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Office of Neuroscience Research > Resources and Facilities > WUSTL Neuroscience Publications for the week > Weekly Neuroscience Publications - Archives > Neuroscience Publications Archive - October 2016

Neuroscience Publications Archive - October 2016

October 27, 2016

1) 

Gorman, K.M.a , Lynch, S.A.b c , Schneider, A.d , Grange, D.K.e , Williamson, K.A.f , FitzPatrick, D.R.f , King, M.D.a b
Status dystonicus in two patients with SOX2-anophthalmia syndrome and nonsense mutations
(2016) American Journal of Medical Genetics, Part A, 170 (11), pp. 3048-3050. 

DOI: 10.1002/ajmg.a.37849


a Department of Neurology and Clinical Neurophysiology, Temple Street Children's University Hospital, Dublin 1, Ireland
b Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 1, Ireland
c Clinical Genetics, Temple Street Children's University Hospital, Dublin 1, Ireland
d Genetics Division, Einstein Medical Center, Philadelphia, PA, United States
e Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
f Medical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom


Author Keywords
SOX2-Anophthalmia s;  status dystonicus;  yndrome


Document Type: Letter
Source: Scopus




2) 

Holden, L.K., Firszt, J.B., Reeder, R.M., Uchanski, R.M., Dwyer, N.Y., Holden, T.A.
Factors Affecting Outcomes in Cochlear Implant Recipients Implanted With a Perimodiolar Electrode Array Located in Scala Tympani
(2016) Otology and Neurotology, . Article in Press. 

DOI: 10.1097/MAO.0000000000001241


Department of Otolaryngology Head and Neck Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri


Abstract
OBJECTIVE:: To identify primary biographic and audiologic factors contributing to cochlear implant (CI) performance variability in quiet and noise by controlling electrode array type and electrode position within the cochlea. BACKGROUND:: Although CI outcomes have improved over time, considerable outcome variability still exists. Biographic, audiologic, and device-related factors have been shown to influence performance. Examining CI recipients with consistent array type and electrode position may allow focused investigation into outcome variability resulting from biographic and audiologic factors. METHODS:: Thirty-nine adults (40 ears) implanted for at least 6 months with a perimodiolar electrode array known (via computed tomography [CT] imaging) to be in scala tympani participated. Test materials, administered CI only, included monosyllabic words, sentences in quiet and noise, and spectral ripple discrimination. RESULTS:: In quiet, scores were high with mean word and sentence scores of 76 and 87%, respectively; however, sentence scores decreased by an average of 35 percentage points when noise was added. A principal components (PC) analysis of biographic and audiologic factors found three distinct factors, PC1 Age, PC2 Duration, and PC3 Pre-op Hearing. PC1 Age was the only factor that correlated, albeit modestly, with speech recognition in quiet and noise. Spectral ripple discrimination strongly correlated with speech measures. CONCLUSION:: For these recipients with consistent electrode position, PC1 Age was related to speech recognition performance. Consistent electrode position may have contributed to high speech understanding in quiet. Inter-subject variability in noise may have been influenced by auditory/cognitive processing, known to decline with age, and mechanisms that underlie spectral resolution ability. Copyright © 2016 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company


Document Type: Article in Press
Source: Scopus




3) 

Cherry-Allen, K.M.a , Gidday, J.M.b c d e , Lee, J.-M.f , Hershey, T.f g h , Lang, C.E.a f i
Remote Limb Ischemic Conditioning at Two Cuff Inflation Pressures Yields Learning Enhancements in Healthy Adults
(2016) Journal of Motor Behavior, pp. 1-12. Article in Press. 

DOI: 10.1080/00222895.2016.1204268


a Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri
b Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
c Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri
d Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri
e Department of Ophthalmology, Louisiana State University School of Medicine, New Orleans
f Department of Neurology, Washington University School of Medicine, St. Louis, Missouri
g Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
h Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
i Program in Occupational Therapy, Washington University School of Medicine, St. Louis, Missouri


Abstract
The authors tested whether 2 doses of remote limb ischemic conditioning (RLIC), induced via blood pressure cuff inflation, enhanced motor and cognitive learning to an equal extent, and explored a panel of blood biomarkers of RLIC. Thirty-two young adults were randomized to 3 groups and underwent a 7-day protocol of RLIC/sham followed by motor and cognitive training, with follow-up. Both RLIC groups had greater motor learning and a trend toward greater cognitive learning compared with the sham group. RLIC at the lower inflation pressure was as effective as RLIC with the higher inflation pressure. No significant candidate blood biomarkers were found. RLIC could be a well-tolerated method to enhance learning and improve rehabilitation outcomes in people with neurological conditions. 2016 Copyright © Taylor & Francis Group, LLC


Author Keywords
behavioral training;  human learning;  motor learning;  remote limb ischemic conditioning


Document Type: Article in Press
Source: Scopus




4) 

Musgrave, S.a , Morgan, D.b c , Lonsdorf, E.d , Mundry, R.e , Sanz, C.a c
Tool transfers are a form of teaching among chimpanzees
(2016) Scientific Reports, 6, art. no. 34783, . 

DOI: 10.1038/srep34783


a Department of Anthropology, Washington University in Saint Louis, Saint Louis, United States
b Lester E. Fisher Center for the Study and Conservation of Apes, Lincoln Park Zoo, Chicago, United States
c Congo Program, Wildlife Conservation Society, Brazzaville, Congo
d Department of Psychology, Franklin and Marshall College, Lancaster, United States
e Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany


Abstract
Teaching is a form of high-fidelity social learning that promotes human cumulative culture. Although recently documented in several nonhuman animals, teaching is rare among primates. In this study, we show that wild chimpanzees (Pan troglodytes troglodytes) in the Goualougo Triangle teach tool skills by providing learners with termite fishing probes. Tool donors experienced significant reductions in tool use and feeding, while tool recipients significantly increased their tool use and feeding after tool transfers. These transfers meet functional criteria for teaching: they occur in a learner's presence, are costly to the teacher, and improve the learner's performance. Donors also showed sophisticated cognitive strategies that effectively buffered them against potential costs. Teaching is predicted when less costly learning mechanisms are insufficient. Given that these chimpanzees manufacture sophisticated, brush-tipped fishing probes from specific raw materials, teaching in this population may relate to the complexity of these termite-gathering tasks. © 2016 The Author(s).


Document Type: Article
Source: Scopus




5) 

Summers, D.W.a b , Gibson, D.A.b , DiAntonio, A.b c , Milbrandt, J.a c
SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation
(2016) Proceedings of the National Academy of Sciences of the United States of America, 113 (41), pp. E6271-E6280. 

DOI: 10.1073/pnas.1601506113


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


Abstract
Axon injury in response to trauma or disease stimulates a self-destruction program that promotes the localized clearance of damaged axon segments. Sterile alpha and Toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) is an evolutionarily conserved executioner of this degeneration cascade, also known as Wallerian degeneration; however, the mechanism of SARM1-dependent neuronal destruction is still obscure. SARM1 possesses a TIR domain that is necessary for SARM1 activity. In other proteins, dimerized TIR domains serve as scaffolds for innate immune signaling. In contrast, dimerization of the SARM1 TIR domain promotes consumption of the essential metabolite NAD+and induces neuronal destruction. This activity is unique to the SARM1 TIR domain, yet the structural elements that enable this activity are unknown. In this study, we identify fundamental properties of the SARM1 TIR domain that promote NAD+loss and axon degeneration. Dimerization of the TIR domain from the Caenorhabditis elegans SARM1 ortholog TIR-1 leads to NAD+loss and neuronal death, indicating these activities are an evolutionarily conserved feature of SARM1 function. Detailed analysis of sequence homology identifies canonical TIR motifs as well as a SARM1-specific (SS) loop that are required for NAD+loss and axon degeneration. Furthermore, we identify a residue in the SARM1 BB loop that is dispensable for TIR activity yet required for injury-induced activation of full-length SARM1, suggesting that SARM1 function requires multidomain interactions. Indeed, we identify a physical interaction between the autoinhibitory N terminus and the TIR domain of SARM1, revealing a previously unrecognized direct connection between these domains that we propose mediates autoinhibition and activation upon injury.


Author Keywords
Axon degeneration;  Cell death;  NAD;  SARM;  Sarmoptosis


Document Type: Article
Source: Scopus




6) 

Cantoni, C.a , Cignarella, F.a , Ghezzi, L.a b , Mikesell, B.a , Bollman, B.a , Berrien-Elliott, M.M.c , Ireland, A.R.c , Fehniger, T.A.c , Wu, G.F.a d e , Piccio, L.a e
Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis
(2016) Acta Neuropathologica, pp. 1-17. Article in Press. 

DOI: 10.1007/s00401-016-1621-6


a Department of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8111, St. Louis, MO, United States
b Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy
c Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
e Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Myeloid-derived cells play important modulatory and effector roles in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells, composed of monocytic (MO) and polymorphonuclear (PMN) fractions, which can suppress T cell activities in EAE. Their role in MS remains poorly characterized. We found decreased numbers of circulating MDSCs, driven by lower frequencies of the MO-MDSCs, and higher MDSC expression of microRNA miR-223 in MS versus healthy subjects. To gain mechanistic insights, we interrogated the EAE model. MiR-223 knock out (miR-223−/−) mice developed less severe EAE with increased MDSC numbers in the spleen and spinal cord compared to littermate controls. MiR-223−/− MO-MDSCs suppressed T cell proliferation and cytokine production in vitro and EAE in vivo more than wild-type MO-MDSCs. They also displayed an increased expression of critical mediators of MDSC suppressive function, Arginase-1(Arg1), and the signal transducer and activator of transcription 3 (Stat3), which herein, we demonstrate being an miR-223 target gene. Consistently, MDSCs from MS patients displayed decreased STAT3 and ARG1 expression compared with healthy controls, suggesting that circulating MDSCs in MS are not only reduced in numbers but also less suppressive. These results support a critical role for miR-223 in modulating MDSC biology in EAE and in MS and suggest potential novel therapeutic applications. © 2016 Springer-Verlag Berlin Heidelberg


Author Keywords
MicroRNA;  MiR-223;  Multiple sclerosis;  Myeloid-derived suppressor cells


Document Type: Article in Press
Source: Scopus




7) 

Whalen, D.J., Belden, A.C., Tillman, R., Barch, D.M., Luby, J.L.
Early Adversity, Psychopathology, and Latent Class Profiles of Global Physical Health From Preschool Through Early Adolescence
(2016) Psychosomatic Medicine, . Article in Press. 

DOI: 10.1097/PSY.0000000000000398


From the Department of Psychiatry (Whalen, Belden, Tillman, Barch, Luby), The Program in Neuroscience (Barch), Department of Psychology (Barch), and Department of Radiology (Barch), Washington University School of Medicine, St. Louis, Missouri.


Abstract
OBJECTIVE: The purpose of the present report was to describe the longitudinal trajectories of physical health beginning during preschool and continuing into early adolescence; explore whether these trajectories were predicted by psychosocial adversity, family income-to-needs ratio, and psychiatric disorders occurring during the preschool period; and determine whether psychiatric disorders mediated these relations. METHODS: Participants included 296 children participating in a longitudinal study of early-onset psychopathology spanning 10 years. Semistructured clinical interviews were conducted with caregivers to determine children's psychiatric diagnoses between ages 3 and 6 years. Caregivers also completed annual assessments of their child's physical health problems (ages 3–13) and reported on the family's income and indicators of psychosocial adversity. RESULTS: Growth mixture modeling revealed 2 trajectories of physical health problems: a stable, low group (n = 199) and a high, increasing group (n = 57) indicating linear increases in physical health problems from ages 3 to 13. Preschool psychiatric diagnoses (Estimate [Est] = 0.05, p < .001), family income-to-needs ratio (Est = −0.01, p = .012), and psychosocial adversity (Est = 0.02, p = .015) predicted membership in the high, increasing trajectory of physical health problems. Early-onset psychopathology mediated relations between psychosocial adversity and physical health problems (αβ = 0.31, p = .050) and between income-to-needs ratio and physical health problems (αβ = −0.29, p < .021). CONCLUSIONS: These findings indicate the importance of early indicators of risk: low income-to-needs ratios, high psychosocial adversity, and psychiatric disorders occurring during the preschool period for contributing to increasing physical health problems from preschool through early adolescence. Early-onset psychiatric disorders also mediated relations between psychosocial adversity, income-to-needs ratio, and physical health problems. Copyright © 2016 by American Psychosomatic Society


Document Type: Article in Press
Source: Scopus




8) 

Smithson, L.J., Anastasaki, C., Chen, R., Toonen, J.A., Williams, S.B., Gutmann, D.H.
Contextual signaling in cancer
(2016) Seminars in Cell and Developmental Biology, 58, pp. 118-126. Cited 1 time.

DOI: 10.1016/j.semcdb.2016.06.002


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


Abstract
The formation and maintenance of an organism are highly dependent on the orderly control of cell growth, differentiation, death, and migration. These processes are tightly regulated by signaling cascades in which a limited number of molecules dictate these cellular events. While these signaling pathways are highly conserved across species and cell types, the functional outcomes that result from their engagement are specified by the context in which they are activated. Using the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome as an illustrative platform, we discuss how NF1/RAS signaling can create functional diversity at multiple levels (molecular, cellular, tissue, and genetic/genomic). As such, the ability of related molecules (e.g., K-RAS, H-RAS) to activate distinct effectors, as well as cell type- and tissue-specific differences in molecular composition and effector engagement, generate numerous unique functional effects. These variations, coupled with a multitude of extracellular cues and genomic/genetic changes that each modify the innate signaling properties of the cell, enable precise control of cellular physiology in both health and disease. Understanding these contextual influences is important when trying to dissect the underlying pathogenic mechanisms of cancer relevant to molecularly-targeted therapeutics. © 2016 Elsevier Ltd


Author Keywords
Astrocyte;  Glioma;  mTOR;  Nervous system;  Neuron;  NF1;  RAS


Document Type: Review
Source: Scopus




9) 

Lim, Y.Y.a , Hassenstab, J.b , Cruchaga, C.c , Goate, A.d , Fagan, A.M.b , Benzinger, T.L.S.e , Maruff, P.a f , Snyder, P.J.g , Masters, C.L.a , Allegri, R.h , Chhatwal, J.i j , Farlow, M.R.k , Graff-Radford, N.R.l , Laske, C.m n , Levin, J.o , McDade, E.b , Ringman, J.M.p , Rossor, M.q , Salloway, S.g , Schofield, P.R.r s , Holtzman, D.M.b , Morris, J.C.b , Bateman, R.J.b
BDNF Val66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer's disease
(2016) Brain, 139 (10), pp. 2766-2777. Cited 1 time.

DOI: 10.1093/brain/aww200


a Florey Institute, University of Melbourne, 155 Oak Street, Parkville, VIC, Australia
b Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
d Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
e Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
f Cogstate Ltd., Melbourne, VIC, Australia
g Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, United States
h Ageing and Memory Center, Instituto de Investigaciones Neurologicas Raúl Carrea (FLENI), Buenos Aires, Argentina
i Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
j Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
k Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States
l Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
m German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
n Section for Dementia Research, Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
o Department of Neurology, University of Munich, Munich, Germany
p Memory and Aging Center, Keck School of Medicine, University of Southern CaliforniaCA, United States
q Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, United Kingdom
r Neuroscience Research Australia, Sydney, NSW, Australia
s School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia


Abstract
See Rogaeva and Schmitt-Ulms (doi:10.1093/aww201) for a scientific commentary on this article. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-β-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-β in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) ?4 on these relationships. The Dominantly Inherited Alzheimer Network conducted clinical, neuropsychological, genetic, biomarker and neuroimaging measures at baseline in 131 mutation non-carriers and 143 preclinical autosomal dominant Alzheimer's disease mutation carriers on average 12 years before clinical symptom onset. BDNF genotype data were obtained for mutation carriers (95 Val66 homozygotes, 48 Met66 carriers). Among preclinical mutation carriers, Met66 carriers had worse memory performance, lower hippocampal glucose metabolism and increased levels of cerebrospinal fluid tau and phosphorylated tau (p-tau) than Val66 homozygotes. Cortical amyloid-β and cerebrospinal fluid amyloid-β42 levels were significantly different from non-carriers but did not differ between preclinical mutation carrier Val66 homozygotes and Met66 carriers. There was an effect of APOE on amyloid-β levels, but not cognitive function, glucose metabolism or tau. As in sporadic Alzheimer's disease, the deleterious effects of amyloid-β on memory, hippocampal function, and tau in preclinical autosomal dominant Alzheimer's disease mutation carriers are greater in Met66 carriers. To date, this is the only genetic factor found to moderate downstream effects of amyloid-β in autosomal dominant Alzheimer's disease. © 2016 The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.


Author Keywords
Alzheimer's disease;  amyloid-β;  dementia;  genetics;  tau


Document Type: Article
Source: Scopus




10) 

Dussor, G.a , Cao, Y.-Q.b
TRPM8 and Migraine
(2016) Headache, 56 (9), pp. 1406-1417. 

DOI: 10.1111/head.12948


a School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States
b Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Migraine is among the most common diseases on earth and one of the most disabling, the latter due in large part to poor treatment efficacy. Development of new therapeutics is dependent on the identification of mechanisms contributing to migraine and discovery of targets for new drugs. Numerous genome-wide association studies (GWAS) have implicated the transient receptor-potential M8 (TRPM8) channel in migraine. This channel is predominantly expressed on peripheral sensory neurons and is known as the sensor for cold temperature in cutaneous tissue but is also expressed on deep visceral afferents where cold is not likely a stimulus. Consequently, a number of alternative endogenous agonists have been proposed. Apart from its role in cold sensation, TRPM8 also contributes to cold allodynia after nerve injury or inflammation, and it is necessary for cooling/menthol-based analgesia. How it might contribute to migraine is less clear. The purpose of this review is to discuss the anatomical and physiological mechanisms by which meningeal TRPM8 may play a role in migraine as well as the potential of TRPM8 as a therapeutic target. TRPM8 is expressed on sensory afferents innervating the meninges, and these neurons are subject to developmental changes that may influence their contribution to migraine. As in viscera, meningeal TRPM8 channels are unlikely to be activated by temperature fluctuations and their endogenous ligands remain unknown. Preclinical migraine studies show that activation of meningeal TRPM8 by exogenous agonists can both cause and alleviate headache behaviors, depending on whether other meningeal afferents concurrently receive noxious stimuli. This is reminiscent of the fact that cold can trigger migraine in humans but menthol can also alleviate headache. We propose that both TRPM8 agonists and antagonists may be potential therapeutics, depending on how migraine is triggered in individual patients. In this regard, TRPM8 may be a novel target for personalized medicine in migraine treatment. © 2016 American Headache Society


Author Keywords
dura;  icilin;  meninges;  menthol;  trigeminal;  TRP


Document Type: Review
Source: Scopus




11) 

Chang, M.a b , Womer, F.Y.c , Bai, C.a b , Zhou, Q.b c , Wei, S.a d , Jiang, X.a d , Geng, H.a , Zhou, Y.c , Tang, Y.b c , Wang, F.a b c e
Voxel-based morphometry in individuals at genetic high risk for schizophrenia and patients with schizophrenia during their first episode of psychosis
(2016) PLoS ONE, 11 (10), art. no. e163749, . 

DOI: 10.1371/journal.pone.0163749


a Department of Radiology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
b Brain Function Research Section, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
c Department of Psychiatry, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
d Department of Psychiatry, Washington University, School of Medicine, St. Louis, MI, United States
e Department of Psychiatry, Yale University, School of Medicine, New Haven, CT, United States


Abstract
Background Understanding morphologic changes in vulnerable and early disease state of schizophrenia (SZ) may provide further insight into the development of psychosis. Method Whole brain voxel-based morphometry was performed to identify gray matter (GM) regional differences in 60 individuals with SZ during their first psychotic episode (FE-SZ), 31 individuals at genetic high risk for SZ (GHR-SZ) individuals, and 71 healthy controls. Results Significant differences were found in several regions including the prefrontal cortex, parietal lobe, temporal lobe, hippocampus, occipital lobe, and cerebellum among the three groups (p<0.05, corrected). Compared to the HC group, the FE-SZ group had significantly decreased GM volumes in several regions including the cerebellum, hippocampus, fusiform gyrus, lingual gyrus, supramarginal gyrus, and superior, middle, and inferior temporal gyri and significantly increased GM volumes in the middle frontal gyrus and inferior operculum frontal gyrus (p<0.05). The GHR-SZ group had significant decreases in GM volumes in the supramaginal gyrus, precentral gyrus, and rolandic operculum and significant increases in GM volumes in the cerebellum, fusiform gyrus, middle frontal gyrus, inferior operculum frontal gyrus, and superior, middle, and inferior temporal gyri when compared to the HC group (p<0.05). Compared to the GHR-SZ group, the FE-SZ group had significant decreases in GM volumes in several regions including the cerebellum, fusiform gyrus, supramarginal gyrus, and superior, middle, and inferior temporal gyri (p<0.05). Conclusions The findings herein implicate the involvement of multisensory integration in SZ development and pathophysiology. Additionally, the patterns of observed differences suggest possible indicators of disease, vulnerability, and resiliency in SZ. © 2016 Chang 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) 

Andrus, C.F.
Attention-Deficit/Hyperactivity Disorder: An Update for the Pediatric Primary Care Provider
(2016) Physician Assistant Clinics, 1 (4), pp. 683-699. 

DOI: 10.1016/j.cpha.2016.06.001


University Pediatric Associates, LLC, Washington University School of Medicine, 13001 North Outer Forty Road, Suite 310, St. Louis, MO, United States


Abstract
Attention-deficit/hyperactivity disorder (ADHD) is the most common pediatric neurobehavioral disorder. Most individuals with ADHD have comorbid psychiatric illnesses, such as anxiety, depression, conduct disorder, or oppositional defiant disorder. Pediatric primary care providers are on the frontline for screening, evaluation, diagnosis, and management of childhood and adolescent ADHD. Stimulant medication has been considered first-line therapy for decades and continues to prove its efficacy among appropriately diagnosed patients. Nonstimulant medications and medical nutrition therapy have gained more recognition for either primary or supplemental management for ADHD. This article provides a clinical update on the screening, diagnostic guidelines, and management for pediatric primary care clinicians. © 2016 Elsevier Inc.


Author Keywords
Attention-deficit/hyperactivity disorder;  Medical management of ADHD;  Pediatric mental health;  Stimulant medication


Document Type: Review
Source: Scopus




13) 

De Pasquale, F.a , Della Penna, S.a , Sporns, O.b , Romani, G.L.a , Corbetta, M.c d
A Dynamic Core Network and Global Efficiency in the Resting Human Brain
(2016) Cerebral Cortex, 26 (10), pp. 4015-4033. 

DOI: 10.1093/cercor/bhv185


a Institute for Advanced Biomedical Technologies, Department of Neuroscience, Imaging and Clinical Sciences, G. d'Annunzio University, Chieti, Italy
b Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States
c Departments of Neurology, Radiology, Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO, United States
d ITAB, University of Chieti, Chieti, Italy


Abstract
Spontaneous brain activity is spatially and temporally organized in the absence of any stimulation or task in networks of cortical and subcortical regions that appear largely segregated when imaged at slow temporal resolution with functional magnetic resonance imaging (fMRI). When imaged at high temporal resolution with magneto-encephalography (MEG), these resting-state networks (RSNs) show correlated fluctuations of band-limited power in the beta frequency band (14-25 Hz) that alternate between epochs of strong and weak internal coupling. This study presents 2 novel findings on the fundamental issue of how different brain regions or networks interact in the resting state. First, we demonstrate the existence of multiple dynamic hubs that allow for across-network coupling. Second, dynamic network coupling and related variations in hub centrality correspond to increased global efficiency. These findings suggest that the dynamic organization of across-network interactions represents a property of the brain aimed at optimizing the efficiency of communication between distinct functional domains (memory, sensory-attention, motor). They also support the hypothesis of a dynamic core network model in which a set of network hubs alternating over time ensure efficient global communication in the whole brain. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved.


Author Keywords
betweenness centrality;  brain dynamics;  core network model;  MEG;  resting-state networks


Document Type: Article
Source: Scopus




14) 

Smyser, C.D.a b c , Tam, E.W.Y.d , Chang, T.e , Soul, J.S.f , Miller, S.P.d , Glass, H.C.g h i
Fellowship Training in the Emerging Fields of Fetal-Neonatal Neurology and Neonatal Neurocritical Care
(2016) Pediatric Neurology, 63, pp. 39-44.e3. 

DOI: 10.1016/j.pediatrneurol.2016.06.006


a Department of Neurology, Washington University, St. Louis, Missouri, United States
b Department of Pediatrics, Washington University, St. Louis, Missouri, United States
c Department of Radiology, Washington University, St. Louis, Missouri, United States
d Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Ontario, Canada
e Department of Neurology, Children's National Health System, Washington, DC, United States
f Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States
g Department of Neurology, Benioff Children's Hospital, University of California, San Francisco, California, United States
h Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, California, United States
i Department of Epidemiology and Biostatistics, Benioff Children's Hospital, University of California, San Francisco, California, United States


Abstract
Background Neonatal neurocritical care is a growing and rapidly evolving medical subspecialty, with increasing numbers of dedicated multidisciplinary clinical, educational, and research programs established at academic institutions. The growth of these programs has provided trainees in neurology, neonatology, and pediatrics with increased exposure to the field, sparking interest in dedicated fellowship training in fetal-neonatal neurology. Objectives To meet this rising demand, increasing numbers of training programs are being established to provide trainees with the requisite knowledge and skills to independently deliver care for infants with neurological injury or impairment from the fetal care center and neonatal intensive care unit to the outpatient clinic. This article provides an initial framework for standardization of training across these programs. Results Recommendations include goals and objectives for training in the field; core areas where clinical competency must be demonstrated; training activities and neuroimaging and neurodiagnostic modalities which require proficiency; and programmatic requirements necessary to support a comprehensive and well-rounded training program. Conclusions With consistent implementation, the proposed model has the potential to establish recognized standards of professional excellence for training in the field, provide a pathway toward Accreditation Council for Graduate Medical Education certification for program graduates, and lead to continued improvements in medical and neurological care provided to patients in the neonatal intensive care unit. © 2016 Elsevier Inc.


Author Keywords
education;  fellowship;  fetal neurology;  neonatal neurocritical care;  neonatal neurology;  neonatology;  neurophysiology;  neuroradiology


Document Type: Review
Source: Scopus




15) 

Salzman, G.S.a b c , Ackerman, S.D.d , Ding, C.c , Koide, A.c g , Leon, K.c , Luo, R.e , Stoveken, H.M.f , Fernandez, C.G.c , Tall, G.G.f , Piao, X.e , Monk, K.R.d , Koide, S.c , Araç, D.c
Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains
(2016) Neuron, 91 (6), pp. 1292-1304. 

DOI: 10.1016/j.neuron.2016.08.022


a Biophysical Sciences Program, The University of Chicago, Chicago, IL, United States
b Medical Scientist Training Program, The University of Chicago, Chicago, IL, United States
c Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, United States
d Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
e Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States
f Departments of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, United States
g Perlmutter Cancer Center and Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, NY, United States


Abstract
Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology. © 2016 Elsevier Inc.


Author Keywords
adhesion GPCR;  monobody;  oligodendrocyte development;  protein engineering;  X-ray crystallography


Document Type: Article
Source: Scopus




16) 

Bazyar, S.a , Ramalho, J.b , Eldeniz, C.c , An, H.c d , Lee, Y.Z.a e f g
Comparison of cerebral blood volume and plasma volume in untreated intracranial tumors
(2016) PLoS ONE, 11 (9), art. no. e0161807, . 

DOI: 10.1371/journal.pone.0161807


a Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
b Centro Hospitalar de Lisboa Central, Lisboa, Portugal
c Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States
d Center for Clinical Imaging Research, Washington University in St. Louis, St. Louis, MO, United States
e Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
f Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
g Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States


Abstract
Purpose Plasma volume and blood volume are imaging-derived parameters that are often used to evaluation intracranial tumors. Physiologically, these parameters are directly related, but their two different methods of measurements, T1-dynamic contrast enhanced (DCE)-and T2-dynamic susceptibility contrast (DSC)-MR utilize different model assumptions and approaches. This poses the question of whether the interchangeable use of T1-DCE-MRI derived fractionated plasma volume (vp) and relative cerebral blood volume (rCBV) assessed using DSC-MRI, particularly in glioblastoma, is reliable, and if this relationship can be generalized to other types of brain tumors. Our goal was to examine the hypothetical correlation between these parameters in three most common intracranial tumor types. Methods Twenty-four newly diagnosed, treatment naïve brain tumor patients, who had undergone DCE-and DSC-MRI, were classified in three histologically proven groups: glioblastoma (n = 7), meningioma (n = 9), and intraparenchymal metastases (n = 8). The rCBV was obtained from DSC after normalization with the normal-appearing anatomically symmetrical contralateral white matter. Correlations between these parameters were evaluated using Pearson (r), Spearman's (?) and Kendall's tau-b (τB) rank correlation coefficient. Results The Pearson, Spearman and Kendall's correlation between vp with rCBV were r = 0.193, ? = 0.253 and τB = 0.33 (p-Pearson = 0.326, p-Spearman = 0.814 and p-Kendall = 0.823) in glioblastoma, r =-0.007, ? = 0.051 and τB = 0.135 (p-Pearson = 0.970, p-Spearman = 0.765 and p-Kendall = 0.358) in meningiomas, and r = 0.289, ? = 0.228 and τB = 0.239 (p-Pearson = 0.109, p-Spearman = 0.210 and p-Kendall = 0.095) in metastasis. Conclusion Results indicate that no correlation exists between vp with rCBV in glioblastomas, meningiomas and intraparenchymal metastatic lesions. Consequently, these parameters, as calculated in this study, should not be used interchangeably in either research or clinical practice. © 2016 Bazyar 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




17) 

Xu, P.S., Lee, D., Holy, T.E.
Experience-Dependent Plasticity Drives Individual Differences in Pheromone-Sensing Neurons
(2016) Neuron, 91 (4), pp. 878-892. 

DOI: 10.1016/j.neuron.2016.07.034


Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Different individuals exhibit distinct behaviors, but studying the neuronal basis of individuality is a daunting challenge. Here, we considered this question in the vomeronasal organ, a pheromone-detecting epithelium containing hundreds of distinct neuronal types. Using light-sheet microscopy, we characterized in each animal the abundance of 17 physiologically defined types, altogether recording from half a million sensory neurons. Inter-animal differences were much larger than predicted by chance, and different physiological cell types showed distinct patterns of variability. One neuronal type was present in males and nearly absent in females. Surprisingly, this apparent sexual dimorphism was generated by plasticity, as exposure to female scents or single ligands led to both the elimination of this cell type and alterations in olfactory behavior. That an all-or-none apparent sex difference in neuronal types is controlled by experience—even in a sensory system devoted to “innate” behaviors—highlights the extraordinary role of “nurture” in neural individuality. © 2016 Elsevier Inc.


Document Type: Article
Source: Scopus




18) 

Chapman, C.H.a f , Zhu, T.a , Nazem-Zadeh, M.a g , Tao, Y.b , Buchtel, H.A.c h , Tsien, C.I.a i , Lawrence, T.S.a , Cao, Y.a d e
Diffusion tensor imaging predicts cognitive function change following partial brain radiotherapy for low-grade and benign tumors
(2016) Radiotherapy and Oncology, 120 (2), pp. 234-240. 

DOI: 10.1016/j.radonc.2016.06.021


a Department of Radiation Oncology, University of Michigan, Ann Arbor, United States
b Department of Biostatistics, University of Michigan, Ann Arbor, United States
c Department of Psychiatry, University of Michigan, Ann Arbor, United States
d Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
e Department of Radiology, University of Michigan, Ann Arbor, United States
f Department of Radiation Oncology, University of California San Francisco, United States
g Radiology and Research Administration Departments, Henry Ford Hospital, Detroit, United States
h VA Ann Arbor Healthcare System, Ann Arbor, United States
i Department of Radiation Oncology, Washington University, St. Louis, United States


Abstract
Purpose/objectives Radiation injury to parahippocampal cingulum white matter is associated with cognitive decline. Diffusion tensor imaging (DTI) detects micropathologic changes in white matter. Increased radial diffusion (RD) and decreased axial diffusion (AD) correspond to demyelination and axonal degeneration/gliosis respectively. We aimed to develop a predictive model for radiation-induced cognitive changes based upon DTI changes. Materials/methods Twenty-seven adults with benign or low-grade tumors received partial brain radiation therapy (RT) to a median dose of 54 Gy. Patients underwent DTI before RT, during RT, and at the end of RT. Cognitive testing was performed before RT, and 6 and 18 months after RT. Parahippocampal cingulum white matter was contoured to obtain mean values of AD and RD. Results By univariate analysis, decreasing AD and increasing RD during RT predicted declines in verbal memory and verbal fluency. By multivariate analysis, baseline neurocognitive score was the only clinical variable predicting verbal memory change; no clinical variables predicted verbal fluency change. In a multivariate model, increased RD at the end of RT significantly predicted decline in verbal fluency 18 months after RT. Conclusions Imaging biomarkers of white matter injury contributed to predictive models of cognitive function change after RT. © 2016 Elsevier Ireland Ltd


Author Keywords
Cognitive function;  Glioma;  Late effects;  Magnetic resonance imaging


Document Type: Article
Source: Scopus




19) 

Evangelista, T.a , Weihl, C.C.b , Kimonis, V.c , Lochmüller, H.a , Clemen, C.d , Deshaies, R.e , Evangelista, T.f , Eymard, B.g , Greensmith, L.h , Hilton-Jones, D.i , Kimonis, V.j , Kley, R.k , Lochmüller, H.l , Meyer, H.m , Mozaffar, T.n , Noguchi, S.o , Ralston, S.p , Ridha, B.q , Udd, B.r , Weihl, C.s , Brumhard, M.t , Brumhard, S.u
215th ENMC International Workshop VCP-related multi-system proteinopathy (IBMPFD) 13–15 November 2015, Heemskerk, The Netherlands
(2016) Neuromuscular Disorders, 26 (8), pp. 535-547. 

DOI: 10.1016/j.nmd.2016.05.017


a John Walton Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, United Kingdom
b Neuromuscular Division, Washington University School of Medicine, Saint Louis, MO, United States
c Division of Genetics and Genomic Medicine, University of California – Irvine Medical Centre, Irvine, United States


Document Type: Conference Paper
Source: Scopus




20) 

McDermott, K.B.a b , Gilmore, A.W.a , Nelson, S.M.c d e , Watson, J.M.f , Ojemann, J.G.g
The parietal memory network activates similarly for true and associative false recognition elicited via the DRM procedure
(2016) Cortex, . Article in Press. 

DOI: 10.1016/j.cortex.2016.09.008


a Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO, USA
b Department of Radiology, Washington University School of Medicine, St Louis, MO, USA
c VISN 17 Center for Excellence for Research on Returning War Veterans, Waco, TX, USA
d Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA
e Baylor University, Department of Psychology and Neuroscience, Waco, TX, USA
f Department of Psychology, University of Colorado Denver, Denver, CO, USA
g Department of Neurological Surgery, University of Washington, Seattle Children's Hospital, Seattle, WA, USA


Abstract
Neuroimaging investigations of human memory encoding and retrieval have revealed that multiple regions of parietal cortex contribute to memory. Recently, a sparse network of regions within parietal cortex has been identified using resting state functional connectivity (MRI techniques). The regions within this network exhibit consistent task-related responses during memory formation and retrieval, leading to its being called the parietal memory network (PMN). Among its signature patterns are: deactivation during initial experience with an item (e.g., encoding); activation during subsequent repetitions (e.g., at retrieval); greater activation for successfully retrieved familiar words than novel words (e.g., hits relative to correctly-rejected lures). The question of interest here is whether novel words that are subjectively experienced as having been recently studied would elicit PMN activation similar to that of hits. That is, we compared old items correctly recognized to two types of novel items on a recognition test: those correctly identified as new and those incorrectly labeled as old due to their strong associative relation to the studied words (in the DRM false memory protocol). Subjective oldness plays a strong role in driving activation, as hits and false alarms activated similarly (and greater than correctly-rejected lures). © 2016 Elsevier Ltd.


Author Keywords
DRM;  False alarm;  False memory;  FMRI;  Retrieval success


Document Type: Article in Press
Source: Scopus




21) 

Kanekura, K.a d , Yagi, T.a , Cammack, A.J.c , Mahadevan, J.a , Kuroda, M.d , Harms, M.B.e , Miller, T.M.c , Urano, F.a b
Poly-dipeptides encoded by the C9ORF72 repeats block global protein translation
(2016) Human Molecular Genetics, 25 (9), art. no. ddw052, pp. 1803-1813. 

DOI: 10.1093/hmg/ddw052


a Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, MO, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States
c Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
d Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan
e Department of Neurology, Columbia University College of Physicians and Surgeon, New York, NY, United States


Abstract
The expansion of the GGGGCC hexanucleotide repeat in the non-coding region of the Chromosome 9 open-reading frame 72 (C9orf72) gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This genetic alteration leads to the accumulation of five types of poly-dipeptides translated from the GGGGCC hexanucleotide repeat. Among these, poly-proline-arginine (poly-PR) and poly-glycine-arginine (poly-GR) peptides are known to be neurotoxic. However, the mechanisms of neurotoxicity associated with these poly-dipeptides are not clear. A proteomics approach identified a number of interacting proteins with poly-PR peptide, including mRNA-binding proteins, ribosomal proteins, translation initiation factors and translation elongation factors. Immunostaining of brain sections from patients with C9orf72 ALS showed that poly-GR was colocalized with a mRNA-binding protein, hnRNPA1. In vitro translation assays showed that poly-PR and poly-GR peptides made insoluble complexes with mRNA, restrained the access of translation factors to mRNA, and blocked protein translation. Our results demonstrate that impaired protein translation mediated by poly-PR and poly-GR peptides plays a role in neurotoxicity and reveal that the pathways altered by the poly-dipeptides-mRNA complexes are potential therapeutic targets for treatment of C9orf72 FTD/ALS. © The Author 2016. Published by Oxford University Press. All rights reserved.


Document Type: Article
Source: Scopus




22) 

Toonen, J.A.a , Anastasaki, C.a , Smithson, L.J.a , Gianino, S.M.a , Li, K.b , Kesterson, R.A.b , Gutmann, D.H.a
NF1 germline mutation differentially dictates optic glioma formation and growth in neurofibromatosis-1
(2016) Human Molecular Genetics, 25 (9), art. no. ddw039, pp. 1703-1713. 

DOI: 10.1093/hmg/ddw039


a Department of Neurology, Washington University School of Medicine, PO Box 8111, 660 S. Euclid Avenue, St. Louis, MO, United States
b Department of Genetics, University of Alabama, Birmingham, AL, United States


Abstract
Neurofibromatosis type 1 (NF1) is a common neurogenetic condition characterized by significant clinical heterogeneity. A major barrier to developing precision medicine approaches for NF1 is an incomplete understanding of the factors that underlie its inherent variability. To determine the impact of the germline NF1 gene mutation on the optic gliomas frequently encountered in children with NF1, we developed genetically engineered mice harboring two representative NF1-patient-derived Nf1 gene mutations (c.2542G&gt;C;p.G848R and c.2041C&gt;T;p.R681X). We found that each germline Nf1 gene mutation resulted in different levels of neurofibromin expression. Importantly, only R681XCKO but not G848RCKO, mice develop optic gliomas with increased optic nerve volumes, glial fibrillary acid protein immunoreactivity, proliferation and retinal ganglion cell death, similar to Nf1 conditional knockout mice harboring a neomycin insertion (neo) as the germline Nf1 gene mutation. These differences in optic glioma phenotypes reflect both cell-autonomous and stromal effects of the germline Nf1 gene mutation. In this regard, primary astrocytes harboring the R681X germline Nf1 gene mutation exhibit increased basal astrocyte proliferation (BrdU incorporation) indistinguishable from neoCKO astrocytes, whereas astrocytes with the G848R mutation have lower levels of proliferation. Evidence for paracrine effects from the tumor microenvironment were revealed when R681XCKO mice were compared with conventional neoCKO mice. Relative to neoCKO mice, the optic gliomas from R681XCKO mice had more microglia infiltration and JNKThr183/Tyr185 activation, microglia-produced Ccl5, and glial AKTThr308 activation. Collectively, these studies establish that the germline Nf1 gene mutation is a major determinant of optic glioma development and growth through by both tumor cell-intrinsic and stromal effects. © The Author 2016. Published by Oxford University Press. All rights reserved.


Document Type: Article
Source: Scopus




23) 

Reddy, C.A.a b , Patel, A.a c , Gyawali, C.P.a
Impact of symptom burden and health-related quality of life (HRQOL) on esophageal motor diagnoses
(2016) Neurogastroenterology and Motility, . Article in Press. 

DOI: 10.1111/nmo.12970


a Division of Gastroenterology Washington University School of Medicine St. Louis, MO USA
b Division of Gastroenterology University of Michigan Ann Arbor, MI USA
c Division of Gastroenterology Duke University School of Medicine and Durham VA Medical Center Durham, NC USA


Abstract
Background: High-resolution manometry (HRM) categorizes esophageal motor processes into specific Chicago Classification (CC) diagnoses, but the clinical impact of these motor diagnoses on symptom burden remain unclear. Methods: Two hundred and eleven subjects (56.8±1.0 years, 66.8% F) completed symptom questionnaires (GERDQ, Mayo dysphagia questionnaire [MDQ], visceral sensitivity index, short-form 36, dominant symptom index, and global symptom severity [GSS] on a 100-mm visual analog scale) prior to HRM. Subjects were stratified according to CC v3.0 and by dominant presenting symptom; contraction wave abnormalities (CWA) were evaluated within "normal" CC. Symptom burden, impact of diagnoses, and HRQOL were compared within and between cohorts. Key Results: Major motor disorders had highest global symptom burden (P=.02), "normal" had lowest (P<.01). Dysphagia (MDQ) was highest with esophageal outflow obstruction (P=.02), but reflux symptoms (GERDQ) were similar in CC cohorts (P=ns). Absent contractility aligned best with minor motor disorders. Consequently, pathophysiologic categorization into outflow obstruction, hypermotility, and hypomotility resulted in a gradient of decreasing dysphagia and increasing reflux burden (P<.05 across groups); GSS (P=.05) was highest with hypomotility and lowest with "normal" (P=.002). Within the "normal" cohort, 33.3% had CWA; this subgroup had symptom burden similar to hypermotility. Upon stratification by symptoms, symptom burden (GSS, MDQ, HRQOL) was most profound with dysphagia. Conclusions and Inferences: Chicago Classification v3.0 diagnoses identify subjects with highest symptom burden, but pathophysiologic categorization may allow better stratification by symptom type and burden. Contraction wave abnormalities are clinically relevant and different from true normal motor function. Transit symptoms have highest yield for a motor diagnosis. © 2016 John Wiley & Sons Ltd.


Author Keywords
Chicago Classification;  Dysphagia;  High-resolution manometry;  Symptom burden


Document Type: Article in Press
Source: Scopus




24) 

Chen, Y.a , Dhar, R.a , Heitsch, L.b , Ford, A.a , Fernandez-Cadenas, I.c d , Carrera, C.d , Montaner, J.d , Lin, W.e f , Shen, D.e f g , An, H.h , Lee, J.-M.a h i
Automated quantification of cerebral edema following hemispheric infarction: Application of a machine-learning algorithm to evaluate CSF shifts on serial head CTs
(2016) NeuroImage: Clinical, 12, pp. 673-680. 

DOI: 10.1016/j.nicl.2016.09.018


a Department of Neurology, Washington University, St. Louis, MO, United States
b Emergency Medicine, Washington University, St. Louis, MO, United States
c Stroke Pharmacogenomics and Genetics, Fundacio Docencia i Recerca MutuaTerrassa, Mutua de Terrassa Hospital, Terrassa, Barcelona, Spain
d Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Universitat Autonoma de Barcelona, Barcelona, Spain
e Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, United States
f Dept. of Radiology, University of North Carolina, Chapel Hill, NC, United States
g Department of Brain and Cognitive Engineering, Korea University, Seoul, South Korea
h Radiology, Washington University, St. Louis, MO, United States
i Biomedical Engineering, Washington University, St. Louis, MO, United States


Abstract
Although cerebral edema is a major cause of death and deterioration following hemispheric stroke, there remains no validated biomarker that captures the full spectrum of this critical complication. We recently demonstrated that reduction in intracranial cerebrospinal fluid (CSF) volume (? CSF) on serial computed tomography (CT) scans provides an accurate measure of cerebral edema severity, which may aid in early triaging of stroke patients for craniectomy. However, application of such a volumetric approach would be too cumbersome to perform manually on serial scans in a real-world setting. We developed and validated an automated technique for CSF segmentation via integration of random forest (RF) based machine learning with geodesic active contour (GAC) segmentation. The proposed RF + GAC approach was compared to conventional Hounsfield Unit (HU) thresholding and RF segmentation methods using Dice similarity coefficient (DSC) and the correlation of volumetric measurements, with manual delineation serving as the ground truth. CSF spaces were outlined on scans performed at baseline (&lt; 6 h after stroke onset) and early follow-up (FU) (closest to 24 h) in 38 acute ischemic stroke patients. RF performed significantly better than optimized HU thresholding (p &lt; 10− 4 in baseline and p &lt; 10− 5 in FU) and RF + GAC performed significantly better than RF (p &lt; 10− 3 in baseline and p &lt; 10− 5 in FU). Pearson correlation coefficients between the automatically detected ? CSF and the ground truth were r = 0.178 (p = 0.285), r = 0.876 (p &lt; 10− 6) and r = 0.879 (p &lt; 10− 6) for thresholding, RF and RF + GAC, respectively, with a slope closer to the line of identity in RF + GAC. When we applied the algorithm trained from images of one stroke center to segment CTs from another center, similar findings held. In conclusion, we have developed and validated an accurate automated approach to segment CSF and calculate its shifts on serial CT scans. This algorithm will allow us to efficiently and accurately measure the evolution of cerebral edema in future studies including large multi-site patient populations. © 2016 The Authors


Author Keywords
Active contour;  Cerebral edema;  CSF segmentation;  Ischemic stroke CT;  Mass effect;  Random forest


Document Type: Article
Source: Scopus




 

25) 

Salt, A.N.a c d , Plontkey, S.K.b e
Drug Diffusion to the Apex of the Human Cochlea? A Comment on "kang WS, Nguyen K, McKenna CE, Sewell WF, McKenna MJ, Jung DH. Intracochlear Drug Delivery Through the Oval Window in Fresh Cadaveric Human Temporal Bones"
(2016) Otology and Neurotology, 37 (9), pp. 1462-1463. 

DOI: 10.1097/MAO.0000000000001146


a Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Otorhinolaryngology, Head and Neck Surgery, Martin Luther University Halle-Wittenberg Halle (Saale), Germany
c Scientific Advisory Board of Otonomy, Inc., San Diego, United States
d Consultant for Otonomy, Inc., United States
e Scientific Advisory Board of AudioCure Pharma GmbH, Berlin, Germany


Document Type: Letter
Source: Scopus

 

October 20, 2016

1) 

Mikulka, C.R.a b , Sands, M.S.a b
Treatment for Krabbe's disease: Finding the combination
(2016) Journal of Neuroscience Research, 94 (11), pp. 1126-1137. 

DOI: 10.1002/jnr.23822


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


Abstract
Globoid cell leukodystrophy (GLD) is an autosomal recessive neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactocerebrosidase (GALC). GALC is responsible for catabolism of certain glycolipids, including the toxic compound galactosylsphingosine (psychosine). Histological signs of disease include the widespread loss of myelin in the central and peripheral nervous systems, profound neruroinflammation, and axonal degeneration. Patients suffering from GLD also display neurological deterioration. Many different individual therapies have been investigated in the murine model of the GLD, the Twitcher mouse, with minimal success. The current standard of care for GLD patients, hematopoietic stem cell transplantation, serves only to delay disease progression and is not an effective cure. However, combination therapies that target different pathogenic mechanisms/pathways have been more effective at reducing histological signs of disease, delaying disease onset, prolonging life span, and improving behavioral/cognitive functions in rodent models of Krabbe's disease. In some cases, dramatic synergy between the various therapies has been observed. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.


Author Keywords
bone marrow transplant;  galactocerebrosidase;  gene therapy;  Krabbe's disease;  lysosomal storage disease


Document Type: Review
Source: Scopus




2) 

Hosseini, S.M.H.a , Mazaika, P.a , Mauras, N.b , Buckingham, B.c , Weinzimer, S.A.d , Tsalikian, E.e , White, N.H.f , Reiss, A.L.a , for the Diabetes Research in Children Network (DirecNet)g
Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes
(2016) Human Brain Mapping, 37 (11), pp. 4034-4046. 

DOI: 10.1002/hbm.23293


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


Abstract
Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early-onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large-scale brain networks. In the present study, we applied graph-theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization—an architecture that is simultaneously highly segregated and integrated—the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early-onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034–4046, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.


Author Keywords
brain networks;  diabetes;  graph theoretical analysis;  gray matter volume;  network efficiency;  network resilience


Document Type: Article
Source: Scopus




3) 

Severtson, S.G.a , Ellis, M.S.b , Kurtz, S.P.c , Rosenblum, A.d , Cicero, T.J.b , Parrino, M.W.d , Gilbert, M.K.e , Buttram, M.E.c , Dasgupta, N.e , BucherBartelson, B.a , Green, J.L.a , Dart, R.C.a
Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone
(2016) Drug and Alcohol Dependence, 168, pp. 219-229. 

DOI: 10.1016/j.drugalcdep.2016.09.018


a Rocky Mountain Poison and Drug Center, 777 Bannock Street, Mailcode 0180, Denver, CO, United States
b Department of Psychiatry, Washington University School of Medicine, Washington University School of Medicine, Box 8134, 660 S Euclid, St. Louis, MO, United States
c Center for Applied Research on Substance Use and Health Disparities, Department of Justice and Human Services, College of Humanities, Arts and Social Sciences, Nova Southeastern University, 7255 NE 4th Avenue, Suite 112, Miami, FL, United States
d American Association for the Treatment of Opioid Dependence, New York, NY, United States
e Epidemico, Inc., 50 Milk St., 20th floor, Boston, MA, United States


Abstract
Background The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin®) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. Methods Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS®) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. Results OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Discussion Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years. © 2016


Author Keywords
Abuse;  Diversion;  Drug abuse;  Opioid analgesics;  OxyContin


Document Type: Article
Source: Scopus




4) 

Hu, P.a , Li, Y.b , Nikolaishvili-Feinberg, N.c , Scesa, G.d , Bi, Y.a , Pan, D.e f , Moore, D.g , Bongarzone, E.R.d , Sands, M.S.b , Miller, R.c h , Kafri, T.a
Hematopoietic Stem cell transplantation and lentiviral vector-based gene therapy for Krabbe's disease: Present convictions and future prospects
(2016) Journal of Neuroscience Research, 94 (11), pp. 1152-1168. 

DOI: 10.1002/jnr.23847


a Gene Therapy Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
b Department of Internal Medicine, Washington University in St. Louis, School of Medicine, St Louis, MO, United States
c Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
d Department of Anatomy and Cell Biology, College of Medicine, University of Illinois Chicago, Chicago, IL, United States
e Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
f Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States
g Biostatistics Core Facility, UNC Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
h Departments of Pathology and Laboratory Medicine and of Neurology, Neurosciences Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States


Abstract
Currently, presymtomatic hematopoietic stem and progenitor cell transplantation (HSPCT) is the only therapeutic modality that alleviates Krabbe's disease (KD)-induced central nervous system damage. However, all HSPCT-treated patients exhibit severe deterioration in peripheral nervous system function characterized by major motor and expressive language pathologies. We hypothesize that a combination of several mechanisms contribute to this phenomenon, including 1) nonoptimal conditioning protocols with consequent inefficient engraftment and biodistribution of donor-derived cells and 2) insufficient uptake of donor cell-secreted galactocerebrosidease (GALC) secondary to a naturally low expression level of the cation-independent mannose 6-phosphate-receptor (CI-MPR). We have characterized the effects of a busulfan (Bu) based conditioning regimen on the efficacy of HSPCT in prolonging twi mouse average life span. There was no correlation between the efficiency of bone marrow engraftment of donor cells and twi mouse average life span. HSPCT prolonged the average life span of twi mice, which directly correlated with the aggressiveness of the Bu-mediated conditioning protocols. HSPC transduced with lentiviral vectors carrying the GALC cDNA under control of cell-specific promoters were efficiently engrafted in twi mouse bone marrow. To facilitate HSPCT-mediated correction of GALC deficiency in target cells expressing low levels of CI-MPR, a novel GALC fusion protein including the ApoE1 receptor was developed. Efficient cellular uptake of the novel fusion protein was mediated by a mannose-6-phosphate-independent mechanism. The novel findings described here elucidate some of the cellular mechanisms that impede the cure of KD patients by HSPCT and concomitantly open new directions to enhance the therapeutic efficacy of HSPCT protocols for KD. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.


Author Keywords
AB_10563203;  AB_10611731;  AB_10894189;  AB_2034021;  AB_313497;  AB_398535;  busulfan conditioning;  erythroid-specific promoter;  Galc-AErbd (ApoE receptor binding domain);  IMSR_JAX:000845;  IMSR_JAX:002014;  myeloid-specific promoter


Document Type: Article
Source: Scopus




5) 

Germann, A.L.a , Shin, D.J.a , Manion, B.D.a , Edge, C.J.b c , Smith, E.H.b , Franks, N.P.b , Evers, A.S.a d , Akk, G.a d
Activation and modulation of recombinant glycine and GABAA receptors by 4-halogenated analogues of propofol
(2016) British Journal of Pharmacology, pp. 3110-3120. 

DOI: 10.1111/bph.13566


a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Life Sciences, Imperial College London, South Kensington, United Kingdom
c Department of Anaesthetics, Royal Berkshire NHS Foundation Trust, Reading, United Kingdom
d Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Background and Purpose: Glycine receptors are important players in pain perception and movement disorders and therefore important therapeutic targets. Glycine receptors can be modulated by the intravenous anaesthetic propofol (2,6-diisopropylphenol). However, the drug is more potent, by at least one order of magnitude, on GABAA receptors. It has been proposed that halogenation of the propofol molecule generates compounds with selective enhancement of glycinergic modulatory properties. Experimental Approach: We synthesized 4-bromopropofol, 4-chloropropofol and 4-fluoropropofol. The direct activating and modulatory effects of these drugs and propofol were compared on recombinant rat glycine and human GABAA receptors expressed in oocytes. Behavioural effects of the compounds were compared in the tadpole loss-of-righting assay. Key Results: Concentration–response curves for potentiation of homomeric α1, α2 and α3 glycine receptors were shifted to lower drug concentrations, by 2–10-fold, for the halogenated compounds. Direct activation by all compounds was minimal with all subtypes of the glycine receptor. The four compounds were essentially equally potent modulators of the α1β3γ2L GABAA receptor with EC50 between 4 and 7 μM. The EC50 for loss-of-righting in Xenopus tadpoles, a proxy for loss of consciousness and considered to be mediated by actions on GABAA receptors, ranged from 0.35 to 0.87 μM. Conclusions and Implications: We confirm that halogenation of propofol more strongly affects modulation of homomeric glycine receptors than α1β3γ2L GABAA receptors. However, the effective concentrations of all tested halogenated compounds remained lower for GABAA receptors. We infer that 4-bromopropofol, 4-chloropropofol and 4-fluoropropofol are not selective homomeric glycine receptor modulators. © 2016 The British Pharmacological Society


Document Type: Article
Source: Scopus




6) 

Bradbury, A.M.a , Bagel, J.H.a , Jiang, X.b , Swain, G.P.a , Prociuk, M.L.a , Fitzgerald, C.A.a , O'Donnell, P.A.a , Braund, K.G.c , Ory, D.S.b , Vite, C.H.a
Clinical, electrophysiological, and biochemical markers of peripheral and central nervous system disease in canine globoid cell leukodystrophy (Krabbe's disease)
(2016) Journal of Neuroscience Research, 94 (11), pp. 1007-1017. 

DOI: 10.1002/jnr.23838


a Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States
b Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
c Veterinary Neurological Consulting Services, Dadeville, AL, United States


Abstract
Globoid cell leukodystrophy (GLD), or Krabbe's disease, is a debilitating and always fatal pediatric neurodegenerative disease caused by a mutation in the gene encoding the hydrolytic enzyme galactosylceramidase (GALC). In the absence of GALC, progressive loss of myelin and accumulation of a neurotoxic substrate lead to incapacitating loss of motor and cognitive function and death, typically by 2 years of age. Currently, there is no cure. Recent convincing evidence of the therapeutic potential of combining gene and cell therapies in the murine model of GLD has accelerated the requirement for validated markers of disease to evaluate therapeutic efficacy. Here we demonstrate clinically relevant and quantifiable measures of central (CNS) and peripheral (PNS) nervous system disease progression in the naturally occurring canine model of GLD. As measured by brainstem auditory-evoked response testing, GLD dogs demonstrated a significant increase in I-V interpeak latency and hearing threshold at all time points. Motor nerve conduction velocities (NCVs) in GLD dogs were significantly lower than normal by 12–16 weeks of age, and sensory NCV was significantly lower than normal by 8–12 weeks of age, serving as a sensitive indicator of peripheral nerve dysfunction. Post-mortem histological evaluations confirmed neuroimaging and electrodiagnostic assessments and detailed loss of myelin and accumulation of storage product in the CNS and the PNS. Additionally, cerebrospinal fluid psychosine concentrations were significantly elevated in GLD dogs, demonstrating potential as a biochemical marker of disease. These data demonstrate that CNS and PNS disease progression can be quantified over time in the canine model of GLD with tools identical to those used to assess human patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.


Author Keywords
biomarker;  CSF psychosine;  electrophysiological testing;  Krabbe's disease;  large animal model;  neuroimaging


Document Type: Article
Source: Scopus




7) 

Agrawal, A.a , Few, L.a , Nelson, E.C.a , Deutsch, A.b , Grant, J.D.a , Bucholz, K.K.a , Madden, P.A.F.a , Heath, A.C.a , Lynskey, M.T.c
Adolescent cannabis use and repeated voluntary unprotected sex in women
(2016) Addiction, 111 (11), pp. 2012-2020. 

DOI: 10.1111/add.13490


a Washington University School of Medicine, Department of Psychiatry, Saint Louis, MO, United States
b University of Missouri-Columbia, Department of Psychological Sciences, Columbia, MO, United States
c King's College, Institute of Psychiatry, Psychology and Neuroscience, Addictions Department, London, United Kingdom


Abstract
Background and aims: Substance use has been implicated in the onset and maintenance of risky sexual behaviors, which have particularly devastating consequences in young women. This study examined whether (i) adolescent onset of cannabis use is associated with repeated voluntary unprotected sex in women and (ii) whether this association persists after accounting for correlated familial influences. Design: General population sample of female twins. Setting: Midwestern United States. Participants: A total of 2784 sexually active twin women (15.5% African American) aged 18–27 years (assessed 2002–05), including 119 dizygotic (DZ) and 115 monozygotic (MZ) discordant pairs. Measurements: Self-report interview data on cannabis use that first occurred prior to age 17 (27.1%) and repeated voluntary unprotected sex (27.2%). Key covariates included early onset of regular drinking, regular smoking, sexual debut and menstruation as well as conduct disorder symptoms and childhood sexual abuse. Findings: Compared with never users and those who started using cannabis at a later age, adolescent cannabis users were more likely to report repeated voluntary unprotected sex [odds ratio (OR) = 2.69; 95% confidence interval (CI) = 2.24–3.22]. Genetic (rg = 0.57, 95% CI = 0.38–0.87) and non-shared environmental (re = 0.21, 95% CI = 0.02–0.38) factors contributed to the association. After accounting for correlated familial factors, there was a consistent elevation in the likelihood of repeated voluntary unprotected sex in the exposed twin relative to her genetically identical never/late-onset user co-twin (unadjusted OR = 2.25, 95% CI = 1.14–4.44), even after adjustment for covariates (adjusted OR = 2.27, 95% CI = 1.08–4.80). Conclusions: Women who start using cannabis during adolescence appear to be more likely to report voluntary engagement in repeated unprotected sex than women who never use cannabis or who initiate cannabis use after adolescence. The results appear to be independent of shared genetic influences. © 2016 Society for the Study of Addiction


Author Keywords
Cannabis;  discordant;  risky;  sexual;  twin;  unprotected


Document Type: Article
Source: Scopus




8) 

Waldum, E.R., Dufault, C.L., McDaniel, M.A.
Prospective Memory Training: Outlining a New Approach
(2016) Journal of Applied Gerontology, 35 (11), pp. 1211-1234. Cited 1 time.

DOI: 10.1177/0733464814559418


Department of Psychology, Washington University in St. Louis, Campus Box 1125, One Brookings Dr., St. Louis, MO, United States


Abstract
Prospective memory (PM) tasks are those that must be performed in the future (e.g., attend an appointment). While these everyday tasks can be especially relevant for older adults (i.e., medication adherence), and have been associated with age-related decline, PM has been virtually overlooked in the cognitive training domain. This article describes the first comprehensive PM training intervention. Older adults (age 55 to 75) who received training completed 8 weekly PM training sessions that consisted of variable PM training tasks, strategy-focused discussion, and homework assignments. Those assigned to a control group completed only the first and last training task. On both a real-world proxy PM transfer task and the training tasks detailed here, there was a positive impact of PM training, suggesting practical benefits of the current training package for older adults. Benefits may also extend to other special populations who experience PM impairments (e.g., traumatic brain injury [TBI], Parkinson's). © Southern Gerontological Society.


Author Keywords
aging;  event-based;  intervention;  prospective memory;  time-based


Document Type: Article
Source: Scopus




9) 

Oni, E.N.a , Halikere, A.b , Li, G.b , Toro-Ramos, A.J.a , Swerdel, M.R.a , Verpeut, J.L.c , Moore, J.C.d e , Bello, N.T.c , Bierut, L.J.f , Goate, A.g , Tischfield, J.A.d e , Pang, Z.P.b d , Hart, R.P.a d
Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele
(2016) Scientific Reports, 6, art. no. 34341, . 

DOI: 10.1038/srep34341


a Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, United States
b Child Health Institute of New Jersey, Dept. of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
c Department of Animal Sciences, Rutgers University, New Brunswick, NJ, United States
d Human Genetics Institute of New Jersey, Rutgers University, RWJMS, Piscataway, NJ, United States
e Department of Human Genetics, Rutgers University, Piscataway, NJ, United States
f Department of Psychiatry, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
g Neuroscience Department, Icahn School of Medicine at Mount Sinai, New York, NY, United States


Abstract
Genetic variation in nicotinic receptor alpha 5 (CHRNA5) has been associated with increased risk of addiction-associated phenotypes in humans yet little is known the underlying neural basis. Induced pluripotent stem cells (iPSCs) were derived from donors homozygous for either the major (D398) or the minor (N398) allele of the nonsynonymous single nucleotide polymorphism (SNP), rs16969968, in CHRNA5. To understand the impact of these nicotinic receptor variants in humans, we differentiated these iPSCs to dopamine (DA) or glutamatergic neurons and then tested their functional properties and response to nicotine. Results show that N398 variant human DA neurons differentially express genes associated with ligand receptor interaction and synaptic function. While both variants exhibited physiological properties consistent with mature neuronal function, the N398 neuronal population responded more actively with an increased excitatory postsynaptic current response upon the application of nicotine in both DA and glutamatergic neurons. Glutamatergic N398 neurons responded to lower nicotine doses (0.1 μM) with greater frequency and amplitude but they also exhibited rapid desensitization, consistent with previous analyses of N398-associated nicotinic receptor function. This study offers a proof-of-principle for utilizing human neurons to study gene variants contribution to addiction.


Document Type: Article
Source: Scopus




10) 

Sassi, C.a b c d , Nalls, M.A.b , Ridge, P.G.e , Gibbs, J.R.b , Ding, J.b , Lupton, M.K.f g , Troakes, C.f , Lunnon, K.f h , Al-Sarraj, S.f , Brown, K.S.i , Medway, C.i , Clement, N.i , Lord, J.i , Turton, J.i , Bras, J.a , Almeida, M.R.j , Passmore, P.t , Craig, D.u , Johnston, J.v , McGuinness, B.w , Todd, S.x , Heun, R.y , Kölsch, H.z , Kehoe, P.G.aa , Vardy, E.R.L.C.ab , Hooper, N.M.ac , Mann, D.M.ad , Pickering-Brown, S.ae , Brown, K.af , Lowe, J.ag , Morgan, K.ah , Smith, A.D.ai , Wilcock, G.aj , Warden, D.ak , Holmes, C.al , Holstege, H.k , Louwersheimer, E.k , van der Flier, W.M.k , Scheltens, P.k , Van Swieten, J.C.k l , Santana, I.m n , Oliveira, C.o p , Morgan, K.i , Powell, J.F.f , Kauwe, J.S.e q , Cruchaga, C.r , Goate, A.M.s , Singleton, A.B.b , Guerreiro, R.a , Hardy, J.a
ABCA7 p.G215S as potential protective factor for Alzheimer's disease
(2016) Neurobiology of Aging, 46, pp. 235.e1-235.e9. 

DOI: 10.1016/j.neurobiolaging.2016.04.004


a Reta Lila, Weston Research Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
b Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
c Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Charite’ Universitätmedizin, Berlin, Germany
d German Center for Neurodegenerative Diseases (DZNE), Berlin site, Germany
e Department of Biology, Brigham Young University, Provo, UT, United States
f King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom
g QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
h Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, United Kingdom
i Translation Cell Sciences-Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom
j Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
k Department of Neurology, Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, Netherlands
l Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands
m Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
n Faculty of Medicine, Coimbra University, Coimbra, Portugal
o CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
p Laboratory of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
q Department of Neuroscience, Brigham Young University, Provo, UT, United States
r Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO, United States
s Icahn School of Medicine at Mount Sinai, Icahn Medical Institute, New York, NY, United States


Abstract
Genome-wide association studies (GWASs) have been effective approaches to dissect common genetic variability underlying complex diseases in a systematic and unbiased way. Recently, GWASs have led to the discovery of over 20 susceptibility loci for Alzheimer's disease (AD). Despite the evidence showing the contribution of these loci to AD pathogenesis, their genetic architecture has not been extensively investigated, leaving the possibility that low frequency and rare coding variants may also occur and contribute to the risk of disease. We have used exome and genome sequencing data to analyze the single independent and joint effect of rare and low-frequency protein coding variants in 9 AD GWAS loci with the strongest effect sizes after APOE (BIN1, CLU, CR1, PICALM, MS4A6A, ABCA7, EPHA1, CD33, and CD2AP) in a cohort of 332 sporadic AD cases and 676 elderly controls of British and North-American ancestry. We identified coding variability in ABCA7 as contributing to AD risk. This locus harbors a low-frequency coding variant (p.G215S, rs72973581, minor allele frequency = 4.3%) conferring a modest but statistically significant protection against AD (p-value = 0.024, odds ratio = 0.57, 95% confidence interval = 0.41–0.80). Notably, our results are not driven by an enrichment of loss of function variants in ABCA7, recently reported as main pathogenic factor underlying AD risk at this locus. In summary, our study confirms the role of ABCA7 in AD and provides new insights that should address functional studies. © 2016 The Authors


Author Keywords
ABCA7;  Alzheimer's disease (AD);  Genome-wide association studies (GWASs);  Protective variant;  Whole exome sequencing (WES);  Whole genome sequencing (WGS)


Document Type: Article
Source: Scopus




11) 

Naismith, R.T.
Multiple sclerosis should be treated using a step-down strategy rather than a step-up strategy-NO
(2016) Multiple Sclerosis, 22 (11), pp. 1400-1402. Cited 1 time.

DOI: 10.1177/1352458516644676


Neurology, Washington University in St. Louis, Campus Box 8111, 660 South Euclid Ave., St. Louis, MO, United States


Document Type: Article
Source: Scopus




12) 

Kocdor, P.a , Iseli, C.E.b , Teagle, H.F.a , Woodard, J.a , Park, L.a , Zdanski, C.J.a , Brown, K.D.a , Adunka, O.F.c , Buchman, C.A.d
The effect of interdevice interval on speech perception performance among bilateral, pediatric cochlear implant recipients
(2016) Laryngoscope, 126 (10), pp. 2389-2394. 

DOI: 10.1002/lary.26012


a Department of Otolaryngology Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
b Department of Otolaryngology Head and Neck Surgery, The Royal Victorian Eye and Ear Hospital, Melbourne, Australia
c Department of Otolaryngology Head and Neck Surgery, The Ohio State University, Columbus, OH, United States
d Department of Otolaryngology, Washington University in St. Louis, St Louis, MO, United States


Abstract
Objectives/Hypothesis: To determine if prolongation of the interdevice interval in children receiving bilateral cochlear implants adversely affects speech perception outcomes. Study Design: Retrospective chart review. Methods: Retrospective review of our pediatric cochlear implant database was performed. Children who had undergone revision surgery or had less than 12 months listening experience with either the first or second implant were excluded. The interdevice interval, best Phonetically Balanced Kindergarten word lists (PBK) score from each ear, and demographic data about each patient were collected. A ratio of PBK was generated (PBK second side/PBK first side) to minimize potential confounding from other individual patient factors that affect speech outcomes. Results: Two hundred forty children met the study criteria. Mean age at first cochlear implantation (CI) was 3.2 years (0.6–17.9), and the second was 6.6 years (0.8–22.4). Mean best PBK score from the first CI side was 83.8% (0–100), and the second was 67.5% (0–100) (P &lt;.001). When the PBK ratio was plotted against interdevice interval, R2 was 0.47 (P &lt;.001). When analyzed for hearing stability, those with a progressive loss history demonstrated less influence of prolonged interdevice interval on performance. Multivariate analysis did not identify other factors influencing the ratio. A line of best fit for those with stable hearing loss suggested best outcomes were with an interdevice interval less than 3 to 4 years. Beyond 7 to 8 years, very few achieved useful speech recognition from the second CI. Conclusions: Where possible, the second implant should be received within 3 to 4 years of the first to maximize outcome in those with stable, severe to profound sensorineural hearing loss. Level of Evidence: 4. Laryngoscope, 126:2389–2394, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.


Author Keywords
bilateral;  Cochlear implant;  interdevice interval;  speech perception outcomes


Document Type: Article
Source: Scopus




13) 

Lin, J.B.a b , Kubota, S.a , Ban, N.a , Yoshida, M.b c , Santeford, A.a , Sene, A.a , Nakamura, R.a , Zapata, N.a , Kubota, M.a , Tsubota, K.e , Yoshino, J.d , Imai, S.-I.c , Apte, R.S.a c d
NAMPT-Mediated NAD+ Biosynthesis Is Essential for Vision In Mice
(2016) Cell Reports, 17 (1), pp. 69-85. 

DOI: 10.1016/j.celrep.2016.08.073


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Neuroscience Graduate Program, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
c Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan


Abstract
Photoreceptor death is the endpoint of many blinding diseases. Identifying unifying pathogenic mechanisms in these diseases may offer global approaches for facilitating photoreceptor survival. We found that rod or cone photoreceptor-specific deletion of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the major NAD+ biosynthetic pathway beginning with nicotinamide, caused retinal degeneration. In both cases, we could rescue vision with nicotinamide mononucleotide (NMN). Significantly, retinal NAD+ deficiency was an early feature of multiple mouse models of retinal dysfunction, including light-induced degeneration, streptozotocin-induced diabetic retinopathy, and age-associated dysfunction. Mechanistically, NAD+ deficiency caused metabolic dysfunction and consequent photoreceptor death. We further demonstrate that the NAD+-dependent mitochondrial deacylases SIRT3 and SIRT5 play important roles in retinal homeostasis and that NAD+ deficiency causes SIRT3 dysfunction. These findings demonstrate that NAD+ biosynthesis is essential for vision, provide a foundation for future work to further clarify the mechanisms involved, and identify a unifying therapeutic target for diverse blinding diseases. © 2016 The Author(s)


Author Keywords
metabolism;  mitochondria;  NAD+;  neurodegeneration;  photoreceptor;  retina;  sirtuins


Document Type: Article
Source: Scopus




14) 

Rouse, A.G., Williams, J.J., Wheeler, J.J., Moran, D.W.
Spatial co-adaptation of cortical control columns in a micro-ECoG brain-computer interface
(2016) Journal of Neural Engineering, 13 (5), art. no. 056018, . 

DOI: 10.1088/1741-2560/13/5/056018


Department of Biomedical Engineering, Washington University, One Brookings Drive, Saint Louis, MO, United States


Abstract
Objective. Electrocorticography (ECoG) has been used for a range of applications including electrophysiological mapping, epilepsy monitoring, and more recently as a recording modality for brain-computer interfaces (BCIs). Studies that examine ECoG electrodes designed and implanted chronically solely for BCI applications remain limited. The present study explored how two key factors influence chronic, closed-loop ECoG BCI: (i) the effect of inter-electrode distance on BCI performance and (ii) the differences in neural adaptation and performance when fixed versus adaptive BCI decoding weights are used. Approach. The amplitudes of epidural micro-ECoG signals between 75 and 105 Hz with 300 μm diameter electrodes were used for one-dimensional and two-dimensional BCI tasks. The effect of inter-electrode distance on BCI control was tested between 3 and 15 mm. Additionally, the performance and cortical modulation differences between constant, fixed decoding using a small subset of channels versus adaptive decoding weights using the entire array were explored. Main results. Successful BCI control was possible with two electrodes separated by 9 and 15 mm. Performance decreased and the signals became more correlated when the electrodes were only 3 mm apart. BCI performance in a 2D BCI task improved significantly when using adaptive decoding weights (80%-90%) compared to using constant, fixed weights (50%-60%). Additionally, modulation increased for channels previously unavailable for BCI control under the fixed decoding scheme upon switching to the adaptive, all-channel scheme. Significance. Our results clearly show that neural activity under a BCI recording electrode (which we define as a 'cortical control column') readily adapts to generate an appropriate control signal. These results show that the practical minimal spatial resolution of these control columns with micro-ECoG BCI is likely on the order of 3 mm. Additionally, they show that the combination and interaction between neural adaptation and machine learning are critical to optimizing ECoG BCI performance. © 2016 IOP Publishing Ltd.


Author Keywords
BCI;  ECoG;  neural adaptation


Document Type: Article
Source: Scopus




15) 

Roos, P.
The Great Listener1
(2016) Psychoanalytic Perspectives, 13 (3), pp. 294-299. 

DOI: 10.1080/1551806X.2016.1228901


Washington University, St. Louis, United States


Abstract
This article is a translation of a story published in Die Zeit, April 27, 2006. It describes the dramatic single session a young woman, Margarethe Walter (married name, Margarethe Lutz), had with Sigmund Freud in 1936, as she told it to the author Peter Roos 70 years later. Copyright © 2016 National Institute for the Psychotherapies.


Author Keywords
Adult;  dissent;  Freud


Document Type: Article
Source: Scopus




16) 

Beitscher-Campbell, H.a b c , Blum, K.c d e f g h i k m n , Febo, M.d , Madigan, M.A.i , Giordano, J.c , Badgaiyan, R.D.j , Braverman, E.R.g , Dushaj, K.g , Li, M.g , Gold, M.S.k l
Pilot clinical observations between food and drug seeking derived from fifty cases attending an eating disorder clinic
(2016) Journal of Behavioral Addictions, 5 (3), pp. 533-541. 

DOI: 10.1556/2006.5.2016.055


a A New Beginning PA, North Miami Beach, FL, United States
b Ocean Breeze Recovery Program, Pompano Beach, FL, United States
c National Institute of Holistic Addiction Studies, North Miami Beach, FL, United States
d Department of Psychiatry, McKnight Brain Institute, University of Florida, College of Medicine, Box 100183, Gainesville, FL, United States
e Division of Neuroscience-based Therapy, Summit Estate Recovery Center, Las Gatos, CA, United States
f Department of Psychiatry, University of Vermont, Burlington, VT, United States
g Department of Neurological Research, PATH Foundation NY, New York, NY, United States
h Dominion Diagnostics, LLC, North Kingstown, RI, United States
i IGENE, LLC, Austin, TX, United States
j Department of Psychiatry and Laboratory for Radiochemistry, University of Minnesota, Minneapolis, MN, United States
k Department of Psychiatry and Behavioral Sciences, Keck School of Medicine of USC, Los Angeles, CA, United States
l Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
m Division of Neuroscience Research and Addiction Therapy, Shores Treatment and Recovery, Port Saint Lucie, FL, United States
n Institute of Psychology, Eötvös Loránd University, Budapest, Hungary


Abstract
Background: The reward deficiency syndrome hypothesis posits that genes are responsible for reward dependence and related behaviors. There is evidence that both bulimia and anorexia nervosa, especially in women, have been linked to a lifetime history of substance use disorder (SUD). There are difficulties in accepting food as an addiction similar to drugs; however, increasingly neuroimaging studies favor such an assertion. Case presentations: We are reporting the evidence of comorbidity of eating disorders with SUD found within these case presentations. We show 50 case reports derived from two independent treatment centers in Florida that suggest the commonality between food and drug addictions. In an attempt to provide data from this cohort, many participants did not adequately respond to our questionnaire. Discussion: We propose that dopamine agonist therapy may be of common benefit. Failure in the past may reside in too powerful D2 agonist activity leading to D2 receptor downregulation, while the new methodology may cause a reduction of "dopamine resistance" by inducing "dopamine homeostasis." While this is not a definitive study, it does provide some additional clinical evidence that these two addictions are not mutually exclusive. Conclusion: Certainly, it is our position that there is an overlap between food and drug seeking behavior. We propose that the studies focused on an effort to produce natural activation of dopaminergic reward circuitry as a type of common therapy may certainly be reasonable. Additional research is warranted. © 2016 The Author(s).


Author Keywords
Commonality;  Dopamine pathways;  Eating disorder;  Food and drug addictions;  Reward deficiency syndrome


Document Type: Article
Source: Scopus




17) 

Cavazos-Rehg, P.A., Sowles, S.J., Krauss, M.J., Agbonavbare, V., Grucza, R., Bierut, L.
A content analysis of tweets about high-potency marijuana
(2016) Drug and Alcohol Dependence, 166, pp. 100-108. 

DOI: 10.1016/j.drugalcdep.2016.06.034


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


Abstract
Introduction “Dabbing” involves heating extremely concentrated forms of marijuana to high temperatures and inhaling the resulting vapor. We studied themes describing the consequences of using highly concentrated marijuana by examining the dabbing-related content on Twitter. Methods Tweets containing dabbing-related keywords were collected from 1/1–1/31/2015 (n = 206,854). A random sample of 5000 tweets was coded for content according to pre-determined categories about dabbing-related behaviors and effects experienced using a crowdsourcing service. An examination of tweets from the full sample about respiratory effects and passing out was then conducted by selecting tweets with relevant keywords. Results Among the 5000 randomly sampled tweets, 3540 (71%) were related to dabbing marijuana concentrates. The most common themes included mentioning current use of concentrates (n = 849; 24%), the intense high and/or extreme effects from dabbing (n = 763; 22%) and excessive/heavy dabbing (n = 517; 15%). Extreme effects included both physiological (n = 124/333; 37%) and psychological effects (n = 55/333; 17%). The most common physiologic effects, passing out (n = 46/333; 14%) and respiratory effects (n = 30/333; 9%), were then further studied in the full sample of tweets. Coughing was the most common respiratory effect mentioned (n = 807/1179; 68%), and tweeters commonly expressed dabbing with intentions to pass out (416/915; 45%). Conclusions This study adds to the limited understanding of marijuana concentrates and highlights self-reported physical and psychological effects from this type of marijuana use. Future research should further examine these effects and the potential severity of health consequences associated with concentrates. © 2016 Elsevier Ireland Ltd


Author Keywords
Cannabis;  Marijuana concentrates;  Marijuana smoking;  Social media;  Twitter


Document Type: Article
Source: Scopus




18) 

Shoykhet, M.a b , Middleton, J.W.c d
Cardiac arrest-induced global brain hypoxia-ischemia during development affects spontaneous activity organization in rat sensory and motor thalamocortical circuits during adulthood
(2016) Frontiers in Neural Circuits, 10 (AUG), art. no. 68, . 

DOI: 10.3389/fncir.2016.00068


a Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Department of Pediatrics, St. Louis Children’s Hospital, St. Louis, MO, United States
c Department of Cell Biology and Anatomy, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, United States
d Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, United States


Abstract
Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window. We examined the effect of cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats on spontaneous and evoked firing of somatosensory thalamocortical neurons and on large-scale correlations in the motor thalamocortical circuit. The mean spontaneous and sensory-evoked firing rate activity and variability were higher in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and variability were correlated in uninjured rats, but not correlated in neurons from CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm) neurons persisted into adulthood. Additionally, we found that neurons in the entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had higher variability and higher levels of burst firing after injury. Correlated levels of power in local field potentials (LFPs) between the EPN and the motor cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic-ischemic injury during development leads to abnormal spontaneous and sensory stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs likely permanently and detrimentally affect the organization of cortical circuitry and processing of sensory information. Hypoxic-ischemic injury also leads to abnormal single neuron and population level activity in the basal ganglia that may contribute to motor dysfunction after injury. Combination of deficits in sensory and motor thalamocortical circuit function may negatively impact sensorimotor integration in CA survivors. Modulation of abnormal activity patterns post-injury may represent a novel therapeutic target to improve neurologic function in survivors. © 2016 Shoykhet and Middleton.


Author Keywords
Correlation;  Developmental period;  Ischemic injury;  Sensory thresholds;  Spontaneous activity


Document Type: Article
Source: Scopus




19) 

Raghavan, R.a , Brown, D.S.b , Allaire, B.T.c , Ross, R.E.b , Landsverk, J.d
Associations between magnitude of child maltreatment and Medicaid expenditures for psychotropic medications
(2016) Psychiatric Services, 67 (8), pp. 916-919. 

DOI: 10.1176/appi.ps.201500211


a School of Social Work, Rutgers, State University of New Jersey, New Brunswick, United States
b George Warren Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
c RTI International, Research Triangle Park, NC, United States
d Child and Adolescent Services Research Center, Rady Children's Hospital, San Diego, United States


Abstract
Objective: This study examined relationships between various measures of the severity of child maltreatment and expenditures on psychotropic drugs among children in the welfare system. Methods: Child participants (N=4,453) in the first National Survey of Child and Adolescent Well-Being (NSCAW) were linked to their Medicaid claims from 36 states. Three specifications for severity of maltreatment were developed. A two-part regression of logistic and generalized linear models of expenditures on psychotropic medications was estimated for each specification. Results: Physically abused children had higher odds (odds ratio [OR]=1.34) and neglected children had lower odds (OR=.76) of incurring psychotropic drug expenditures. Children who experienced the most severe level of harm had higher odds (OR=1.33) of medication use, compared with children without appreciable harm. No maltreatment specifications were associated with increased expenditures on psychotropic drugs. Conclusions: The magnitude of maltreatment affected odds of use of psychotropic drugs but had no effect on Medicaid expenditures for these drugs.


Document Type: Article
Source: Scopus

 

 

October 13, 2016

1) 

Monasterio, E.a , Mei-Dan, O.b , Hackney, A.C.c , Lane, A.R.c , Zwir, I.d , Rozsa, S.d , Cloninger, C.R.d
Stress reactivity and personality in extreme sport athletes: The psychobiology of BASE jumpers
(2016) Physiology and Behavior, 167, pp. 289-297. 

DOI: 10.1016/j.physbeh.2016.09.025


a University of Otago, Hillmorton Hospital, Private Bag, Christchurch, New Zealand
b Department of Orthopedics, University of Colorado, CU Sports Medicine and Performance Center, Boulder, CO, United States
c Department of Exercise & Sport Science, University of North Carolina, Chapel Hill, NC, United States
d Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 South Euclid Avenue, St. Louis, MO, United States


Abstract
This is the first report of the psychobiology of stress in BASE jumpers, one of the most dangerous forms of extreme sport. We tested the hypotheses that indicators of emotional style (temperament) predict salivary cortisol reactivity, whereas indicators of intentional goal-setting (persistence and character) predict salivary alpha-amylase reactivity during BASE jumping. Ninety-eight subjects completed the Temperament and Character Inventory (TCI) the day before the jump, and 77 also gave salivary samples at baseline, pre-jump on the bridge over the New River Gorge, and post-jump upon landing. Overall BASE jumpers are highly resilient individuals who are highly self-directed, persistent, and risk-taking, but they are heterogeneous in their motives and stress reactivity in the Hypothalamic-Pituitary-Adrenal (HPA) stress system (cortisol reactivity) and the sympathetic arousal system (alpha-amylase reactivity). Three classes of jumpers were identified using latent class analysis based on their personality profiles, prior jumping experience, and levels of cortisol and alpha-amylase at all three time points. “Masterful” jumpers (class 1) had a strong sense of self-directedness and mastery, extensive prior experience, and had little alpha-amylase reactivity and average cortisol reactivity. “Trustful” jumpers (class 2) were highly cooperative and trustful individuals who had little cortisol reactivity coincident with the social support they experienced prior to jumping. “Courageous” jumpers (class 3) were determined despite anxiety and inexperience, and they had high sympathetic reactivity but average cortisol activation. We conclude that trusting social attachment (Reward Dependence) and not jumping experience predicted low cortisol reactivity, whereas persistence (determination) and not jumping experience predicted high alpha-amylase reactivity. © 2016 The Authors


Author Keywords
BASE jumping;  Character;  Extreme sports;  Resilience;  Stress reactivity;  Temperament


Document Type: Article
Source: Scopus




2) 

Semenkovich, K.a , Bischoff, A.b , Doty, T.b , Nelson, S.a , Siller, A.F.c , Hershey, T.b d e , Arbeláez, A.M.a f
Clinical presentation and memory function in youth with type 1 diabetes
(2016) Pediatric Diabetes, 17 (7), pp. 492-499. 

DOI: 10.1111/pedi.12314


a Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
e Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
f St. Louis Children’s Hospital, St Louis, MO, United States


Abstract
Objective: While cerebral edema and diabetic ketoacidosis (DKA) in type 1 diabetes (T1DM) have well-described acute effects on cognition, little is known about the impact of clinical presentation on longer term cognitive outcomes. We hypothesized that clinical factors (degree of hyperglycemia exposure and DKA) at the time of diagnosis would relate to cognition within 3.5 months later in children with T1DM. Methods: Cognitive testing was performed on children 7–17 years old with T1DM (n = 66) within 3.5 months of diagnosis and siblings without T1DM (n = 33). Overall intelligence, processing speed, and memory (including a sensitive long-delay spatial memory test; spatial delayed response or SDR) were assessed. Medical records were reviewed for hemoglobin A1c (HbA1c), DKA status, and other clinical factors at diagnosis. Results: Within the group with T1DM, 17 children presented in DKA and 49 did not. After adjusting for age, gender, and socioeconomic status, the subgroup with T1DM and DKA at diagnosis performed worse on the long-delay SDR task compared to sibling controls (p = 0.006). In addition, within the group with T1DM, higher HbA1c at diagnosis was associated with worse performance on the long-delay SDR task (p = 0.027). Performance on the other cognitive tasks was not different across groups or subgroups. Conclusions: DKA and degree of hyperglycemia exposure at diagnosis have implications for long-delay spatial memory function within 3.5 months of diagnosis. These findings suggest that early detection of T1DM, which decreases risk for prolonged exposure to hyperglycemia and DKA, may avoid negative effects on memory function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


Author Keywords
cognition;  diabetes mellitus;  DKA


Document Type: Article
Source: Scopus




3) 

Ibrahim, A.a , Hor, S.b , Bahar, O.S.c , Dwomoh, D.a , McKay, M.M.c e , Esena, R.K.a , Agyeponge, I.A.a d
Pathways to psychiatric care for mental disorders: A retrospective study of patients seeking mental health services at a public psychiatric facility in Ghana
(2016) International Journal of Mental Health Systems, 10 (1), art. no. 63, . 

DOI: 10.1186/s13033-016-0095-1


a University of Ghana, School of Public Health, P.O. Box LG13, Accra, Ghana
b Catholic Relief Services, RT 70 Gumani Residential Area, Tamale, Ghana
c Silver School of Social Work, New York University, New York, NY, United States
d Ghana Health Service, Private Mail Bag, Ministries, Accra, Ghana
e Washington University in St. Louis, The Brown School, St. Louis, MO, United States


Abstract
Background: The process to seek for care by patients who experience episodes of mental disorders may determine how and where they receive the needed treatment. This study aimed to understand the pathways that people with mental disorders traversed for psychiatric services, particularly where these individuals will first seek treatment and the factors that influence such pathways to mental health care. Methods: A cross-sectional study conducted at Pantang psychiatric hospital in Accra, Ghana involving 107 patients of ages 18 and older and their family members. The study adapted the World Health Organization's (WHO) pathway encounter form to collect information about patients' pathway contacts for psychiatric care. Chi Square test was done to determine patients' first point of contact and any association between the independent variables (clinical diagnosis and socio-demographic factors) and first pathway contact. Multiple regression analyses were also done to estimate the odds of patients' first pathway contact. Results: Overall, nearly 48 % of patients initially contacted non-psychiatric treatment centers (faith-based, traditional healers and general medical practitioners) as their first point of contact for treatment of mental disorders. A little more than half of the patients went directly to the formal public psychiatric facility as their first point of contact for care of their mental disorders. Patients' occupation was significantly associated with their first point of contact for psychiatric care (χ 2 = 6.91; p &lt; 0.033). Those with secondary education were less likely to initially seek care from the formal public psychiatric hospital compared to those with no formal education (uOR = 0.86; 95 % CI 0.18-4.08). Conclusion: Patients used different pathways to seek psychiatric care, namely direct pathway to a psychiatric hospital or through transition from informal non-psychiatric service providers. Since nearly half of patients do not initially seek mental health care directly at the formal psychiatric facility, it is important for the government of Ghana to increase funding to the mental health authorities in Ghana as a matter of priority so that more individuals can be identified and integrated into mainstream psychiatric treatment and general health facilities where there are trained Community Mental Health Officers (CMHO) and Clinical Psychiatric Officers (CPO) to provide early intervention and treatment. © 2016 The Author(s).


Author Keywords
Ghana;  Mental disorders;  Pantang Psychiatric Hospital;  Pathways to care


Document Type: Article
Source: Scopus




4) 

Schwetye, K.E.a , Joseph, N.M.d , Al-Kateb, H.a , Rich, K.M.c , Schmidt, R.E.a , Perry, A.d , Gutmann, D.H.b , Dahiya, S.a
Gliosarcomas lack BRAFV600E mutation, but a subset exhibit β-catenin nuclear localization
(2016) Neuropathology, 36 (5), pp. 448-455. 

DOI: 10.1111/neup.12293


a Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pathology, University of California-San Francisco, San Francisco, CA, United States


Abstract
Gliosarcoma (GS) is a rare subtype of glioblastoma (GBM) characterized by both glial and mesenchymal components. Unlike GBM, there are no specific prognostic markers, and optimized treatments for patients with GS do not exist. Recent reports describe BRAFV600E mutation in malignant peripheral nerve sheath tumors, and aberrant Wnt signaling and CTNNB1 (β-catenin gene) mutations have been described in GBM. We sought to determine whether GS tumors harbor BRAFV600E mutations or aberrant Wnt signaling, as indicated by nuclear localization of β-catenin, by immunohistochemical detection. Forty-eight (48) cases of primary and secondary adult GS (including recurrent ones) were evaluated by immunohistochemical techniques for the presence of nuclear β-catenin and the BRAFV600E mutation. A small subset (6/46, 13%) showed nuclear localization of β-catenin. None of the cases harbored BRAFV600E mutations (0/48). These results are the first to describe the presence of Wnt signaling pathway abnormalities, manifested by nuclear β-catenin, in a subset, as well as the lack of BRAFV600E mutation in GS. We propose a potential role for Wnt pathway alterations in the pathogenesis of a subset of GS. © 2016 Japanese Society of Neuropathology.


Author Keywords
beta-catenin;  BRAF-V600E;  glioblastoma;  gliosarcoma;  WNT pathway


Document Type: Article
Source: Scopus




5) 

Coffman, D.L.a d , Balantekin, K.N.b , Savage, J.S.c
Using Propensity Score Methods to Assess Causal Effects of Mothers' Dieting Behavior on Daughters' Early Dieting Behavior
(2016) Childhood Obesity, 12 (5), pp. 334-340. 

DOI: 10.1089/chi.2015.0249


a Methodology Center, Pennsylvania State University, University Park, PA, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Center for Childhood Obesity Research, Pennsylvania State University, University Park, PA, United States
d Department of Epidemiology and Biostatistics, Temple University, 1301 Cecil B. Moore Avenue, Philadelphia, PA, United States


Abstract
Background: A high prevalence of dieting has been reported among preadolescent females. It is important to understand factors influencing the emergence of dieting because dieting is associated with increased likelihood of overeating, greater weight gain over time, and other chronic health problems. Previous studies suggest that mothers' own dieting behavior influences their daughters' dieting (i.e., modeling). Because it is not possible to randomly assign girls to a mother who is dieting versus not dieting, causal inference regarding the effects of mothers' modeling behaviors on daughters' dieting is not straightforward. Methods: In an observational study, data were collected on four occasions of measurement across a 6-year period, with 2-year intervals between assessments on 181 girls and their parents. Propensity score methods were used to estimate the causal effects of mothers' dieting on the emergence of daughters' dieting between ages 7 and 11, examining the moderating effect of weight status. Results: Girls whose mothers were currently dieting were significantly more likely to diet before age 11 than those whose mothers were not currently dieting, and this effect did not vary by girls' or mothers' weight status. Conclusions: We conclude by discussing the implications of the effects of mothers' dieting on daughters' early dieting as well as the potential of propensity score methods in the field of obesity compared with traditional methodology such as regression analysis. © Copyright 2016, Mary Ann Liebert, Inc. 2016.


Document Type: Article
Source: Scopus




6) 

Kelly, T.F.a c , Simmons, J.P.b
When does making detailed predictions make predictions worse?
(2016) Journal of Experimental Psychology: General, 145 (10), pp. 1298-1311. 

DOI: 10.1037/xge0000204


a Olin Business School, Washington University, St. Louis, WA, United States
b The Wharton School, University of PennsylvaniaPA, United States
c RAND Corporation, Pittsburgh, PA, United States


Abstract
In this article, we investigate whether making detailed predictions about an event worsens other predictions of the event. Across 19 experiments, 10,896 participants, and 407,045 predictions about 724 professional sports games, we find that people who made detailed predictions about sporting events (e.g., how many hits each baseball team would get) made worse predictions about more general outcomes (e.g., which team would win). We rule out that this effect is caused by inattention or fatigue, thinking too hard, or a differential reliance on holistic information about the teams. Instead, we find that thinking about game-relevant details before predicting winning teams causes people to give less weight to predictive information, presumably because predicting details makes useless or redundant information more accessible and thus more likely to be incorporated into forecasts. Furthermore, we show that this differential use of information can be used to predict what kinds of events will and will not be susceptible to the negative effect of making detailed predictions. © 2016 American Psychological Association.


Author Keywords
Accessibility;  Decision making;  Forecasting accuracy;  Prediction specificity


Document Type: Article
Source: Scopus




7) 

Xuan, Z.a , Naimi, T.S.b , Kaplan, M.S.c , Bagge, C.L.d , Few, L.R.e , Maisto, S.f , Saitz, R.a , Freeman, R.g
Alcohol Policies and Suicide: A Review of the Literature
(2016) Alcoholism: Clinical and Experimental Research, 40 (10), pp. 2043-2055. 

DOI: 10.1111/acer.13203


a Department of Community Health Sciences, Boston University School of Public Health, Boston, MA, United States
b Section of General Internal Medicine, Boston Medical Center, Boston, MA, United States
c Department of Social Welfare, Luskin School of Public Affairs, University of California Los Angeles, Los Angeles, CA, United States
d Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, United States
e Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
f Department of Psychology, Syracuse University, Syracuse, NY, United States
g National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, United States


Abstract
Both intoxication and chronic heavy alcohol use are associated with suicide. There is extensive population-level evidence linking per capita alcohol consumption with suicide. While alcohol policies can reduce excessive alcohol consumption, the relationship between alcohol policies and suicide warrants a critical review of the literature. This review summarizes the associations between various types of alcohol policies and suicide, both in the United States and internationally, as presented in English-language literature published between 1999 and 2014. Study designs, methodological challenges, and limitations in ascertaining the associations are discussed. Because of the substantial between-states variation in alcohol policies, U.S.-based studies contributed substantially to the literature. Repeated cross-sectional designs at both the ecological level and decedent level were common among U.S.-based studies. Non-U.S. studies often used time series data to evaluate pre–post comparisons of a hybrid set of policy changes. Although inconsistency remained, the published literature in general supported the protective effect of restrictive alcohol policies on reducing suicide as well as the decreased level of alcohol involvement among suicide decedents. Common limitations included measurement and selection bias and a focus on effects of a limited number of alcohol policies without accounting for other alcohol policies. This review summarizes a number of studies that suggest restrictive alcohol policies may contribute to suicide prevention on a general population level and to a reduction of alcohol involvement among suicide deaths. Copyright © 2016 by the Research Society on Alcoholism


Author Keywords
Alcohol Policies;  Blood Alcohol Content;  Critical Review;  Suicide


Document Type: Review
Source: Scopus




8) 

Murphy, E.R.a , Norr, M.b , Strang, J.F.c , Kenworthy, L.c , Gaillard, W.D.c , Vaidya, C.J.c d
Neural Basis of Visual Attentional Orienting in Childhood Autism Spectrum Disorders
(2016) Journal of Autism and Developmental Disorders, pp. 1-10. Article in Press. 

DOI: 10.1007/s10803-016-2928-9


a Department of Psychiatry, Washington University in St. Louis, 4444 Forest Park Parkway, Suite 2100, St Louis, MO, United States
b Department of Psychology, University of California, Berkley, Berkley, United States
c Children’s Research Institute, Children’s National Medical Center, Washington, United States
d Department of Psychology, 306 White-Gravenor Hall, Georgetown University, 37th and O Street, NW, Washington, DC, United States


Abstract
We examined spontaneous attention orienting to visual salience in stimuli without social significance using a modified Dot-Probe task during functional magnetic resonance imaging in high-functioning preadolescent children with Autism Spectrum Disorder (ASD) and age- and IQ-matched control children. While the magnitude of attentional bias (faster response to probes in the location of solid color patch) to visually salient stimuli was similar in the groups, activation differences in frontal and temporoparietal regions suggested hyper-sensitivity to visual salience or to sameness in ASD children. Further, activation in a subset of those regions was associated with symptoms of restricted and repetitive behavior. Thus, atypicalities in response to visual properties of stimuli may drive attentional orienting problems associated with ASD. © 2016 Springer Science+Business Media New York


Author Keywords
Attention orienting;  Autism spectrum disorder;  fMRI;  Restricted and repetitive behavior;  Visual salience


Document Type: Article in Press
Source: Scopus




9) 

Dhand, A.a b , Luke, D.A.c , Lang, C.E.d , Lee, J.-M.e
Social networks and neurological illness
(2016) Nature Reviews Neurology, 12 (10), pp. 605-612. 

DOI: 10.1038/nrneurol.2016.119


a Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 45 Francis Street, United States
b Network Science Institute, Northeastern University, 177 Huntington Avenue, 11th Floor, Boston, MA, United States
c Center for Public Health Systems Science, George Warren Brown School of Social Work, Washington University in St. Louis, Campus BOX 1196, One Brookings Drive, St. Louis, MO, United States
d Program in Physical Therapy, Washington University School of Medicine, Box 8502, 4444 Forest Park Avenue, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St. Louis, MO, United States


Abstract
Every patient is embedded in a social network of interpersonal connections that influence health outcomes. Neurologists routinely need to engage with a patient's family and friends due to the nature of the illness and its social sequelae. Social isolation is a potent determinant of poor health and neurobiological changes, and its effects can be comparable to those of traditional risk factors. It would seem reasonable, therefore, to map and follow the personal networks of neurology patients. This approach reveals influential people, their habits, and linkage patterns that could facilitate or limit health behaviours. Personal network information can be particularly valuable to enhance risk factor management, medication adherence, and functional recovery. Here, we propose an agenda for research and clinical practice that includes mapping the networks of patients with diverse neurological disorders, evaluating the impact of the networks on patient outcomes, and testing network interventions. © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.


Document Type: Review
Source: Scopus




10) 

Christofoletti, G.a b , McNeely, M.E.b c , Campbell, M.C.c d , Duncan, R.P.b c , Earhart, G.M.b c e
Investigation of factors impacting mobility and gait in Parkinson disease
(2016) Human Movement Science, 49, pp. 308-314. 

DOI: 10.1016/j.humov.2016.08.007


a Federal University of Mato Grosso do Sul, Program in Health and Development, Campo Grande, MS, Brazil
b Washington University School of Medicine in Saint Louis, Program in Physical Therapy, St. Louis, MO, United States
c Washington University School of Medicine in Saint Louis, Department of Neurology, St. Louis, MO, United States
d Washington University School of Medicine in Saint Louis, Department of Radiology, St. Louis, MO, United States
e Washington University School of Medicine in Saint Louis, Department of Neuroscience, St. Louis, MO, United States


Abstract
Mobility and gait limitations are major issues for people with Parkinson disease (PD). Identification of factors that contribute to these impairments may inform treatment and intervention strategies. In this study we investigated factors that predict mobility and gait impairment in PD. Participants with mild to moderate PD and without dementia (n = 114) were tested in one session ‘off’ medication. Mobility measures included the 6-Minute Walk test and Timed-Up-and-Go. Gait velocity was collected in four conditions: forward preferred speed, forward dual task, forward fast as possible and backward walking. The predictors analyzed were age, gender, disease severity, balance, balance confidence, fall history, self-reported physical activity, and executive function. Multiple regression models were used to assess the relationships between predictors and outcomes. The predictors, in different combinations for each outcome measure, explained 55.7% to 66.9% of variability for mobility and 39.5% to 52.8% for gait velocity. Balance was the most relevant factor (explaining up to 54.1% of variance in mobility and up to 45.6% in gait velocity). Balance confidence contributed to a lesser extent (2.0% to 8.2% of variance) in all models. Age explained a small percentage of variance in mobility and gait velocity (up to 2.9%). Executive function explained 3.0% of variance during forward walking only. The strong predictive relationships between balance deficits and mobility and gait impairment suggest targeting balance deficits may be particularly important for improving mobility and gait in people with PD, regardless of an individual's age, disease severity, fall history, or other demographic features. © 2016 Elsevier B.V.


Author Keywords
Balance;  Disease severity;  Executive function;  Gait;  Mobility;  Parkinson disease


Document Type: Article
Source: Scopus




11) 

Kudose, S.a c , Kyriakos, M.a , Awad, M.M.b
Gastric plexiform schwannoma in association with neurofibromatosis type 2
(2016) Clinical Journal of Gastroenterology, pp. 1-6. Article in Press. 

DOI: 10.1007/s12328-016-0687-y


a Division of Surgical Pathology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
c Department of Pathology and Immunology, Washington University, 660 S. Euclid Ave., Campus Box 8118, St. Louis, MO, United States


Abstract
Plexiform schwannoma (PS) is an uncommon variant of schwannoma characterized by a multinodular (plexiform) growth pattern. It comprises up to 5 % of all schwannomas. The association between PS and neurofibromatosis type 1 or type 2 (NF1/NF2) is only rarely reported. Most cases of PS occur in the skin and subcutaneous soft tissue, with only a few reports of digestive tract involvement. We describe an 18-year-old male with NF2 who had bilateral vestibular schwannomas and multiple cutaneous PSs, and a 3-year history of abdominal pain. The patient ultimately underwent a distal gastrectomy for a partially obstructing submucosal antral mass, associated with an overlying ulcer. Histopathologic examination showed the mass to be a PS. The patient is alive and well, without symptoms, 12 months postoperatively. A review of the English language medical literature yielded only ten examples of PS arising in the digestive tract. Our patient is the first to be reported to have a gastric PS, and only the second patient to be reported with a digestive tract PS to have NF2, and the only patient reported to have both digestive tract and cutaneous PSs. Despite its rare occurrence with NF2, the finding of PS at any site should stimulate an examination for other manifestations of this disorder. Clinical Trial Registration: None. © 2016 Japanese Society of Gastroenterology


Author Keywords
Plexiform schwannoma;  Stomach


Document Type: Article in Press
Source: Scopus




12) 

Lee, A.-R.a b , Ko, K.W.a d , Lee, H.a , Yoon, Y.-S.a b c , Song, M.-R.a , Park, C.-S.a b c
Putative cell adhesion membrane protein Vstm5 regulates neuronal morphology and migration in the central nervous system
(2016) Journal of Neuroscience, 36 (39), pp. 10181-10197. 

DOI: 10.1523/JNEUROSCI.0541-16.2016


a School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea
b National Leading Research Laboratory, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea
c GIST Research Institute (GRI), Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea
d Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
During brain development, dynamic changes in neuronal membranes perform critical roles in neuronal morphogenesis and migration to create functional neural circuits. Among the proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V-set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia. Vstm5 also regulates neuronal morphology by promoting dendritic protrusions that later develop into dendritic spines. Using electroporation in utero, we found that Vstm5 overexpression delayed neuronal migration and induced multiple branches in leading processes during corticogenesis. These results indicate that Vstm5 is a new cell-adhesion-like molecule and is critically involved in synaptogenesis and corticogenesis by promoting neuronal membrane dynamics. © 2016 the authors.


Author Keywords
Dendrite;  Dendritic filopodia;  Dendritic spine;  Morphogenesis;  Neuronal migration;  Vstm5


Document Type: Article
Source: Scopus




13) 

Winter, A.C.a , Rist, P.M.b , Buring, J.E.b , Kurth, T.b c
Prospective comorbidity-matched study of Parkinson's disease and risk of mortality among women
(2016) BMJ Open, 6 (9), art. no. A75, . 

DOI: 10.1136/bmjopen-2016-011888


a Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States
c Institute of Public Health, Charité-Universitätsmedizin, Berlin, Germany


Abstract
Background Individuals with Parkinson's disease (PD) may have an increased risk of overall mortality compared to the general population. Women may have lower mortality rates from PD than men; however, studies among women on the effect of PD on mortality have been limited and may not have adequately controlled for confounding by comorbidities. Methods We conducted a matched cohort study among participants in the Women's Health Study. 396 incident PD cases were identified through self-report. Each PD case was matched by age to a comparator who was alive and had the same modified Charlson comorbidity score as the PD case. The PD cases and matched comparators were followed for all-cause mortality. Cox proportional hazards models adjusted for age at the index date, smoking, alcohol consumption, exercise and body mass index were used to determine the association between PD and mortality. Results During a median of 6.2â €..years of follow-up, 72 women died (47 PD cases and 25 comparators). The multivariable-Adjusted HR for mortality was 2.60 (95% CI 1.56 to 4.32). Conclusions PD was associated with more than a twofold increased risk of all-cause mortality among women. Results are similar to those observed among men. © Published by the BMJ Publishing Group Limited.


Author Keywords
EPIDEMIOLOGY;  mortality


Document Type: Article
Source: Scopus




14) 

Putnam, A.L.a , Sungkhasettee, V.W.b , Roediger, H.L., IIIb
Optimizing Learning in College: Tips From Cognitive Psychology
(2016) Perspectives on Psychological Science, 11 (5), pp. 652-660. 

DOI: 10.1177/1745691616645770


a Department of Psychology, Carleton College, United States
b Psychological & Brain Sciences Department, Washington University, St. Louis, United States


Abstract
Every fall, thousands of college students begin their first college courses, often in large lecture settings. Many students, even those who work hard, flounder. What should students be doing differently? Drawing on research in cognitive psychology and our experience as educators, we provide suggestions about how students should approach taking a course in college. We discuss time management techniques, identify the ineffective study strategies students often use, and suggest more effective strategies based on research in the lab and the classroom. In particular, we advise students to space their study sessions on a topic and to quiz themselves, as well as using other active learning strategies while reading. Our goal was to provide a framework for students to succeed in college classes. © 2016, © The Author(s) 2016.


Author Keywords
college success;  learning techniques;  memory;  metacognition;  study strategies


Document Type: Article
Source: Scopus




15) 

Ferrari, M.a , Culver, J.P.b , Hoshi, Y.c , Wabnitz, H.d
Special Section Guest Editorial:Clinical near-infrared spectroscopy and imaging of the brain
(2016) Journal of Biomedical Optics, 21 (9), art. no. 091301, . 

DOI: 10.1117/1.JBO.21.9.091301


a University of l'Aquila, Department of Life, Health and Environmental Sciences, Via Vetoio, L'Aquila, Italy
b Washington University, Department of Radiology, 4525 Scott Avenue, St. Louis, MO, United States
c Hamamatsu University, Institute for Medical Photonics Research, Department of Biomedical Optics, 1-20-1 Handayama, Hamamatsu, Shizuoka, Japan
d Physikalisch-Technische Bundesanstalt (PTB), Department of Biomedical Optics, Abbestr. 2-12, Berlin, Germany


Document Type: Editorial
Source: Scopus




16) 

Rodebaugh, T.L.a , Scullin, R.B.b , Langer, J.K.a , Dixon, D.J.b , Huppert, J.D.c , Bernstein, A.d , Zvielli, A.d , Lenze, E.J.b
Unreliability as a Threat to understanding psychopathology: The cautionary tale of attentional bias
(2016) Journal of Abnormal Psychology, 125 (6), pp. 840-851. 

DOI: 10.1037/abn0000184


a Department of Psychology, Washington University in St. LouisMO, United States
b Department of Psychiatry, Washington University School of MedicineMO, United States
c Department of Psychology, Hebrew University of Jerusalem, Israel
d Department of Psychology, University of Haifa, Israel


Abstract
The use of unreliable measures constitutes a threat to our understanding of psychopathology, because advancement of science using both behavioral and biologically oriented measures can only be certain if such measurements are reliable. Two pillars of the National Institute of Mental Health's portfolio-the Research Domain Criteria (RDoC) initiative for psychopathology and the target engagement initiative in clinical trials-cannot succeed without measures that possess the high reliability necessary for tests involving mediation and selection based on individual differences. We focus on the historical lack of reliability of attentional bias measures as an illustration of how reliability can pose a threat to our understanding. Our own data replicate previous findings of poor reliability for traditionally used scores, which suggests a serious problem with the ability to test theories regarding attentional bias. This lack of reliability may also suggest problems with the assumption (in both theory and the formula for the scores) that attentional bias is consistent and stable across time. In contrast, measures accounting for attention as a dynamic process in time show good reliability in our data. The field is sorely in need of research reporting findings and reliability for attentional bias scores using multiple methods, including those focusing on dynamic processes over time. We urge researchers to test and report reliability of all measures, considering findings of low reliability not just as a nuisance but as an opportunity to modify and improve upon the underlying theory. Full assessment of reliability of measures will maximize the possibility that RDoC (and psychological science more generally) will succeed. © 2016 American Psychological Association.


Author Keywords
Attentional bias;  Personalized medicine;  RDoC;  Reliability;  Target engagement


Document Type: Article
Source: Scopus




17) 

Waller, R.a , Corral-Frías, N.S.b , Vannucci, B.b , Bogdan, R.b , Knodt, A.R.c , Hariri, A.R.c , Hyde, L.W.d
An oxytocin receptor polymorphism predicts amygdala reactivity and antisocial behavior in men
(2016) Social Cognitive and Affective Neuroscience, 11 (8), pp. 1218-1226. 

DOI: 10.1093/scan/nsw042


a Department of Psychology, University of Michigan, Ann Arbor, MI, United States
b Department of Psychological and Brain Sciences, Washington University, St. Louis, WA, United States
c Department of Psychology and Neuroscience, Duke University, Durham, NC, United States
d Department of Psychology, Institute for Social Research, Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, United States


Abstract
Variability in oxytocin (OXT) signaling is associated with individual differences in sex-specific social behavior across species. The effects of OXT signaling on social behavior are, in part, mediated through its modulation of amygdala function. Here, we use imaging genetics to examine sex-specific effects of three single-nucleotide polymorphisms in the human oxytocin receptor gene (OXTR; rs1042778, rs53576 and rs2254298) on threat-related amygdala reactivity and social behavior in 406 Caucasians. Analyses revealed that among men but not women, OXTR rs1042778 TT genotype was associated with increased right amygdala reactivity to angry facial expressions, which was uniquely related to higher levels of antisocial behavior among men. Moderated meditation analysis suggested a trending indirect effect of OXTR rs1042778 TT genotype on higher antisocial behavior via increased right amygdala reactivity to angry facial expressions in men. Our results provide evidence linking genetic variation in OXT signaling to individual differences in amygdala function. The results further suggest that these pathways may be uniquely important in shaping antisocial behavior in men. © The Author (2016).


Author Keywords
Aggression;  Amygdala;  Neuroimaging;  Neuroscience;  OXTR;  Oxytocin;  Psychopathology;  rs1042778;  Violence


Document Type: Article
Source: Scopus




18) 

Bollich, K.L.a , Doris, J.M.b , Vazire, S.c , Raison, C.L.d e , Jackson, J.J.a , Mehl, M.R.f
Eavesdropping on character: Assessing everyday moral behaviors
(2016) Journal of Research in Personality, 61, pp. 15-21. 

DOI: 10.1016/j.jrp.2015.12.003


a Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
b Department of Philosophy and Philosophy–Neuroscience–Psychology Program, Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychology, University of California, Davis, CA, United States
d Department of Human Development and Family Studies, School of Human Ecology, University of Wisconsin-Madison, Madison, WI, United States
e Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
f Department of Psychology, University of Arizona, Tucson, AZ, United States


Abstract
Despite decades of interest in moral character, comparatively little is known about moral behavior in everyday life. This paper reports a novel method for assessing everyday moral behaviors using the Electronically Activated Recorder (EAR)—a digital audio-recorder that intermittently samples snippets of ambient sounds from people's environments—and examines the stability of these moral behaviors. In three samples (combined N = 186), participants wore an EAR over one or two weekends. Audio files were coded for everyday moral behaviors (e.g., showing sympathy, gratitude) and morally-neutral comparison language behaviors (e.g., use of prepositions, articles). Results indicate that stable individual differences in moral behavior can be systematically observed in daily life, and that their stability is comparable to the stability of neutral language behaviors. © 2016 Elsevier Inc.


Author Keywords
Ambulatory assessment;  Electronically Activated Recorder (EAR);  Moral behavior;  Moral character;  Naturalistic observation;  Personality;  Temporal stability


Document Type: Article
Source: Scopus




19) 

Chatterjee, P.a b c , Gupta, V.B.b c , Fagan, A.M.f i , Jasielec, M.S.g i , Xiong, C.g i , Sohrabi, H.R.a b c , Dhaliwal, S.d , Taddei, K.b c , Bourgeat, P.e , Brown, B.M.a b c , Benzinger, T.h i , Bateman, R.J.f i , Morris, J.C.f i , Martins, R.N.a b c , Dominantly Inherited Alzheimer Networkj
Decreased platelet APP isoform ratios in autosomal dominant Alzheimer’s disease: Baseline data from a DIAN cohort subset
(2015) Current Alzheimer Research, 12 (2), pp. 157-164. 

DOI: 10.2174/1567205012666150204125732


a School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia
b School of Medical Sciences, Edith Cowan University, Perth, Australia
c TheMcCusker Alzheimer’s Research Foundation, Perth, Australia
d School of Public Health, Curtin University, Perth, Australia
e The Australian e-Health Research Centre, CSIRO, Royal Brisbane and Women’s Hospital, Brisbane, Australia
f Department of Neurology, Washington University, St. Louis, United States
g Division of Biostatistics, Washington University, St. Louis, United States
h Department of Radiology, Washington University, St. Louis, United States
i Knight Alzheimer’s Disease Research Center, Washington University, St. Louis, United States


Abstract
Introduction: This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer’s disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small sample size in both studies. The current study examines APPr in MC versus NC in a larger sample. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study. Methods: APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson’s correlation coefficient (r). Results: APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505; p<0.05) and Precuneus (r=-0.510; p<0.05). Conclusion: APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further. © 2015 Bentham Science Publishers.


Author Keywords
Alzheimer’s disease;  Amyloid precursor protein;  Biomarkers;  Neuropsychological tests;  Pittsburgh compound B;  Platelets


Document Type: Article
Source: Scopus




 

20) 

Musiek, E.S.a , Xiong, D.D.b , Holtzman, D.M.c
Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease
(2015) Experimental & molecular medicine, 47, p. e148. 

DOI: 10.1038/emm.2014.121


a Department of Neurology, Hope Center for Neurological Disorders Research & Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA
b Department of Neurology, Hope Center for Neurological Disorders Research & Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA
c Department of Neurology, Hope Center for Neurological Disorders Research & Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA


Abstract
Disturbances in the sleep-wake cycle and circadian rhythms are common symptoms of Alzheimer Disease (AD), and they have generally been considered as late consequences of the neurodegenerative processes. Recent evidence demonstrates that sleep-wake and circadian disruption often occur early in the course of the disease and may even precede the development of cognitive symptoms. Furthermore, the sleep-wake cycle appears to regulate levels of the pathogenic amyloid-beta peptide in the brain, and manipulating sleep can influence AD-related pathology in mouse models via multiple mechanisms. Finally, the circadian clock system, which controls the sleep-wake cycle and other diurnal oscillations in mice and humans, may also have a role in the neurodegenerative process. In this review, we examine the current literature related to the mechanisms by which sleep and circadian rhythms might impact AD pathogenesis, and we discuss potential therapeutic strategies targeting these systems for the prevention of AD.


Document Type: Review
Source: Scopus

October 6, 2016

1) Stamatakis, K.A.a , Ferreira Hino, A.A.b , Allen, P.c , McQueen, A.d , Jacob, R.R.c , Baker, E.A.e , Brownson, R.C.c 

Results from a psychometric assessment of a new tool for measuring evidence-based decision making in public health organizations

(2017) Evaluation and Program Planning, 60, pp. 17-23. 

 

DOI: 10.1016/j.evalprogplan.2016.08.002

 

a Department of Epidemiology, College for Public Health & Social Justice, Saint Louis University, 3545 Lafayette Avenue, St. Louis, MO, United States

b Department of Physical Education, School of Health and Biosciences, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil

c Prevention Research Center in St. Louis, Brown School, Washington University in St. Louis, One Brookings Drive, St. Louis, MO, United States

d Health Communications Research Laboratory, Washington University in St. Louis, 700 Rosedale Avenue, St. Louis, MO, United States

e Department of Behavioral Science and Health Education, College for Public Health and Social Justice, Saint Louis University, 3545 Lafayette Ave., St Louis, MO, United States

 

Abstract

Background In order to better understand how to improve evidence-based decision making (EBDM) in state health departments, measurement tools are needed to evaluate changes in EBDM. The purpose of this study was to test the psychometric properties of a new measurement tool to assess EBDM in public health practice settings. Methods A questionnaire was developed, pilot-tested and refined in an iterative process with the input of public health practitioners with the aim of identifying a set of specific measures representing different components of EBDM. Data were collected in a national survey of state health department chronic disease practitioners. The final dataset (n = 879) for psychometric testing was comprised of 19 EBDM items that were first examined using exploratory factor analysis, and then confirmatory factor analysis. Results The final model from confirmatory factor analysis includes five latent factors representing components of EBDM: capacity for evaluation, expectations and incentives for EBDM, access to evidence and resources for EBDM, participatory decision making, and leadership support and commitment. Conclusions This study addresses the need for empirically tested and theory-aligned measures that may be used to assess the extent to which EBDM is currently implemented, and further, to gauge the success of strategies to improve EBDM, in public health settings. This EBDM measurement tool may help identify needed supports for enhanced capacity and implementation of effective strategies. © 2016

 

Author Keywords

Confirmatory factor analysis;  Evidence-based decision making;  Measurement;  Public health

 

Document Type: Article

Source: Scopus

 

 

2) Nygard, S.K.a b c , Klambatsen, A.a b , Balouch, B.a , Quinones-Jenab, V.a b , Jenab, S.a b 

NMDAR dependent intracellular responses associated with cocaine conditioned place preference behavior

(2017) Behavioural Brain Research, 317, pp. 218-225. 

 

DOI: 10.1016/j.bbr.2016.09.047

 

a Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY, United States

b Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY, United States

c Department of Anesthesiology, Washington University School of Medicine in St. Louis, 660 So. Euclid Avenue, Campus Box 8054, St. Louis, MO, United States

 

Abstract

The aim of this study was to investigate the intracellular responses associated with the acquisition and expression of cocaine-context associations. ERK (extracellular regulated kinase), CREB (cAMP responsive element binding protein), FosB and ΔFosB proteins were of particular interest due to their involvement in cocaine reward and in synaptic plasticity underlying learning and memory. We used the conditioned place preference (CPP) paradigm, which employs a Pavlovian conditioning procedure to establish an association between a drug-paired environment and the drug's rewarding effects, to study the role of these signaling pathways in cocaine-context associations. N-methyl-D-aspartate receptor (NMDAR) antagonism prior to cocaine administration during conditioning blocked the acquisition of cocaine CPP and reduced Nucleus Accumbens (NAc) phosphorylated-ERK (pERK) and phosphorylated CREB (pCREB) levels following the CPP test (drug-free). We also show that cocaine-induced increases in Caudate Putamen (CPu) FosB and ΔFosB levels are decreased after MK-801 pre-treatment during conditioning. In addition, our results provide evidence for the involvement of striatal SIRT (Silent Information Regulator of Transcription) proteins in cocaine-CPP. These results will aid in the advancement of general knowledge about the molecular formation and retrieval of cocaine-associated memories that can be used in the future when designing treatments for cocaine addiction that target both prevention and relapse. © 2016 Elsevier B.V.

 

Author Keywords

Caudate putamen;  Cocaine;  Conditioned place preference;  NMDARs;  Nucleus accumbens

 

Document Type: Article

Source: Scopus

 

 

3) Mann, F.D.a , Engelhardt, L.a , Briley, D.A.b , Grotzinger, A.D.a , Patterson, M.W.a , Tackett, J.L.c , Strathan, D.B.d , Heath, A.e , Lynskey, M.f , Slutske, W.g , Martin, N.G.h , Tucker-Drob, E.M.a i , Harden, K.P.a i 

Sensation seeking and impulsive traits as personality endophenotypes for antisocial behavior: Evidence from two independent samples

(2017) Personality and Individual Differences, 105, pp. 30-39. 

 

DOI: 10.1016/j.paid.2016.09.018

 

a Department of Psychology, University of Texas at Austin, Austin, TX, United States

b Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL, United States

c Department of Psychology, Northwestern University, Evanston, IL, United States

d Faculty of Arts and Business, University of the Sunshine Coast, Sippy Downs, Queensland, Australia

e Psychiatry, Washington University School of Medicine, St Louis, MI, United States

f Institute of Psychiatry, King's College London, London, United Kingdom

g Department of Psychological Sciences, University of Missouri, Columbia, MO, United States

h Genetic Epidemiology, Molecular Epidemiology and Neurogenetics Laboratories, Queensland Institute of Medial Research, Brisbane, Queensland, Australia

i Population Research Center, University of Texas at Austin, Austin, TX, United States

 

Abstract

Sensation seeking and impulsivity are personality traits that are correlated with risk for antisocial behavior (ASB). This paper uses two independent samples of twins to (a) test the extent to which sensation seeking and impulsivity statistically mediate genetic influence on ASB, and (b) compare this to genetic influences accounted for by other personality traits. In Sample 1, delinquent behavior, as well as impulsivity, sensation seeking and Big Five personality traits, were measured in adolescent twins from the Texas Twin Project. In Sample 2, adult twins from the Australian Twin Registry responded to questionnaires that assessed individual differences in Eysenck's and Cloninger's personality dimensions, and a structured telephone interview that asked participants to retrospectively report DSM-defined symptoms of conduct disorder. Bivariate quantitative genetic models were used to identify genetic overlap between personality traits and ASB. Across both samples, novelty/sensation seeking and impulsive traits accounted for larger portions of genetic variance in ASB than other personality traits. We discuss whether sensation seeking and impulsive personality are causal endophenotypes for ASB, or merely index genetic liability for ASB. © 2016 Elsevier Ltd

 

Author Keywords

Antisocial behavior;  Endophenotype;  Impulsivity;  Novelty seeking;  Sensation seeking

 

Document Type: Article

Source: Scopus

 

 

4) Byrne, M.E.a , Eichen, D.M.a b , Fitzsimmons-Craft, E.E.a , Taylor, C.B.c d , Wilfley, D.E.a 

Perfectionism, emotion dysregulation, and affective disturbance in relation to clinical impairment in college-age women at high risk for or with eating disorders

(2016) Eating Behaviors, 23, pp. 131-136. 

 

DOI: 10.1016/j.eatbeh.2016.09.004

 

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

b Department of Pediatrics, University of California, San Diego, CA, United States

c Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States

d Department of Psychiatry and Behavioral Sciences, Palo Alto University, Palo Alto, CA, United States

 

Abstract

Individuals with eating disorders (EDs) demonstrate impaired quality of life; however, less than one-third report severe clinical impairment. Thus, it is important to determine factors that may identify those who are most likely to report marked impairment. Perfectionism, emotion dysregulation, and aspects of affective disturbance, such as anxiety and depression, are independently associated with eating pathology and clinical impairment in eating and other disorders. However, little research has explored these three factors concurrently in relation to eating pathology. It is possible that the combined interaction effect of these constructs could be especially harmful. The current study examined the influence of these constructs and their interactions on clinical impairment in college-aged women at high risk for or with a DSM-5 clinical or subclinical ED. Although the three-way interaction of perfectionism, emotion dysregulation, and affective disturbance (i.e., anxiety or depression) was not significant, the two-way interaction between perfectionism and emotion dysregulation was significant such that those who were high in both perfectionism and emotion dysregulation reported the highest levels of clinical impairment. This suggests that the combination of perfectionism and emotion dysregulation may be especially problematic for those with or at high risk for EDs. Interestingly, perfectionism alone was not a predictor of clinical impairment when accounting for the other constructs, implying that perfectionism may have a greater impact when in conjunction with emotion dysregulation. Understanding the impact of combined perfectionistic tendencies and emotion dysregulation on clinical impairment may better inform treatment and more directly target contributors to impaired quality of life. © 2016 Elsevier Ltd

 

Author Keywords

Anxiety;  Clinical impairment;  Depression;  Eating disorders;  Emotion regulation;  Perfectionism

 

Document Type: Article

Source: Scopus

 

 

5) Hayes, J.F.a , Altman, M.a , Kolko, R.P.b , Balantekin, K.N.a , Holland, J.C.a , Stein, R.I.c , Saelens, B.E.d , Welch, R.R.a , Perri, M.G.e , Schechtman, K.B.f , Epstein, L.H.g , Wilfley, D.E.a 

Decreasing food fussiness in children with obesity leads to greater weight loss in family-based treatment

(2016) Obesity, 24 (10), pp. 2158-2163. 

 

DOI: 10.1002/oby.21622

 

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

b Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States

c Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, United States

d Seattle Children's Research Institute, Seattle, WA, United States

e Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, United States

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

g Department of Pediatrics, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, United States

 

Abstract

Objective: Food fussiness (FF), or the frequent rejection of both familiar and unfamiliar foods, is common among children and, given its link to poor diet quality, may contribute to the onset and/or maintenance of childhood obesity. This study examined child FF in association with anthropometric variables and diet in children with overweight/obesity participating in family-based behavioral weight loss treatment (FBT). Change in FF was assessed in relation to FBT outcome, including whether change in diet quality mediated the relation between change in FF and change in child weight. Methods: Child (N = 170; age = 9.41 ± 1.23) height and weight were measured, and parents completed FF questionnaires and three 24-h recalls of child diet at baseline and post-treatment. Healthy Eating Index-2005 scores were calculated. Results: At baseline, child FF was related to lower vegetable intake. Average child FF decreased from start to end of FBT. Greater decreases in FF were associated with greater reductions in child body mass index and improved overall diet quality. Overall, diet quality change through FBT mediated the relation between child FF change and child body mass index change. Conclusions: Children with high FF can benefit from FBT, and addressing FF may be important in childhood obesity treatment to maximize weight outcomes. © 2016 The Obesity Society

 

Document Type: Article

Source: Scopus

 

 

6) Knopik, V.S.a b , Marceau, K.a c , Bidwell, L.C.d , Palmer, R.H.C.a b , Smith, T.F.a e , Todorov, A.f , Evans, A.S.g , Heath, A.C.h 

Smoking during pregnancy and ADHD risk: A genetically informed, multiple-rater approach

(2016) American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 171 (7), pp. 971-981. Cited 1 time.

 

DOI: 10.1002/ajmg.b.32421

 

a Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, United States

b Department of Psychiatry and Human Behavior, Brown University, Providence, RI, United States

c Center for Alcohol and Addiction Studies, Brown University, Providence, RI, United States

d Institute of Cognitive Science, University of Colorado, Boulder, CO, United States

e Department of Psychology and Child Development, California Polytechnic State University, San Luis Obispo, CA, United States

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

g Memorial Hospital, Pawtucket, RI USA; Warren Alpert School of Medicine, Brown University, Providence, RI, United States

h Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States

 

Abstract

Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the developing child, including behavioral outcomes such as Attention–Deficit Hyperactivity Disorder (ADHD). There is substantial interest in understanding the nature of this reported association, particularly in light of more recent genetically informed studies that suggest that the SDP-ADHD link is less clear than once thought. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we use a sibling-comparison approach that controls for shared genetic and familial influences to assess the effects of SDP on ADHD symptom dimensions. ADHD was measured by both parent and teacher report on the Conners report forms and the Child Behavior Checklist/Teacher Report Form (CBCL/TRF). Results for the CBCL/TRF Total ADHD score are consistent with prior genetically informed approaches and suggest that previously reported associations between SDP and ADHD are largely due to familial confounding rather than causal teratogenic effects. However, results from the Conners parent report suggest a potentially causal effect of SDP on hyperactive/impulsive and, to a lesser extent, total ADHD symptoms; SDP results in increased parent-reported hyperactive/impulsive and total ADHD symptoms even after accounting for genetic and familial confounding factors. This suggests that the Conners assessment (parent-report) may provide a sensitive measure for use in studies examining child specific SDP effects on continuous and dimensional aspects of ADHD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

 

Author Keywords

ADHD;  CBCL;  Conners;  genetics;  multiple reporters;  sibling comparison design;  smoking during pregnancy

 

Document Type: Article

Source: Scopus

 

 

7) Valtcheva, M.V.a b c , Copits, B.A.a , Davidson, S.a d , Sheahan, T.D.a c , Pullen, M.Y.a e , McCall, J.G.a , Dikranian, K.f , Gereau, R.W.a 

Surgical extraction of human dorsal root ganglia from organ donors and preparation of primary sensory neuron cultures

(2016) Nature Protocols, 11 (10), pp. 1877-1888. 

 

DOI: 10.1038/nprot.2016.111

 

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

b Medical Scientist Training Program, Washington University in St. Louis, St. Louis, MO, United States

c Neurosciences Program, Washington University in St. Louis, St. Louis, MO, United States

d Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States

e Developmental, Regenerative, and Stem Cell Biology Program, Washington University in St. Louis, St. Louis, MO, United States

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

 

Abstract

Primary cultures of rodent sensory neurons are widely used to investigate the cellular and molecular mechanisms involved in pain, itch, nerve injury and regeneration. However, translation of these preclinical findings may be greatly improved by direct validation in human tissues. We have developed an approach to extract and culture human sensory neurons in collaboration with a local organ procurement organization (OPO). Here we describe the surgical procedure for extraction of human dorsal root ganglia (hDRG) and the necessary modifications to existing culture techniques to prepare viable adult human sensory neurons for functional studies. Dissociated sensory neurons can be maintained in culture for >10 d, and they are amenable to electrophysiological recording, calcium imaging and viral gene transfer. The entire process of extraction and culturing can be completed in <7 h, and it can be performed by trained graduate students. This approach can be applied at any institution with access to organ donors consenting to tissue donation for research, and is an invaluable resource for improving translational research. © 2016 Nature America, Inc. All rights reserved.

 

Document Type: Article

Source: Scopus

 

 

8) Yuan, W.a d j , Harpster, K.c j , Jones, B.V.d j , Shimony, J.S.e , McKinstry, R.C.e , Weckherlin, N.f , Powell, S.S.g h , Barnard, H.i j , Engsberg, J.k , Kadis, D.S.a b j , Dodd, J.g h , Altaye, M.j l , Limbrick, D.D.m , Holland, S.K.a d j , Simpson, S.M.a , Bidwell, S.a , Mangano, F.T.j n 

Changes of White Matter Diffusion Anisotropy in Response to a 6-Week iPad Application-Based Occupational Therapy Intervention in Children with Surgically Treated Hydrocephalus: A Pilot Study

(2016) Neuropediatrics, 47 (5), pp. 336-340. 

 

DOI: 10.1055/s-0036-1584938

 

a Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 5033, Cincinnati, OH, United States

b Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

c Division of Occupational Therapy and Physical Therapy, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

d Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

e Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States

f Cerebral Palsy Center, St. Louis Children's Hospital, St. Louis, MO, United States

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

h Department of Psychology, St. Louis Children's Hospital, St. Louis, MO, United States

i Division of Developmental and Behavioral Pediatrics-Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

j University of Cincinnati, College of Medicine, Cincinnati, OH, United States

k Program in Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States

l Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

m Department of Neurological Surgery, Washington University, School of Medicine, St. Louis, MO, United States

n Division of Pediatric Neurosurgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

 

Abstract

Objective Our aims were (1) to test whether diffusion tensor imaging (DTI) could detect underlying white matter (WM) changes after a 6-week iPad application-based occupational therapy (OT) intervention in children with surgically treated hydrocephalus (HCP); and (2) to explore the association between WM changes and performance outcomes. Methods Five children (age range: 6.05-9.10 years) with surgically treated HCP completed an intensive iPad-based OT intervention targeting common domains of long-term deficits in children with HCP. The intervention included 6 weekly sessions in an OT clinic supplementing home-based program (1 hour/day, 4 days/week). DTI and neuropsychological assessments were performed before and after the intervention. Observation After the therapy, significant increases in fractional anisotropy (FA) and/or decreases in radial diffusivity were found in extensive WM areas. All participants demonstrated an increased perceptual reasoning index (PRI, Wechsler Abbreviated Scale of Intelligence: 2nd edition, PRI gains = 14.20 ± 7.56, p = 0.014). A significant positive correlation was found between PRI increase and the increase of FA in the right posterior limb of the internal capsule and the right external capsule (both p < 0.05). Conclusion This study provides initial evidence of DTI's sensitivity to detect subtle WM changes associated with performance improvements in response to a 6-week OT intervention in children with HCP. © 2016 Georg Thieme Verlag KG Stuttgart. New York.

 

Author Keywords

DTI;  iPad application;  occupational therapy;  pediatric hydrocephalus

 

Document Type: Article

Source: Scopus

 

 

9) Athiraman, U., Todorov, A., Honorato, C., Tempelhoff, R.

A Survey of Incidence of Postoperative Visual Loss Associated With Spine Surgery Outside the United States

(2016) Journal of Neurosurgical Anesthesiology, . Article in Press. 

 

DOI: 10.1097/ANA.0000000000000375

 

Departments of *Anesthesiology §Anesthesiology and Neurological Surgery, Washington University Departments of †Psychiatry ‡Anesthesiology, Washington University School of Medicine, St. Louis, MO

 

Document Type: Article in Press

Source: Scopus

 

 

10) Ishikawa, M.a , Yoshitomi, T.a , Zorumski, C.F.b c d , Izumi, Y.b c d 

24(S)-Hydroxycholesterol protects the ex vivo rat retina from injury by elevated hydrostatic pressure

(2016) Scientific Reports, 6, art. no. 33886, . 

 

DOI: 10.1038/srep33886

 

a Department of Ophthalmology, Akita University Graduate School of Medicine, Akita, Japan

b Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, M.O., United States

c Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, M.O., United States

d Department of Psychiatry, Washington University School of Medicine, St. Louis, M.O., United States

 

Abstract

In the central nervous system, 24(S)-hydroxycholesterol (24(S)-HC) is an oxysterol synthesized from cholesterol by cholesterol 24-hydroxylase (CYP46A1) encoded by the cyp46a1 gene. In the present study using a rat ex vivo glaucoma model, we found that retinal 24(S)-HC synthesis is facilitated by pressure elevation. Moreover, we found that 24(S)-HC is neuroprotective against pressure mediated retinal degeneration. Quantitative real-time RT-PCR, ELISA, and immunohistochemistry revealed that elevated pressure facilitated the expression of cyp46a1 and CYP46A1. Immunohistochemically, the enhanced expression of CYP46A1 was mainly observed in retinal ganglion cells (RGC). LC-MS/MS revealed that 24(S)-HC levels increased in a pressure-dependent manner. Axonal injury and apoptotic RGC death induced by 75 mmHg high pressure was ameliorated by exogenously administered 1 μM 24(S)-HC. In contrast, voriconazole, a CYP46A1 inhibitor, was severely toxic even at normobaric pressure. Under normobaric conditions, 30 μM 24(S)-HC was required to prevent the voriconazole-mediated retinal damage. Taken together, our findings indicate that 24(S)-HC is facilitated by elevated pressure and plays a neuroprotective role under glaucomatous conditions, while voriconazole, an antifungal drug, is retinotoxic. 24(S)-HC and related compounds may serve as potential therapeutic targets for protecting glaucomatous eyes from pressure-induced injuries. © The Author(s) 2016.

 

Document Type: Article

Source: Scopus

 

 

11) Li, K.S., Rempel, D.L., Gross, M.L.

Conformational-Sensitive Fast Photochemical Oxidation of Proteins and Mass Spectrometry Characterize Amyloid Beta 1-42 Aggregation

(2016) Journal of the American Chemical Society, 138 (37), pp. 12090-12098. 

 

DOI: 10.1021/jacs.6b07543

 

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

 

Abstract

Preventing and treating Alzheimer's disease require understanding the aggregation of amyloid beta 1-42 (Aβ1-42) to give oligomers, protofibrils, and fibrils. Here we describe footprinting of Aβ1-42 by hydroxyl radical-based fast photochemical oxidation of proteins (FPOP) and mass spectrometry (MS) to monitor the time-course of Aβ1-42 aggregation. We resolved five distinct stages characterized by two sigmoidal behaviors, showing the time-dependent transitions of monomers-paranuclei-protofibrils-fibrillar aggregates. Kinetic modeling allows deciphering the amounts and interconversion of the dominant Aβ1-42 species. Moreover, the irreversible footprinting probe provides insights into the kinetics of oligomerization and subsequent fibrillar growth by allowing the conformational changes of Aβ1-42 at subregional and even amino-acid-residue levels to be revealed. The middle domain of Aβ1-42 plays a major role in aggregation, whereas the N-terminus retains most of its solvent-accessibility during aggregation, and the hydrophobic C-terminus is involved to an intermediate extent. This approach affords an in situ, real-time monitoring of the solvent accessibility of Aβ1-42 at various stages of oligomerization, and provides new insights on site-specific aggregation of Aβ1-42 for a sample state beyond the capabilities of most other biophysical methods. © 2016 American Chemical Society.

 

Document Type: Article

Source: Scopus

 

 

12) Fernández, M.V., Black, K., Carrell, D., Saef, B., Budde, J., Deming, Y., Howells, B., Del-Aguila, J.L., Ma, S., Bi, C., Norton, J., Chasse, R., Morris, J., Goate, A., Cruchaga, C., NIA-LOAD family study group, NCRAD

SORL1 variants across Alzheimer’s disease European American cohorts

(2016) European Journal of Human Genetics, . Article in Press. 

 

DOI: 10.1038/ejhg.2016.122

 

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

 

Abstract

The accumulation of the toxic Aβ peptide in Alzheimer’s disease (AD) largely relies upon an efficient recycling of amyloid precursor protein (APP). Recent genetic association studies have described rare variants in SORL1 with putative pathogenic consequences in the recycling of APP. In this work, we examine the presence of rare coding variants in SORL1 in three different European American cohorts: early-onset, late-onset AD (LOAD) and familial LOAD.European Journal of Human Genetics advance online publication, 21 September 2016; doi:10.1038/ejhg.2016.122. © 2016 Macmillan Publishers Limited, part of Springer Nature.

 

Document Type: Article in Press

Source: Scopus

 

 

13) Nygard, S.K.a b , Hourguettes, N.J.a , Sobczak, G.G.a , Carlezon, W.A.e , Bruchas, M.R.a c d 

Stress-induced reinstatement of nicotine preference requires dynorphin/kappa opioid activity in the basolateral amygdala

(2016) Journal of Neuroscience, 36 (38), pp. 9937-9948. 

 

DOI: 10.1523/JNEUROSCI.0953-16.2016

 

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

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

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

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

e Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA, United States

 

Abstract

The dynorphin (DYN)/kappa-opioid receptor (KOR) system plays a conserved role in stress-induced reinstatement of drug seeking for prototypical substances of abuse. Due to nicotine’s high propensity for stress-induced relapse, we hypothesized that stress would induce reinstatement of nicotine seeking-like behavior in a KOR-dependent manner. Using a conditioned place preference (CPP) reinstatement procedure in mice, we show that both foot-shock stress and the pharmacological stressor yohimbine (2 mg/kg, i.p.) induce reinstatement of nicotine CPP in a norbinaltorphimine (norBNI, a KOR antagonist)-sensitive manner, indicating that KOR activity is necessary for stress-induced nicotineCPPreinstatement. After reinstatement testing,wevisualized robust c-fos expression in the basolateral amygdala (BLA), which was reduced in mice pretreated with norBNI. We then used several distinct but complementary approaches of locally disrupting BLA KOR activity to assess the role of KORs and KOR-coupled intracellular signaling cascades on reinstatement of nicotine CPP. norBNI injected locally into the BLA prevented yohimbine-induced nicotine CPP reinstatement without affecting CPP acquisition. Similarly, selective deletion of BLA KORs in KOR conditional knock-out mice prevented foot-shock-induced CPP reinstatement. Together, these findings strongly implicate BLA KORs in stress-induced nicotine seeking-like behavior. In addition, we found that chemogenetic activation of Gαi signaling within CaMKIIα BLA neurons was sufficient to induce nicotine CPP reinstatement, identifying an anatomically specific intracellular mechanism by which stress leads to reinstatement. Considered together, our findings suggest that activation of theDYN/KORsystem andGαi signaling within theBLAis both necessary and sufficient to produce reinstatement of nicotine preference. © 2016 the authors.

 

Author Keywords

Basolateral amygdala;  Conditioned place preference;  Kappa opioid receptors;  Nicotine;  Reinstatement;  Stress

 

Document Type: Article

Source: Scopus

 

 

14) Smiley, P.A.a , Buttitta, K.V.b , Chung, S.Y.a d , Coffey, J.K.b e , Wang, B.A.a f , Borelli, J.L.a c 

Anger in response to challenge: children’s emotion socialization predicts approach versus avoidance

(2016) Motivation and Emotion, pp. 1-13. Article in Press. 

 

DOI: 10.1007/s11031-016-9583-5

 

a Department of Psychology, Pomona College, 647 N. College Way, Claremont, CA, United States

b Claremont Graduate University, Claremont, CA, United States

c University of California, Irvine, CA, United States

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

e The University of the South, Sewanee, TN, United States

f Binghamton University (SUNY), Binghamton, NY, United States

 

Abstract

Negative emotion is typically associated with avoidance behavior; however, recent advances in the adult literature show that unlike some emotions (sadness, shame), anger predicts both approach and avoidance. Here we propose that socialization to suppress anger will play a role in whether children who express anger respond to a performance challenge with approach or avoidance. Children (N = 79; Mage = 11.4 years) reported perceptions of parental use of positive conditional regard (PCR) to socialize anger suppression and worked on four unsolvable puzzles. We measured change in verbalized puzzle-solving strategies during failure, and coded emotion expression on the final puzzle. We examined whether negative emotion type (shame/sadness vs. anger) and PCR for anger predicted change in strategy use, and whether the association between level of PCR for anger and approach-avoidance (change in strategy use) depended on type of negative emotion expressed. Neither emotion expression nor level of PCR anger predicted strategy use; however, type of negative emotion moderated the association between PCR anger and change in strategy use, controlling for NCR anger. For children who displayed anger, low PCR was associated with increased strategy use, and high PCR was associated with decreased strategy use. We discuss the role of emotion socialization in shaping approach and avoidance motivation. © 2016 Springer Science+Business Media New York

 

Author Keywords

Anger;  Children;  Emotion suppression;  Positive conditional regard;  Task engagement

 

Document Type: Article in Press

Source: Scopus

 

 

15) Cummings, J.a , Aisen, P.S.b , Dubois, B.c , Frölich, L.d , Jack, C.R., Jr.e , Jones, R.W.f , Morris, J.C.g , Raskin, J.i , Dowsett, S.A.h , Scheltens, P.j 

Drug development in Alzheimer's disease: The path to 2025

(2016) Alzheimer's Research and Therapy, 8 (1), art. no. 39, . 

 

DOI: 10.1186/s13195-016-0207-9

 

a Cleveland Clinic Lou Ruvo, Center for Brain Health, Las Vegas, NV, United States

b University of Southern California, San Diego, CA, United States

c Institute for Memory and Alzheimer's Disease (IM2A), ICM, Salpêtrière University Hospital, Paris University, Paris, France

d Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

e Department of Radiology, Mayo Clinic, Rochester, MN, United States

f Research Institute for the Care of Older People (RICE), Royal United Hospital, Bath, United Kingdom

g Knight Alzheimer Disease Research Center, Washington University, School of Medicine, St Louis, MO, United States

h Eli Lilly and Company, Indianapolis, IN, United States

i Eli Lilly and Company, Toronto, Canada

j Department of Neurology, Alzheimer Center, VU University Medical Center, Amsterdam, Netherlands

 

Abstract

The global impact of Alzheimer's disease (AD) continues to increase, and focused efforts are needed to address this immense public health challenge. National leaders have set a goal to prevent or effectively treat AD by 2025. In this paper, we discuss the path to 2025, and what is feasible in this time frame given the realities and challenges of AD drug development, with a focus on disease-modifying therapies (DMTs). Under the current conditions, only drugs currently in late Phase 1 or later will have a chance of being approved by 2025. If pipeline attrition rates remain high, only a few compounds at best will meet this time frame. There is an opportunity to reduce the time and risk of AD drug development through an improvement in trial design; better trial infrastructure; disease registries of well-characterized participant cohorts to help with more rapid enrollment of appropriate study populations; validated biomarkers to better detect disease, determine risk and monitor disease progression as well as predict disease response; more sensitive clinical assessment tools; and faster regulatory review. To implement change requires efforts to build awareness, educate and foster engagement; increase funding for both basic and clinical research; reduce fragmented environments and systems; increase learning from successes and failures; promote data standardization and increase wider data sharing; understand AD at the basic biology level; and rapidly translate new knowledge into clinical development. Improved mechanistic understanding of disease onset and progression is central to more efficient AD drug development and will lead to improved therapeutic approaches and targets. The opportunity for more than a few new therapies by 2025 is small. Accelerating research and clinical development efforts and bringing DMTs to market sooner would have a significant impact on the future societal burden of AD. As these steps are put in place and plans come to fruition, e.g., approval of a DMT, it can be predicted that momentum will build, the process will be self-sustaining, and the path to 2025, and beyond, becomes clearer. © 2016 The Author(s).

 

Author Keywords

Alzheimer's disease;  Disease-modifying therapy 2025

 

Document Type: Article

Source: Scopus

 

 

16) Carey, C.E.a , Agrawal, A.b , Bucholz, K.K.b , Hartz, S.M.b , Lynskey, M.T.c , Nelson, E.C.b , Bierut, L.J.b , Bogdan, R.a 

Associations between polygenic risk for psychiatric disorders and substance involvement

(2016) Frontiers in Genetics, 7 (AUG), art. no. 149, . 

 

DOI: 10.3389/fgene.2016.00149

 

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

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

c Institute of Psychiatry, King's College London, London, United Kingdom

 

Abstract

Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium's Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the five psychiatric disorders which comprised CROSS-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)-and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p < 0.001). After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: (A) MDD PRS and non-problem cannabis use, (B) MDD PRS and severe cocaine dependence, (C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and (D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity. © 2016 Carey, Agrawal, Bucholz, Hartz, Lynskey, Nelson, Bierut and Bogdan.

 

Author Keywords

Cannabis;  Cocaine;  Comorbidity;  Depression;  Polygenic;  Schizophrenia;  Substance

 

Document Type: Article

Source: Scopus

 

 

17) Killian, N.J.a c , Watkins, P.V.a d , Davidson, L.S.b , Barbour, D.L.a 

The effects of auditory contrast tuning upon speech intelligibility

(2016) Frontiers in Psychology, 7 (AUG), art. no. 01145, . 

 

DOI: 10.3389/fpsyg.2016.01145

 

a Laboratory of Sensory Neuroscience and Neuroengineering, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States

b Central Institute for the Deaf, Washington University School of Medicine, St. Louis, MO, United States

c Department of Neurosurgery, Massachusetts General Hospital, Boston, United States

d NIH/NINDS/Branch Contractor, Global Solutions Network Inc., Bethesda, United States

 

Abstract

We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast values or all contrast values improved computed intelligibility. Cochlear implant subjects showed significant improvement in noisy speech intelligibility with a contrast shaping procedure. © 2016 Killian, Watkins, Davidson and Barbour.

 

Author Keywords

Auditory cortex;  Cochlear implant;  Human;  Noise reduction;  Primate

 

Document Type: Article

Source: Scopus

 

 

18) Mak, G.Z.a , Lucchetti, A.R.b , Drossos, T.c , Fitzsimmons-Craft, E.E.d , Accurso, E.C.e , Stiles-Shields, C.f , Newman, E.A.g , Skelly, C.L.h 

Pediatric chronic abdominal pain and median arcuate ligament syndrome: A review and psychosocial comparison

(2016) Pediatric Annals, 45 (7), pp. e257-e264. 

 

DOI: 10.3928/00904481-20160613-01

 

a Section of Pediatric Surgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, United States

b Department of Psychiatry and Psychology, Mayo Clinic, United States

c Department of Psychiatry and Behavioral Neuroscience, University of Chicago Medicine and Biological Sciences, United States

d Department of Psychiatry, Washington University School of Medicine, United States

e Department of Psychiatry, University of California, San Francisco, United States

f Department of Preventive Medicine, Center for Behavioral Intervention Technologies, Northwestern University Feinberg School of Medicine, United States

g Section of Pediatric Surgery, Department of Surgery, University of Michigan, United States

h Section of Vascular and Endovascular Surgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, United States

 

Abstract

Chronic abdominal pain (CAP) occurs in children and adolescents with a reported prevalence of 4% to 41% with significant direct and indirect costs to the child, family, and society. Median arcuate ligament syndrome (MALS) is a vascular compression syndrome of the celiac artery that may cause symptoms of epigastric pain and weight loss and is a frequently overlooked cause of CAP in the pediatric population. We have observed that the psychosocial presentation of patients with MALS is notable for various psychiatric comorbidities. In this article, we review MALS as well as our study results of the psychosocial profile of 30 MALS patients. Our data suggest that children and adolescents with MALS have similar psychosocial profiles to children with other gastrointestinal disorders resulting in CAP. The overlap of physical and psychosocial symptoms of patients who have MALS with other CAP disorders leads us to recommend that patients with CAP should be evaluated for MALS. © SLACK Incorporated.

 

Document Type: Review

Source: Scopus

 

 

19) Ray, W.Z.a , Dorward, I.G.a , Masson, R.L.b 

Intervertebral micro access surgery for transforaminal lumbar interbody fusion

(2016) Operative Neurosurgery, 12 (3), pp. 203-213. 

 

DOI: 10.1227/NEU.0000000000001213

 

a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States

b Department of Neurological Surgery, Neurospine Institute, 2706 Rew Circle, Orlando, FL, United States

 

Abstract

Background: Minimally invasive spine surgery (MIS) has undergone tremendous progress in the past 2 decades. The intervertebral micro access surgery (iMAS) technique represents a hybrid of both open and minimally invasive techniques. OBJECTIVE: To describe the surgical technique and operative nuances of the iMAS technique. METHODS: We describe a novel operative approach for the standard transforaminal lumbar interbody fusion with pedicle screw fixation. Described are the preoperative planning, incision and approach, pedicle screw insertion, facetectomy and discectomy, transforaminal interbody placement, and direct decompression. RESULTS: Early experience suggests that iMAS is well suited for the same degenerative conditions currently treated with open or MIS transforaminal lumbar interbody fusion, including grade I spondylolisthesis, unilateral synovial cysts with instability, unilateral disc herniations with instability, and recurrent disc herniations. CONCLUSION: The novel integration of both open and MIS techniques makes iMAS an attractive approach for select degenerative lumbar disease processes. Similar to other MIS procedures, minimal tissue disruption may allow for more rapid patient recovery, reduced blood loss, and reduced length of hospital stay. © 2016 by the Congress of Neurological Surgeons.

 

Author Keywords

iMAS;  Intervertebral micro access surgery;  Lumbar;  Lumbar interbody fusion;  Transforaminal lumbar interbody fusion

 

Document Type: Article

Source: Scopus

 

 

20) Rumalla, K., Karim, A.M., Hullar, T.E.

The effect of hearing aids on postural stability

(2015) Laryngoscope, 125 (3), pp. 720-723. 

 

DOI: 10.1002/lary.24974

 

Department of Otolaryngology-Head and Neck Surgery, Washington University in St. Louis, 660 South Euclid Avenue #8115, St. Louis, MO, United States

 

Abstract

Objectives/Hypothesis: In the United States, falls are the leading cause of accidental deaths in adults aged over 65 years. Epidemiologic studies indicate that there is a correlation between hearing loss and the risk of falling among older people. The vestibular, proprioceptive, and visual systems are known to contribute to postural stability, but the contribution of audition to maintaining balance has not yet been determined. Study Design: Cross-sectional study to measure postural stability in bilateral hearing-aid users aged over 65 years in aided and unaided conditions. Methods: Balance was assessed using the Romberg on foam test and the tandem stance test. Tests were administered in the presence of a point-source broadband white-noise sound (0-4 kHz) source in both unaided and aided conditions in the dark. Subjective measures of balance were made using the Activities-specific Balance Confidence Scale. Results: Performance was significantly better in the aided than the unaided condition (P50.005 for both tests). No statistically significant relationship between improvement in balance, and hearing was identified. Participants did not report that they perceived a difference in balance between the two conditions. Conclusion: These results indicate that hearing aids are a novel treatment modality for imbalance in older adults with hearing loss and suggest that wearing hearing aids may offer a significant public-health benefit for avoiding falls in this population. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

 

Author Keywords

Aid;  Audition;  Auditory;  Balance;  Elderly;  Fall;  Hearing;  Landmark;  Posture;  Romberg;  Stability

 

Document Type: Article

Source: Scopus

 

 

21) Paniello, R.C.

Vocal fold paralysis: Improved adductor recovery by vincristine blockade of posterior cricoarytenoid

(2015) Laryngoscope, 125 (3), pp. 655-660. 

 

DOI: 10.1002/lary.24951

 

Department of Otolaryngology-Head and Neck Surgery, Washington University, St. Louis VA Medical Center, 660 S. Euclid Avenue, St. Louis, MO, United States

 

Abstract

Objectives/Hypothesis: A new treatment for acute unilateral vocal-fold paralysis (UVFP) was proposed in which a drug is injected into the posterior cricoarytenoid muscle (PCA) shortly after nerve injury, before the degree of natural recovery is known, to prevent antagonistic synkinetic reinnervation. This concept was tested in a series of canine experiments using vincristine as the blocking agent. Study Design: Animal experiments. Methods: Laryngeal adductor function was measured at baseline and at 6 months following experimental recurrent laryngeal nerve (RLN) injuries, including complete transection, crush injury, and cautery. In the treatment animals, the PCA was injected with vincristine at the time of RLN injury. Results: Adductor function in the vincristine-treated hemilarynges was significantly improved compared with injurymatched noninjected controls (total n543). Transection/repair controls recovered 56.1% of original adductor strength; vincristine-treated hemilarynges recovered to 73.1% (P50.002). Cautery injuries also improved with vincristine block (60.7% vs. 88.7%; P50.031). Crush injuries recovered well even without vincristine (104.8% vs. 111.2%; P50.35). Conclusion: These findings support a new paradigm of early, preemptive blockade of the antagonist muscle (PCA) to improve ultimate net adductor strength, which could potentially improve functional recovery in many UVFP patients and avoid the need for medialization procedures. Possible clinical aspects of this new approach are discussed. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

 

Author Keywords

Canine;  Injection;  Paralysis;  Synkinesis;  Vocal fold

 

Document Type: Article

 

Source: Scopus