable, acoustically silent, robust to motion and muscle movement, and appropriate in many situations in which fMRI is not possible (for example, due to implanted medical devices). Challenges include producing a full-brain field of view, homogenous spatial resolution, and accurate source localisation. Experimentally, optical neuroimaging has been used to study phoneme, word, and sentence processing in a variety of paradigms. With continuing technical and methodological improvements, the future of optical neuroimaging is increasingly bright. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
fNIRS;  HD-DOT;  language;  Speech


Document Type: Article in Press
Source: Scopus

 

8) 

Jain, S.V., Zempel, J.M., Srinivasakumar, P., Wallendorf, M., Mathur, A.
Early EEG power predicts MRI injury in infants with hypoxic-ischemic encephalopathy
(2017) Journal of Perinatology, . Article in Press. 

DOI: 10.1038/jp.2016.262


Division of Pediatric and Developmental Neurology, Department of Neurology, Washington University School of Medicine, St Louis, MO, USA


Abstract
Objective:Early identification of infants with hypoxic-ischemic encephalopathy who have adverse outcomes despite neuroprotection with therapeutic hypothermia (TH) is urgently needed. Recent studies have found limited value of amplitude integrated EEG (aEEG) for predicting short-term outcomes in this population. Other quantitative electroencephalography (EEG) variables reflecting EEG amplitude, such as EEG power, could provide early stratification of a high-risk cohort in this population. The aim of the study was to evaluate and compare early EEG power and aEEG as predictors of magnetic resonance imaging (MRI) injury in neonatal hypoxic-ischemic encephalopathy.Study Design:We conducted a retrospective cohort analysis of 78 encephalopathic infants treated with TH between January 2009 and April 2013. About 56 infants had no/mild injury on MRI (group A), whereas 22 had moderate/severe MRI injury (group B). Total EEG power (TEP) and aEEG were obtained soon after initiation of hypothermia and then compared for their ability to predict future MRI injury.Results:TEP, calculated at a mean age of 8.9 h, was significantly higher in infants in group A as compared to group B (71.6±64.8 vs 26.9±65.3, P=0.02). Odds ratios for predicting moderate-severe MRI injury for TEP&lt;10 μV2, TEP&lt;20 μV2, burst Suppression or worse aEEG pattern were 55 (confidence interval (CI) 6.4 to 471), 12.5 (CI 3.8 to 40.7) and 6.7 (CI 2.0 to 19.8), respectively.Conclusion:Early TEP is a reliable predictor of moderate-severe MRI injury in encephalopathic infants undergoing TH and may enable early stratification of infants who may benefit from adjuvant therapeutic interventions.Journal of Perinatology advance online publication, 16 February 2017; doi:10.1038/jp.2016.262. © 2017 Nature America, Inc., part of Springer Nature.


Document Type: Article in Press
Source: Scopus

 

9) 

Sobieski, C.a d , Fitzpatrick, M.J.a d , Mennerick, S.J.a b c 
Differential presynaptic ATP supply for basal and high-demand transmission
(2017) Journal of Neuroscience, 37 (7), pp. 1888-1899. 

DOI: 10.1523/JNEUROSCI.2712-16.2017


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
c Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States
d Washington University School of Medicine, St. Louis, MO, United States


Abstract
The relative contributions of glycolysis and oxidative phosphorylation to neuronal presynaptic energy demands are unclear. In rat hippocampal neurons, ATP production by either glycolysis or oxidative phosphorylation alone sustained basal evoked synaptic transmission for up to 20 min. However, combined inhibition of both ATP sources abolished evoked transmission. Neither action potential propagation failure nor depressed Ca2+ influx explained loss of evoked synaptic transmission. Rather, inhibition of ATP synthesis caused massive spontaneous vesicle exocytosis, followed by arrested endocytosis, accounting for the disappearance of evoked postsynaptic currents. In contrast to its weak effects on basal transmission, inhibition of oxidative phosphorylation alone depressed recovery from vesicle depletion. Local astrocytic lactate shuttling was not required. Instead, either ambient monocarboxylates or neuronal glycolysis was sufficient to supply requisite substrate. In summary, basal transmission can be sustained by glycolysis, but strong presynaptic demands are met preferentially by oxidative phosphorylation, which can be maintained by bulk but not local monocarboxylates or by neuronal glycolysis. © 2017 the authors.


Author Keywords
Astrocyte;  Glutamate;  Glycolysis;  Neuroenergetics;  Presynaptic


Document Type: Article
Source: Scopus

 

10) 

Whitehead, W.E.a , Riva-Cambrin, J.b , Kulkarni, A.V.c , Wellons, J.C., 3rdd , Rozzelle, C.J.e , Tamber, M.S.f , Limbrick, D.D., Jrg , Browd, S.R.h , Naftel, R.P.i , Shannon, C.N.j , Simon, T.D.k , Holubkov, R.l , Illner, A.m , Cochrane, D.D.n , Drake, J.M.o , Luerssen, T.G.p , Oakes, W.J.q , Kestle, J.R.r , for the Hydrocephalus Clinical Research Networks 
Ventricular catheter entry site and not catheter tip location predicts shunt survival: a secondary analysis of 3 large pediatric hydrocephalus studies
(2017) Journal of neurosurgery. Pediatrics, 19 (2), pp. 157-167. 

DOI: 10.3171/2016.8.PEDS16229


a Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
b Division of Neurosurgery, University of Calgary, Alberta, Canada
c Division of Neurosurgery, University of Toronto, Ontario, Canada
d Department of Neurosurgery, Vanderbilt University, Nashville, Tennessee
e Department of Neurosurgery, University of Alabama at Birmingham, Alabama
f Department of Neurosurgery, University of Pittsburgh, Pennsylvania
g Department of Neurosurgery, Washington University, St. Louis, Missouri;
h Departments of 8 Neurosurgery and
i Department of Neurosurgery, Vanderbilt University, Nashville, Tennessee
j Department of Neurosurgery, Vanderbilt University, Nashville, Tennessee
k Pediatrics, University of Washington, Seattle, Washington
l Department of Pediatrics, University of Utah, Salt Lake City, Utah
m Department of Radiology, Baylor College of Medicine, Houston, Texas; and
n Division of Neurosurgery, University of Toronto, Ontario, Canada
o Division of Neurosurgery, University of Toronto, Ontario, Canada
p Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
q Department of Neurosurgery, University of Alabama at Birmingham, Alabama
r Department of Neurosurgery, University of Utah, Salt Lake City, Utah


Abstract
OBJECTIVE Accurate placement of ventricular catheters may result in prolonged shunt survival, but the best target for the hole-bearing segment of the catheter has not been rigorously defined. The goal of the study was to define a target within the ventricle with the lowest risk of shunt failure. METHODS Five catheter placement variables (ventricular catheter tip location, ventricular catheter tip environment, relationship to choroid plexus, catheter tip holes within ventricle, and crosses midline) were defined, assessed for interobserver agreement, and evaluated for their effect on shunt survival in univariate and multivariate analyses. De-identified subjects from the Shunt Design Trial, the Endoscopic Shunt Insertion Trial, and a Hydrocephalus Clinical Research Network study on ultrasound-guided catheter placement were combined (n = 858 subjects, all first-time shunt insertions, all patients < 18 years old). The first postoperative brain imaging study was used to determine ventricular catheter placement for each of the catheter placement variables. RESULTS Ventricular catheter tip location, environment, catheter tip holes within the ventricle, and crosses midline all achieved sufficient interobserver agreement (κ > 0.60). In the univariate survival analysis, however, only ventricular catheter tip location was useful in distinguishing a target within the ventricle with a survival advantage (frontal horn; log-rank, p = 0.0015). None of the other catheter placement variables yielded a significant survival advantage unless they were compared with catheter tips completely not in the ventricle. Cox regression analysis was performed, examining ventricular catheter tip location with age, etiology, surgeon, decade of surgery, and catheter entry site (anterior vs posterior). Only age (p < 0.001) and entry site (p = 0.005) were associated with shunt survival; ventricular catheter tip location was not (p = 0.37). Anterior entry site lowered the risk of shunt failure compared with posterior entry site by approximately one-third (HR 0.65, 95% CI 0.51-0.83). CONCLUSIONS This analysis failed to identify an ideal target within the ventricle for the ventricular catheter tip. Unexpectedly, the choice of an anterior versus posterior catheter entry site was more important in determining shunt survival than the location of the ventricular catheter tip within the ventricle. Entry site may represent a modifiable risk factor for shunt failure, but, due to inherent limitations in study design and previous clinical research on entry site, a randomized controlled trial is necessary before treatment recommendations can be made.


Author Keywords
CSF shunts;  ESIT = Endoscopic Shunt Insertion Trial;  HCRN = Hydrocephalus Clinical Research Network;  hydrocephalus;  IVH = intraventricular hemorrhage;  pediatric;  SDT = Shunt Design Trial;  shunt entry site;  ventricular catheter


Document Type: Article
Source: Scopus

 

11) 

Limbrick, D.D., Jr.a b , Baksh, B.a , Morgan, C.D.c , Habiyaremye, G.a , McAllister, J.P., IIa , Inder, T.E.d , Mercer, D.a , Holtzman, D.M.e , Strahle, J.a b , Wallendorf, M.J.f , Morales, D.M.a 
Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus
(2017) PLoS ONE, 12 (2), art. no. e0172353, . 

DOI: 10.1371/journal.pone.0172353


a Department of Neurological Surgery, Washington University in St. Louis, School of Medicine, Saint Louis, MO, United States
b Department of Pediatrics, Washington University in St. Louis, School of Medicine, Saint Louis, MO, United States
c Barrow Neurological Institute, Phoenix, AZ, United States
d Department of Pediatric, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
e Department of Neurology, Washington University in St. Louis, School of Medicine, Saint Louis, MO, United States
f Department of Biostatistics, Washington University in Saint Louis, School of Medicine, Saint Louis, MO, United States


Abstract
Introduction Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value. Methods CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC. Results CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p&lt;0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC. Conclusions CSF proteins such as sAPPα and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment. © 2017 Limbrick 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

 

12) 

Jeong, A.a , Strahle, J.b , Vellimana, A.K.c , Limbrick, D.D., Jrd , Smyth, M.D.e , Bertrand, M.f 
Hemispherotomy in children with electrical status epilepticus of sleep
(2017) Journal of neurosurgery. Pediatrics, 19 (1), pp. 56-62. 

DOI: 10.3171/2016.8.PEDS16319


a Departments of 1 Neurology and
b Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
c Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
d Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
e Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
f Departments of 1 Neurology and


Abstract
OBJECTIVE Electrical status epilepticus of sleep (ESES) is a rare electrographic pattern associated with global regression, which is often poorly responsive to traditional epilepsy treatments and can have a devastating and permanent neurocognitive outcome. The authors analyzed clinical, electroencephalographic, and neuropsychological outcomes in 9 patients with refractory ESES treated with functional hemispherotomy to illustrate the wide clinical spectrum associated with the disease and explore the role of hemispherotomy in its treatment. METHODS During the period between 2003 and 2015, 80 patients underwent hemispherotomy at the authors' institution. Video electroencephalography (EEG) reports were reviewed for ESES or continuous spikes and waves during sleep (CSWS). Patients with preoperative ESES (> 85% slow-wave sleep occupied by spike waves), a unilateral structural lesion amenable to surgery, and more than 6 months of follow-up data were included in the analysis. Clinical data, EEG recordings, neuropsychological testing, and parental and clinician reports were retrospectively reviewed. RESULTS Nine patients were eligible for study inclusion. Age at seizure onset ranged from birth to 4.2 years (mean 1.9 years), age at ESES diagnosis ranged from 3.5 to 8.8 years (mean 6.0 years), and age at hemispherotomy ranged from 3.7 to 11.5 years (mean 6.8 years). All patients had drug-resistant epilepsy. The duration of epilepsy prior to hemispherotomy ranged from 2.7 to 8.9 years (mean ± SD, 5.0 ± 2.2 years). Engel Class I seizure outcome was observed in all 9 children, with a mean follow-up of 3.0 years (range 0.5-6.1 years). Hemispherotomy terminated ESES in 6 of 6 patients with available postoperative sleep EEG. All children had preoperative neuropsychological impairments. Developmental regression was halted postoperatively, but none of the children returned to their original pre-ESES baseline. Four children demonstrated academic gains, 2 of whom transitioned to mainstream classes. CONCLUSIONS Children with drug-resistant ESES and a unilateral structural lesion should be evaluated for hemispherotomy as they may experience the cessation of seizures, termination of ESES, and improvement in neuropsychological status.


Author Keywords
continuous spikes and waves during sleep;  CSWS;  CSWS = continuous spikes and waves during sleep;  EEG = electroencephalography;  electrical status epilepticus of sleep;  epilepsy surgery;  ESES;  ESES = electrical status epilepticus of sleep;  FSIQ = Full Scale IQ;  PIQ = Performance IQ;  VIQ = Verbal IQ;  VMI = visual-motor integration;  VNS = vagus nerve stimulator;  WPPSI = Wechsler Preschool and Primary Scale of Intelligence


Document Type: Article
Source: Scopus

 

13) 

Ott, B.R.a b , Jones, R.N.a b c , Noto, R.B.a d , Yoo, D.C.a d , Snyder, P.J.a b , Bernier, J.N.b , Carr, D.B.e f g , Roe, C.M.e f 
Brain amyloid in preclinical Alzheimer's disease is associated with increased driving risk
(2017) Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 6, pp. 136-142. 

DOI: 10.1016/j.dadm.2016.10.008


a Department of Neurology, Alpert Medical School of Brown UniversityProvidence, RI, United States
b Department of Neurology, Rhode Island HospitalProvidence, RI, United States
c Department of Psychiatry and Human Behavior, Rhode Island HospitalProvidence, RI, United States
d Department of Diagnostic Imaging, Rhode Island HospitalProvidence, RI, United States
e Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
f Department of Medicine and Neurology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Introduction Postmortem studies suggest that fibrillar brain amyloid places people at higher risk for hazardous driving in the preclinical stage of Alzheimer's disease (AD). Methods We administered driving questionnaires to 104 older drivers (19 AD, 24 mild cognitive impairment, and 61 cognitive normal) who had a recent 18F-florbetapir positron emission tomography scan. We examined associations of amyloid standardized uptake value ratios with driving behaviors: traffic violations or accidents in the past 3 years. Results The frequency of violations or accidents was curvilinear with respect to standardized uptake value ratios, peaking around a value of 1.1 (model r2 = 0.10, P = 002); moreover, this relationship was evident for the cognitively normal participants. Discussion We found that driving risk is strongly related to accumulating amyloid on positron emission tomography, and that this trend is evident in the preclinical stage of AD. Brain amyloid burden may in part explain the increased crash risk reported in older adults. © 2016 The Authors


Author Keywords
Alzheimer's disease;  Assessment of cognitive disorders;  Biomarkers;  Cognitive aging;  Dementia;  Driving;  MCI (mild cognitive impairment)


Document Type: Article
Source: Scopus

 

14) 

Banks, G., Hadenfeldt, K., Janoch, M., Manning, C., Ramos, K., Patterson Silver Wolf, D.A.
Gun violence and substance abuse
(2017) Aggression and Violent Behavior, . Article in Press. 

DOI: 10.1016/j.avb.2017.02.002


Washington University in St Louis, Brown School of Social Work, 1 Brookings Drive, Campus Box 1196, St Louis, MO 63130, United States


Abstract
Gun violence and substance abuse are prevalent, widespread public health issues that have recently received a great deal of media and political attention. In order to better understand how these phenomena are linked, this paper aims to explore the relationship between the two. First, it will describe the phenomena of gun violence and substance abuse individually. Next, this paper will detail the intersection of gun violence and substance abuse, including shared antecedents, the effect of intoxication on gun violence, and the effect of criminalization of drug use on gun violence. Finally, it will address treatment and policy recommendations. © 2017.


Author Keywords
Gun violence;  Intoxication;  Substance abuse


Document Type: Article in Press
Source: Scopus