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Neuroscience Publications Archive - December 2016

Weekly Scopus Report

December 21, 2016

December 8, 2016

December 1, 2016

 

December 21, 2016

1) 

Ji, A.a , Godwin, D.a , Rutlin, J.b , Kandala, S.a , Shimony, J.S.b , Mamah, D.a 
Tract-based analysis of white matter integrity in psychotic and nonpsychotic bipolar disorder
(2017) Journal of Affective Disorders, 209, pp. 124-134. 

DOI: 10.1016/j.jad.2016.11.038


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Background At least 50% of individuals with bipolar disorder (BD) present with psychosis during their lifetime. Psychotic symptoms have sometimes been linked to specific genetic and phenotypic markers. This study aims to explore potential differences between bipolar disorder subtypes by measuring white matter integrity of the brain and relationships with clinical measures. Methods Diffusion tensor imaging and clinical measures were acquired from 102 participants, grouped as psychotic bipolar disorder (PBD) (n=48), non-psychotic bipolar disorder (NBD) (n=24), and healthy controls (n=30). We utilized a powerful, automated tool (TRACULA: Tracts Constrained by Underlying Anatomy) to analyze the fractional anisotropy (FA) and mean diffusivity (MD) of 18 white matter tracts. Results Decreased FA in numerous tracts was observed in bipolar disorder groups compared to healthy controls: bilateral cingulum-cingulate gyrus bundles, corticospinal tracts, and superior longitudinal fasciculi as well as the right hemisphere cingulum-angular bundle. Only left uncinate fasciculus FA differed between PBD and NPBD groups. We found no group differences in MD. Positive symptoms correlated with FA in the superior (inversely) and inferior (directly) longitudinal fasciculi. Negative symptoms directly correlated with mean FA of the corticospinal tract and cingulum-angular bundle. Limitations Neurotropic, mood-stabilizing medication prescribed for individuals with BD may interact with measures of white matter integrity in our BD participants. Conclusion Our results indicate decreased white matter coherence in BD. Minimal differences in white matter FA between PBD and NPBD participants suggest related underlying neurobiology. © 2016 Elsevier B.V.


Author Keywords
Bipolar disorder;  DTI;  Psychosis;  TRACULA;  White matter


Document Type: Article
Source: Scopus

 

2) 

Chen, L.-S.a b , Baker, T.c , Brownson, R.C.d e , Carney, R.M.a , Jorenby, D.c , Hartz, S.a , Smock, N.a , Johnson, M.a b , Ziedonis, D.f , Bierut, L.J.a 
Smoking Cessation and Electronic Cigarettes in Community Mental Health Centers: Patient and Provider Perspectives
(2016) Community Mental Health Journal, pp. 1-8. Article in Press. 

DOI: 10.1007/s10597-016-0065-8


a Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave., Box 8134, St. Louis, MO, United States
b BJC Behavioral Health, BJC Healthcare, St. Louis, MO, United States
c Center for Tobacco Research and Intervention, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United States
d Prevention Research Center in St. Louis, Brown School, Washington University in St. Louis, St. Louis, MO, United States
e Division of Public Health Sciences and Alvin J. Siteman Cancer Center, Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
f Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, United States


Abstract
Little is known about patients’ electronic cigarette use, interest in and use of smoking cessation treatments, and providers’ attitude towards such treatment. We assessed patients (N = 231) and providers (45 psychiatrists, 97 case workers) in four Community Mental Health Centers. Interestingly, 50% of smokers reported interest in using electronic cigarettes to quit smoking, and 22% reported current use. While 82% of smokers reported wanting to quit or reduce smoking, 91% of psychiatrists and 84% of case workers reported that patients were not interested in quitting as the lead barrier, limiting the provision of cessation interventions. Providers’ assumption of low patient interest in treatment may account for the low rate of smoking cessation treatment. In contrast, patients report interest and active use of electronic cigarettes to quit smoking. This study highlights the need for interventions targeting different phases of smoking cessation in these patients suffering disproportionately from tobacco dependence. © 2016 Springer Science+Business Media New York


Author Keywords
Electronic cigarettes;  Implementation;  Mental illness;  Smoking cessation


Document Type: Article in Press
Source: Scopus

 

3) 

McCue, L.M.a , Flick, L.H.b , Twyman, K.A.c , Xian, H.d , Conturo, T.E.e 
Prevalence of non-febrile seizures in children with idiopathic autism spectrum disorder and their unaffected siblings: A retrospective cohort study
(2016) BMC Neurology, 16 (1), art. no. 245, . 

DOI: 10.1186/s12883-016-0764-3


a Washington University in St. Louis, School of Medicine, Division of Biostatistics, 660 Euclid Ave., St. Louis, MO, United States
b Saint Louis University, College for Public Health and Social Justice, Epidemiology Department, 3545 Lafayette Ave., St. Louis, MO, United States
c Saint Louis University School of Medicine, Department of Pediatrics, 1465 S Grand Blvd., St Louis, MO, United States
d Saint Louis University, College for Public Health and Social Justice, Department of Biostatistics, 3545 Lafayette Ave., St. Louis, MO, United States
e Washington University School of Medicine, Department of Radiology, 4525 Scott Ave., St Louis, MO, United States


Abstract
Background: Autism spectrum disorder (ASD) is a heterogeneous disorder characterized not only by deficits in communication and social interactions but also a high rate of co-occurring disorders, including metabolic abnormalities, gastrointestinal and sleep disorders, and seizures. Seizures, when present, interfere with cognitive development and are associated with a higher mortality rate in the ASD population. Methods: To determine the relative prevalence of non-febrile seizures in children with idiopathic ASD from multiplex and simplex families compared with the unaffected siblings in a cohort of 610 children with idiopathic ASD and their 160 unaffected siblings, participating in the Autism Genetic Resource Exchange project, the secondary analysis was performed comparing the life-time prevalence of non-febrile seizures. Statistical models to account for non-independence of observations, inherent with the data from multiplex families, were used in assessing potential confounding effects of age, gender, and history of febrile seizures on odds of having non-febrile seizures. Results: The life-time prevalence of non-febrile seizures was 8.2% among children with ASD and 2.5% among their unaffected siblings. In a logistic regression analysis that adjusted for familial clustering, children with ASD had 5.27 (95%CI: 1.51-18.35) times higher odds of having non-febrile seizures compared to their unaffected siblings. In this comparison, age, presence of gastrointestinal dysfunction, and history of febrile seizures were significantly associated with the prevalence of non-febrile seizures. Conclusion: Children with idiopathic ASD are significantly more likely to have non-febrile seizures than their unaffected siblings, suggesting that non-febrile seizures may be ASD-specific. Further studies are needed to determine modifiable risk factors for non-febrile seizures in ASD. © 2016 The Author(s).


Author Keywords
AGRE;  Autism;  Epilepsy;  Familial;  Genetic;  Idiopathic;  Prevalence;  Seizures;  Siblings


Document Type: Article
Source: Scopus

 

4) 

Keefer, K.M., True, H.L.
Prion-Associated Toxicity is Rescued by Elimination of Cotranslational Chaperones
(2016) PLoS Genetics, 12 (11), art. no. e1006431, . 

DOI: 10.1371/journal.pgen.1006431


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


Abstract
The nascent polypeptide-associated complex (NAC) is a highly conserved but poorly characterized triad of proteins that bind near the ribosome exit tunnel. The NAC is the first cotranslational factor to bind to polypeptides and assist with their proper folding. Surprisingly, we found that deletion of NAC subunits in Saccharomyces cerevisiae rescues toxicity associated with the strong [PSI+] prion. This counterintuitive finding can be explained by changes in chaperone balance and distribution whereby the folding of the prion protein is improved and the prion is rendered nontoxic. In particular, the ribosome-associated Hsp70 Ssb is redistributed away from Sup35 prion aggregates to the nascent chains, leading to an array of aggregation phenotypes that can mimic both overexpression and deletion of Ssb. This toxicity rescue demonstrates that chaperone modification can block key steps of the prion life cycle and has exciting implications for potential treatment of many human protein conformational disorders. © 2016 Keefer, True.

 


Document Type: Article
Source: Scopus

 

5) 

Gordon, E.M.a b f , Laumann, T.O.b , Adeyemo, B.b , Gilmore, A.W.c , Nelson, S.M.a f , Dosenbach, N.U.F.b , Petersen, S.E.b c d e 
Individual-specific features of brain systems identified with resting state functional correlations
(2016) NeuroImage, . Article in Press. 

DOI: 10.1016/j.neuroimage.2016.08.032


a VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA
b Departments of Neurology, Washington University School of Medicine, St. Louis, MO, USA
c Departments of Psychological and Brain Sciences, Washington University School of Medicine, St. Louis, MO, USA
d Departments of Radiology, Washington University School of Medicine, St. Louis, MO, USA
e Departments of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA
f Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA


Abstract
Recent work has made important advances in describing the large-scale systems-level organization of human cortex by analyzing functional magnetic resonance imaging (fMRI) data averaged across groups of subjects. However, new findings have emerged suggesting that individuals' cortical systems are topologically complex, containing small but reliable features that cannot be observed in group-averaged datasets, due in part to variability in the position of such features along the cortical sheet. This previous work has reported only specific examples of these individual-specific system features; to date, such features have not been comprehensively described. Here we used fMRI to identify cortical system features in individual subjects within three large cross-subject datasets and one highly sampled within-subject dataset. We observed system features that have not been previously characterized, but 1) were reliably detected across many scanning sessions within a single individual, and 2) could be matched across many individuals. In total, we identified forty-three system features that did not match group-average systems, but that replicated across three independent datasets. We described the size and spatial distribution of each non-group feature. We further observed that some individuals were missing specific system features, suggesting individual differences in the system membership of cortical regions. Finally, we found that individual-specific system features could be used to increase subject-to-subject similarity. Together, this work identifies individual-specific features of human brain systems, thus providing a catalog of previously unobserved brain system features and laying the foundation for detailed examinations of brain connectivity in individuals. © 2016 Elsevier Inc.


Author Keywords
Brain systems;  FMRI;  Functional connectivity;  Individual variability


Document Type: Article in Press
Source: Scopus

 

6) 

Ortega-Rojas, J.a b , Arboleda-Bustos, C.E.a b , Morales, L.a b c , Benítez, B.A.d , Beltrán, D.e , Izquierdo, Á.f , Arboleda, H.a b , Vásquez, R.f 
Study of genetic variants in the BDNF, COMT, DAT1 and SERT genes in Colombian children with attention deficit disorder
(2016) Revista Colombiana de Psiquiatria, . Article in Press. 

DOI: 10.1016/j.rcp.2016.08.006


a Grupo de Neurociencias, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia
b Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia
c Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canadá
d Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, Estados Unidos
e Departamento de Psiquiatría, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia
f Departamento de Pediatría, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia


Abstract
Background: Attention deficit and hyperactive disorder (ADHD) is highly prevalent among children in Bogota City. Both genetic and environmental factors play a very important role in the etiology of ADHD. However, to date few studies have addressed the association of genetic variants and ADHD in the Colombian population. Objectives: To test the genetic association between polymorphisms in the . DAT1, HTTLPR, COMT and . BDNF genes and ADHD in a sample from Bogota City. Methods: We genotyped the most common polymorphisms in . DAT1, SERT, COMT and . BDNF genes associated with ADHD using conventional PCR followed by restriction fragment length polymorphism (RFLP) in 97 trios recruited in a medical center in Bogota. The transmission disequilibrium test (TDT) was used to determine the association between such genetic variants and ADHD. Results: The TDT analysis showed that no individual allele of any variant studied has a preferential transmission. Conclusions: Our results suggest that the etiology of the ADHD may be complex and involves several genetic factors. Further studies in other candidate polymorphisms in a larger sample size will improve our knowledge of the ADHD in Colombian population. © 2016 Asociación Colombiana de Psiquiatría.


Author Keywords
ADHD;  Colombia;  Polymorphisms;  TDT


Document Type: Article in Press
Source: Scopus

 

7) 

Hudson, D.L.a , Kaphingst, K.A.b , Croston, M.A.c , Blanchard, M.S.d , Goodman, M.S.e 
Estimates of mental health problems in a vulnerable population within a primary care setting
(2016) Journal of Health Care for the Poor and Underserved, 27 (1), pp. 308-326. 


a Brown School, Washington University in St. Louis, United States
b Department of Communication and the Huntsman Cancer Institute, University of Utah, United States
c Rollins School of Public Health, Emory University, United States
d Department of Medicine, Washington University School of Medicine, United States
e Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, United States


Abstract
We examined the prevalence of mental disorders in a primary care setting affiliated with a large academic medical center. We also examined whether there were racial differences in mental health disorders. Patients were seeking medical care in an outpatient medical clinic; mental health data were available for them via medical records (n=767). Overall, 45% of patients had a diagnosed mental health problem; the most commonly reported form of mental disorder was depression. African Americans (OR= 1.88; CI: 1.21– 2.91) were more likely than Whites to have a diagnosed mental health problem. These results suggest a strong mental health treatment need among patients seeking primary care in urban settings. The evidence garnered from this study underscores the need to detect and treat mental health problems systematically within outpatient primary care clinics that serve similarly vulnerable populations. © Meharry Medical College.


Author Keywords
Mental health;  Primary care;  Race/ethnicity;  Socioeconomic status


Document Type: Article
Source: Scopus

 

8) 

D'Rozario, M.a , Monk, K.R.a b , Petersen, S.C.c 
Analysis of myelinated axon formation in zebrafish
(2016) Methods in Cell Biology, . Article in Press. 

DOI: 10.1016/bs.mcb.2016.08.001


a Washington University School of Medicine, St. Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
c Kenyon College, Gambier, OH, United States


Abstract
Myelin is a lipid-rich sheath formed by the spiral wrapping of specialized glial cells around axon segments. Myelinating glia allow for rapid transmission of nerve impulses and metabolic support of axons, and the absence of or disruption to myelin results in debilitating motor, cognitive, and emotional deficits in humans. Because myelin is a jawed vertebrate innovation, zebrafish are one of the simplest vertebrate model systems to study the genetics and development of myelinating glia. The morphogenetic cellular movements and genetic program that drive myelination are conserved between zebrafish and mammals, and myelin develops rapidly in zebrafish larvae, within 3-5. days postfertilization. Myelin ultrastructure can be visualized in the zebrafish from larval to adult stages via transmission electron microscopy, and the dynamic development of myelinating glial cells may be observed in vivo via transgenic reporter lines in zebrafish larvae. Zebrafish are amenable to genetic and pharmacological screens, and screens for myelinating glial phenotypes have revealed both genes and drugs that promote myelin development, many of which are conserved in mammalian glia. Recently, zebrafish have been employed as a model to understand the complex dynamics of myelinating glia during development and regeneration. In this chapter, we describe these key methodologies and recent insights into mechanisms that regulate myelination using the zebrafish model. © 2016 Elsevier Inc.


Author Keywords
Myelination;  Oligodendrocyte;  Remyelination;  Schwann cell


Document Type: Article in Press
Source: Scopus

 

December 8, 2016

1) 

Eling, P.a , Finger, S.b , Whitaker, H.c 
On the origins of organology: Franz Joseph Gall and a girl named Bianchi
(2017) Cortex, 86, pp. 123-131. 

DOI: 10.1016/j.cortex.2016.11.010


a Department of Psychology, Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands
b Department of Psychological and Brain Sciences, and Program in History of Medicine, Washington University, St. Louis, MO, United States
c Department of Psychology, Northern Michigan University, Marquette, MI, United States


Abstract
Franz Joseph Gall (1758–1828) introduced a new theory of mind and brain at the end of the eighteenth century, which he referred to as organology, dealing with mental functions and their cortical localizations. Gall wrote that observations regarding the verbal learning capacities of his schoolmates brought about his new way of thinking. This widely accepted view, however, requires qualification. Although Gall's experiences and observations as a schoolboy were relevant, especially for his craniology, these childhood memories might have been recalled and reinterpreted after he had started to think about the faculties of mind—specifically after he had met Bianchi, a 5-year-old girl with a special talent for music. © 2016 Elsevier Ltd


Author Keywords
Craniology;  Franz Joseph Gall;  Localization of function;  Music;  Organology;  Phrenology


Document Type: Article
Source: Scopus

 

2) 

Natelson Love, M.a b c , Clark, D.G.a b c d , Cochran, J.N.b e , Den Beste, K.A.b e , Geldmacher, D.S.a b f , Benzinger, T.L.g h , Gordon, B.A.g h , Morris, J.C.g , Bateman, R.J.g , Roberson, E.D.a b e f 
Clinical, imaging, pathological, and biochemical characterization of a novel presenilin 1 mutation (N135Y) causing Alzheimer's disease
(2017) Neurobiology of Aging, 49, p. 216. 

DOI: 10.1016/j.neurobiolaging.2016.09.020


a Alzheimer's Disease Center, University of Alabama at Birmingham, Birmingham, AL, United States
b Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States
c Department of Neurology, Birmingham VA Medical Center, Birmingham, AL, United States
d Department of Neurology, Ralph H. Johnson VA Medical Center, Medical University of South Carolina, Charleston, SC, United States
e Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, United States
f McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, United States
g Dominantly Inherited Alzheimer's Network, Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
h Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
We present 2 cases of early-onset Alzheimer's disease due to a novel N135Y mutation in PSEN1. The proband presented with memory and other cognitive symptoms at age 32. Detailed clinical characterization revealed initial deficits in memory with associated dysarthria, progressing to involve executive dysfunction, spastic gait, and episodic confusion with polyspike discharges on long-term electroencephalography. Amyloid- and FDG-PET scans showed typical results of Alzheimer's disease. By history, the proband's father had developed cognitive symptoms at age 42 and died at age 48. Neuropathological evaluation confirmed Alzheimer's disease, with moderate to severe amyloid angiopathy. Skeletal muscle showed type 2 fiber–predominant atrophy with pale central clearing. Genetic testing of the proband revealed an N135Y missense mutation in PSEN1. This mutation was predicted to be pathogenic by in silico analysis. Biochemical analysis confirmed that the mutation caused an increased Aβ42/Aβ40 ratio, consistent with other PSEN1 mutations and with a loss of presenilin function. © 2016


Author Keywords
Alzheimer's disease;  Elecrtoencephalography;  PET scan;  Presenilin 1


Document Type: Article
Source: Scopus

 

3) 

Salazar, D.H., Chalmers, P.N., Mackinnon, S.E., Keener, J.D.
Reverse shoulder arthroplasty after radial-to-axillary nerve transfer for axillary nerve palsy with concomitant irreparable rotator cuff tear
(2017) Journal of Shoulder and Elbow Surgery, 26 (1), pp. e23-e28. 

DOI: 10.1016/j.jse.2016.09.025


Department of Orthopaedic Surgery, Washington University Medical Center, St. Louis, MO, United States

 


Author Keywords
Axillary nerve palsy;  axillary-to-radial nerve transfer;  deltoid dysfunction;  irreparable rotator cuff tear;  reverse shoulder arthroplasty;  shoulder pseudoparalysis


Document Type: Article
Source: Scopus

 

4) 

van den Berk-Clark, C.a , Patterson Silver Wolf, D.b 
Mental Health Help Seeking Among Traumatized Individuals: A Systematic Review of Studies Assessing the Role of Substance Use and Abuse
(2017) Trauma, Violence, and Abuse, 18 (1), pp. 106-116. 

DOI: 10.1177/1524838015596344


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Brown School of Social Work, Washington University, St. Louis, MO, United States


Abstract
Objective: Prior research has suggested that competing neurobehavioral decision-making processes might affect health outcomes among traumatized populations. Regulatory imbalances to impulsive and executive decision systems are affected by high levels of stress, including stress resulting from traumatic events. Such regulatory imbalances have been associated with addictive behaviors. However, it is not well known whether addictive behavior increases or decreases the likelihood of utilization of behavioral health services among traumatized populations. The aim of this study is to systematically review mental health utilization studies targeting traumatized populations to determine the direction of association between substance use and behavioral health utilization. Method: Databases of literature were searched in a systematic manner, and 37 relevant studies were recovered and analyzed. Findings: Of the 37 relevant studies that included addictive behaviors as a predictor of utilization, 16 showed a positive significant relationship and 6 showed a negative significant relationship. Studies showing a negative significant relationship used younger samples with more recent trauma exposure. Conclusion: Studies have shown that for the most part, substance abuse increases the likelihood of utilization, except among younger populations with more recent trauma. Longitudinal studies that access how utilization evolves over time among traumatized populations and interacts with posttraumatic stress disorder (PTSD) and substance abuse severity are necessary to better understand how decision-making processes of traumatized individuals may increase the likelihood of chronic PTSD. © 2015, © The Author(s) 2015.


Author Keywords
mental health utilization;  substance use;  systematic review;  trauma


Document Type: Article
Source: Scopus

 

5) 

Baugh, J.
Meaning-Less Differences: Exposing Fallacies and Flaws in “The Word Gap” Hypothesis That Conceal a Dangerous “Language Trap” for Low-Income American Families and Their Children
(2016) International Multilingual Research Journal, pp. 1-13. Article in Press. 

DOI: 10.1080/19313152.2016.1258189


Psychological and Brain Sciences, Anthropology, Linguistics, and African and African American Studies Washington University in St. Louis


Abstract
The present article compares and contrasts linguistic findings from longitudinal studies of low-income Americans derived from evidence of recorded family speech interactions. Hart and Risley (1995) employed research assistants who spent 1 hour per month observing language usage among families from different socioeconomic backgrounds in their homes for 2.5 years. Baugh (1983) spent 40 hours per week during seven consecutive summers between 1969 and 1976 as a participant observer in a low-income African American community, conducting tape recorded interviews with African American families in various social circumstances during the final 4 years, which always included recorded interviews within each family home. Comparison of the linguistic results derived from the alternative data collection procedures allow for a reinterpretation of Hart and Risley’s (1995, 2003) conclusions, casting doubt on their findings as well as their speculations about future linguistic prospects for Americans from diverse racial and socioeconomic backgrounds due to false positive interpretations of their results that wrongly conclude deceptively enticing causalities. Regrettably, the alleged “word gap” is another incarnation of a deficit language hypothesis that is fundamentally flawed and woefully uninformed by decades of extensive linguistic research that has been conducted by many different linguists in various American inner-city communities since 1968. © 2016 Taylor & Francis


Author Keywords
educational disparities;  Linguistic diversity;  phonological and grammatical dialect differences


Document Type: Article in Press
Source: Scopus

 

6) 

Khandekar, A.a , Springer, S.a , Wang, W.a , Hicks, S.a , Weinheimer, C.a , Diaz-Trelles, R.c , Nerbonne, J.M.ab , Rentschler, S.a b 
Notch-Mediated Epigenetic Regulation of Voltage-Gated Potassium Currents
(2016) Circulation Research, 119 (12), pp. 1324-1338. 

DOI: 10.1161/CIRCRESAHA.116.309877


a Cardiovascular Division, Department of Medicine, Washington University, School of Medicine, 309 McDonnell Science Bldg, 660 S Euclid Ave, St Louis, MO, United States
b Department of Developmental Biology, Washington University, School of Medicine, St Louis, MO, United States
c Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA, United States


Abstract
Rationale: Ventricular arrhythmias often arise from the Purkinje-myocyte junction and are a leading cause of sudden cardiac death. Notch activation reprograms cardiac myocytes to an induced Purkinje-like state characterized by prolonged action potential duration and expression of Purkinje-enriched genes. Objective: To understand the mechanism by which canonical Notch signaling causes action potential prolongation. Methods and Results: We find that endogenous Purkinje cells have reduced peak K + current, I to, and I K,slow when compared with ventricular myocytes. Consistent with partial reprogramming toward a Purkinje-like phenotype, Notch activation decreases peak outward K + current density, as well as the outward K + current components I to,f and I K, slow. Gene expression studies in Notch-activated ventricles demonstrate upregulation of Purkinje-enriched genes Contactin-2 and Scn5a and downregulation of K + channel subunit genes that contribute to I to,f and I K,slow. In contrast, inactivation of Notch signaling results in increased cell size commensurate with increased K + current amplitudes and mimics physiological hypertrophy. Notch-induced changes in K + current density are regulated at least in part via transcriptional changes. Chromatin immunoprecipitation demonstrates dynamic RBP-J (recombination signal binding protein for immunoglobulin kappa J region) binding and loss of active histone marks on K + channel subunit promoters with Notch activation, and similar transcriptional and epigenetic changes occur in a heart failure model. Interestingly, there is a differential response in Notch target gene expression and cellular electrophysiology in left versus right ventricular cardiac myocytes. Conclusions: In summary, these findings demonstrate a novel mechanism for regulation of voltage-gated potassium currents in the setting of cardiac pathology and may provide a novel target for arrhythmia drug design. © 2016 American Heart Association, Inc.


Author Keywords
action potential;  Brugada syndrome;  cardiomyopathies;  cellular reprogramming;  electrophysiology;  Notch receptors Purkinje cells


Document Type: Article
Source: Scopus

 

7) 

Tharp, M.a , Holtzman, N.S.a , Eadeh, F.R.b 
Mind Perception and Individual Differences: A Replication and Extension
(2016) Basic and Applied Social Psychology, pp. 1-6. Article in Press. 

DOI: 10.1080/01973533.2016.1256287


a Georgia Southern University
b Washington University in St. Louis


Abstract
Mind perception involves attributing higher functional abilities to others (e.g., saying a dog feels pain). The relationships between mind perception and psychopathology—autism, psychopathy, and schizotypy—have been revealed by K. Gray, Jenkins, Heberlein, and Wegner (2011); however, mind perception has yet to be correlated with personality. Participants (N = 180) completed measures of personality, psychopathology, and mind perception. The psychopathology results were consistent with Gray et al. (2011). The Big Five captured mind perception virtually as much as the three psychopathologies captured mind perception. Mind perception is not solely relevant to psychopathology; it is also relevant to everyday personality. © 2016 Taylor & Francis

 


Document Type: Article in Press
Source: Scopus

 

8) 

English, T.a , Lee, I.A.b , John, O.P.c , Gross, J.J.b 
Emotion regulation strategy selection in daily life: The role of social context and goals
(2016) Motivation and Emotion, pp. 1-13. Article in Press. 

DOI: 10.1007/s11031-016-9597-z


a Department of Psychological and Brain Science, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychology, Stanford University, Stanford, CA, United States
c Department of Psychology, Institute of Personality and Social Research, University of California, Berkeley, Berkeley, CA, United States


Abstract
Recent studies have begun to document the diversity of ways people regulate their emotions. However, one unanswered question is why people regulate their emotions as they do in everyday life. In the present research, we examined how social context and goals influence strategy selection in daily high points and low points. As expected, suppression was particularly tied to social features of context: it was used more when others were present, especially non-close partners, and when people had instrumental goals, especially more interpersonal ones (e.g., avoid conflict). Distraction and reappraisal were used more when regulating for hedonic reasons (e.g., to feel better), but these strategies were also linked to certain instrumental goals (e.g., getting work done). When contra-hedonic regulation occurred, it primarily took the form of dampening positive emotion during high points. Suppression was more likely to be used for contra-hedonic regulation, whereas reappraisal and distraction were used more for pro-hedonic regulation. Overall, these findings highlight the social nature of emotion regulation and underscore the importance of examining regulation in both positive and negative contexts. © 2016 Springer Science+Business Media New York


Author Keywords
Emotion;  Emotion regulation;  Goals;  Motivation;  Relationships


Document Type: Article in Press
Source: Scopus

 

9) 

Chapuis, J.a , Flaig, A.a , Grenier-Boley, B.a , Eysert, F.a , Pottiez, V.b c , Deloison, G.b c , Vandeputte, A.b c , Ayral, A.-M.a , Mendes, T.a , Desai, S.a , Goate, A.M.d e , Kauwe, J.S.K.f , Leroux, F.c , Herledan, A.c , Demiautte, F.a , Bauer, C.g , Checler, F.g , Petersen, R.C.h , Blennow, K.i , Zetterberg, H.i j , Minthon, L.k , van Deerlin, V.M.l , Lee, V.M.-Y.l , Shaw, L.M.l , Trojanowski, J.Q.l , Albert, M.m , Moghekar, A.m , O’Brien, R.n , Peskind, E.R.o , Malmanche, N.a , Schellenberg, G.D.p , Dourlen, P.a , Song, O.-R.b , Cruchaga, C.d e , Amouyel, P.a , Deprez, B.c , Brodin, P.b , Lambert, J.-C.a , Adgc, Alzheimer’S Disease Neuroimaging Initiativeq 
Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism
(2016) Acta Neuropathologica, pp. 1-12. Article in Press. 

DOI: 10.1007/s00401-016-1652-z


a Laboratoire d’Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, Lille cedex, France
b Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, Lille, France
c Univ. Lille, INSERM, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, Lille, France
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
f Departments of Biology and Neuroscience, Brigham Young University, Provo, United States
g Laboratoire d’Excellence DistALZ, Université Côte d’Azur, INSERM, CNRS, IPMC, France, 660 route des Lucioles, Sophia-Antipolis, Valbonne, France
h Department of Neurology, Mayo Clinic, Rochester, MN, United States
i Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren’s University Hospital, Mölndal, Gothenburg, Sweden
j Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom
k Clinical Memory Research Unit, Dept of Clinical Sciences, Lund University, Lund, Sweden
l Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
m Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
n Department of Neurology, Duke Medical Center, Box 2900, Durham, NC, United States
o Departments of Psychiatry and Behavioral Sciences, Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, University of Washington School of Medicine, Seattle, United States
p Stellar-Chance Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States


Abstract
Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production. © 2016 The Author(s)

 


Document Type: Article in Press
Source: Scopus

 

10) 

van Engen, K.J.a b c , Xie, Z.a , Chandrasekaran, B.a 
Audiovisual sentence recognition not predicted by susceptibility to the McGurk effect
(2016) Attention, Perception, and Psychophysics, pp. 1-8. Article in Press. 

DOI: 10.3758/s13414-016-1238-9


a Department of Communication Sciences and Disorders, The University of Texas at Austin, Austin, TX, United States
b Department of Linguistics, The University of Texas at Austin, Austin, TX, United States
c Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States


Abstract
In noisy situations, visual information plays a critical role in the success of speech communication: listeners are better able to understand speech when they can see the speaker. Visual influence on auditory speech perception is also observed in the McGurk effect, in which discrepant visual information alters listeners’ auditory perception of a spoken syllable. When hearing /ba/ while seeing a person saying /ga/, for example, listeners may report hearing /da/. Because these two phenomena have been assumed to arise from a common integration mechanism, the McGurk effect has often been used as a measure of audiovisual integration in speech perception. In this study, we test whether this assumed relationship exists within individual listeners. We measured participants’ susceptibility to the McGurk illusion as well as their ability to identify sentences in noise across a range of signal-to-noise ratios in audio-only and audiovisual modalities. Our results do not show a relationship between listeners’ McGurk susceptibility and their ability to use visual cues to understand spoken sentences in noise, suggesting that McGurk susceptibility may not be a valid measure of audiovisual integration in everyday speech processing. © 2016 The Psychonomic Society, Inc.


Author Keywords
Audiovisual speech perception;  McGurk effect;  Speech perception in noise


Document Type: Article in Press
Source: Scopus

 

11) 

Liao, F., Yoon, H., Kim, J.
Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease
(2016) Current Opinion in Lipidology, . Article in Press. 

DOI: 10.1097/MOL.0000000000000383


aDepartment of Neurology, Washington University School of Medicine, St. Louis, Missouri bNeurobiology of Disease Graduate Program, Mayo Graduate School cDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA


Abstract
PURPOSE OF REVIEW: APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. RECENT FINDINGS: ApoE isoforms have differential effects on amyloid β metabolism. Recent studies demonstrated that ApoE-interacting proteins, such as ATP-binding cassette A1 (ABCA1) and LDL receptor, may be promising therapeutic targets for Alzheimer's disease treatment. Activation of liver X receptor and retinoid X receptor pathway induces ABCA1 and other genes, leading to amyloid β clearance. Inhibition of the negative regulators of ABCA1, such as microRNA-33, also induces ABCA1 and decreases the levels of ApoE and amyloid β. In addition, genetic inactivation of an E3 ubiquitin ligase, myosin regulatory light chain interacting protein, increases LDL receptor levels and inhibits amyloid accumulation. Although amyloid β-dependent pathways have been extensively investigated, there have been several recent studies linking ApoE with vascular function, neuroinflammation, metabolism, synaptic plasticity, and transcriptional regulation. For example, ApoE was identified as a ligand for a microglial receptor, TREM2, and studies suggested that ApoE may affect the TREM2-mediated microglial phagocytosis. SUMMARY: Emerging data suggest that ApoE affects several amyloid β-independent pathways. These underexplored pathways may provide new insights into Alzheimer's disease pathogenesis. However, it will be important to determine to what extent each mechanism contributes to the pathogenesis of Alzheimer's disease.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

 


Document Type: Article in Press
Source: Scopus

 

12) 

Esparza, T.J.a , Wildburger, N.C.a , Jiang, H.a , Gangolli, M.b , Cairns, N.J.a c d , Bateman, R.J.a c d , Brody, D.L.a b d 
Soluble amyloid-beta aggregates from human Alzheimer's disease brains
(2016) Scientific Reports, 6, art. no. 38187, . 

DOI: 10.1038/srep38187


a Department of Neurology, Washington University, 660 South Euclid Avenue, St. Louis, MO, United States
b Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
c Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO, United States
d Hope Center for Neurological Disorders, Washington University, St. Louis, MO, United States


Abstract
Soluble amyloid-beta (Aβ) aggregates likely contribute substantially to the dementia that characterizes Alzheimer's disease. However, despite intensive study of in vitro preparations and animal models, little is known about the characteristics of soluble Aβ aggregates in the human Alzheimer's disease brain. Here we present a new method for extracting soluble Aβ aggregates from human brains, separating them from insoluble aggregates and Aβ monomers using differential ultracentrifugation, and purifying them >6000 fold by dual antibody immunoprecipitation. The method resulted in <40% loss of starting material, no detectible ex vivo aggregation of monomeric Aβ, and no apparent ex vivo alterations in soluble aggregate sizes. By immunoelectron microscopy, soluble Aβ aggregates typically appear as clusters of 10-20 nanometer diameter ovoid structures with 2-3 amino-terminal Aβ antibody binding sites, distinct from previously characterized structures. This approach may facilitate investigation into the characteristics of native soluble Aβ aggregates, and deepen our understanding of Alzheimer's dementia. © The Author(s) 2016.

 


Document Type: Article
Source: Scopus

 

13) 

Cabrera, O.H.a b , O’Connor, S.D.c , Swiney, B.S.b , Salinas-Contreras, P.b , Manzella, F.M.a b , Taylor, G.T.a , Noguchi, K.K.b 
Caffeine combined with sedative/anesthetic drugs triggers widespread neuroapoptosis in a mouse model of prematurity
(2016) Journal of Maternal-Fetal and Neonatal Medicine, pp. 1-8. Article in Press. 

DOI: 10.1080/14767058.2016.1261400


a Department of Psychological Sciences, University of Missouri – St. Louis, St. Louis, MO, USA
b Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
c Edward Mallinckrodt Department of Pediatrics, Division of Newborn Medicine, Washington University in St. Louis School of Medicine and St. Louis Children’s Hospital, St. Louis, MO, USA


Abstract
Objectives: Caffeine (CAF) and sedative/anesthetic drugs (SADs) are often coadministered to premature infants in the neonatal intensive care unit (NICU). While SAD neurotoxicity in the developing brain is well established, it is not fully clear whether CAF interacts with SADs and whether this interaction is detrimental. Using a mouse model of prematurity, we hypothesized that CAF would increase apoptotic neurotoxicity when coadministered with SADs. Methods: Postnatal day 3 mice were treated with vehicle or 80 mg/kg CAF prior to challenge with 6 mg/kg midazolam, 40 mg/kg ketamine, or 40 μg/kg fentanyl. Six hours later, pups were sacrificed for activated caspase 3 (AC3) immunohistochemistry, and number of AC3 positive cells per mm3 throughout neocortex, hippocampus, caudate, thalamus, and colliculi was analyzed. Results: CAF caused a statistically significant increase in AC3 positive cells when coadministered with midazolam (p = 0.002), ketamine (p = 0.014), or fentanyl (p &lt; 0.001). Our composite dataset suggests that the addition of CAF to these SADs has a supra-additive effect, causing more neurotoxicity than expected. Conclusions: CAF may augment the neurotoxic action of SADs indicated for neonatal sedation/anesthesia in the NICU by triggering widespread apoptosis in the developing brains of premature infants. © 2016 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
apoptosis;  Caffeine;  fentanyl;  ketamine;  midazolam;  premature infant


Document Type: Article in Press
Source: Scopus

 

14) 

Davies, A.a , Brown, G.a , Vigo, M.a , Harper, S.a , Horseman, L.b , Splendiani, B.c , Hill, E.d , Jay, C.a 
Exploring the relationship between eye movements and electrocardiogram interpretation accuracy
(2016) Scientific Reports, 6, art. no. 38227, . 

DOI: 10.1038/srep38227


a Department of Computer Science, University of Manchester, Manchester, United Kingdom
b Department of Medicine, University of Sheffield, Sheffield, United Kingdom
c Department of Library and Information Science, University of Barcelona, Barcelona, Spain
d Department of Surgery, Washington University, Saint Louis, United States


Abstract
Interpretation of electrocardiograms (ECGs) is a complex task involving visual inspection. This paper aims to improve understanding of how practitioners perceive ECGs, and determine whether visual behaviour can indicate differences in interpretation accuracy. A group of healthcare practitioners (n = 31) who interpret ECGs as part of their clinical role were shown 11 commonly encountered ECGs on a computer screen. The participants' eye movement data were recorded as they viewed the ECGs and attempted interpretation. The Jensen-Shannon distance was computed for the distance between two Markov chains, constructed from the transition matrices (visual shifts from and to ECG leads) of the correct and incorrect interpretation groups for each ECG. A permutation test was then used to compare this distance against 10,000 randomly shuffled groups made up of the same participants. The results demonstrated a statistically significant (α0.05) result in 5 of the 11 stimuli demonstrating that the gaze shift between the ECG leads is different between the groups making correct and incorrect interpretations and therefore a factor in interpretation accuracy. The results shed further light on the relationship between visual behaviour and ECG interpretation accuracy, providing information that can be used to improve both human and automated interpretation approaches. © The Author(s) 2016.

 


Document Type: Article
Source: Scopus

 

15) 

Avila, J.D.a b , Lacomis, D.b , Lam, E.M.b 
Neuralgic Amyotrophy Associated with Hepatitis e Virus Infection: First Case in the United States
(2016) Journal of Clinical Neuromuscular Disease, 18 (2), pp. 96-100. 

DOI: 10.1097/CND.0000000000000137


a Neuromuscular Division, Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 South Euclid Avenue, St. Louis, MO, United States
b Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States


Abstract
Hepatitis E is an emerging viral infection in developed countries. It can present with multiple extra-hepatic manifestations, including neuralgic amyotrophy. We report a 52-year-old man who presented with neck and shoulder pain followed by orthopnea and left arm weakness. Electrodiagnostic testing showed left phrenic neuropathy and denervation in bilateral C5 and C6 myotomes. He also had elevated liver enzymes, which led to the diagnosis of acute hepatitis E. This is the first case of neuralgic amyotrophy associated with hepatitis E in the United States. Hepatitis E should be considered in patients with neuralgic amyotrophy, particularly men with bilateral symptoms, and if there is unexplained elevation of transaminases. The role of antiviral therapy remains unclear. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Author Keywords
extra-hepatic manifestations;  hepatitis E;  neuralgic amyotrophy;  Parsonage-Turner syndrome;  phrenic neuropathy


Document Type: Review
Source: Scopus

 

16) 

Siegel, J.S.a , Snyder, A.Z.a b , Ramsey, L.a , Shulman, G.L.a , Corbetta, M.a b c 
The effects of hemodynamic lag on functional connectivity and behavior after stroke
(2016) Journal of Cerebral Blood Flow and Metabolism, 36 (12), pp. 2162-2176. 

DOI: 10.1177/0271678X15614846


a Departments of Neurology, Washington University, School of Medicine, 4525 Scott Ave, St. Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
c Anatomy and Neurobiology, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
Stroke disrupts the brain's vascular supply, not only within but also outside areas of infarction. We investigated temporal delays (lag) in resting state functional magnetic resonance imaging signals in 130 stroke patients scanned two weeks, three months and 12 months post stroke onset. Thirty controls were scanned twice at an interval of three months. Hemodynamic lag was determined using cross-correlation with the global gray matter signal. Behavioral performance in multiple domains was assessed in all patients. Regional cerebral blood flow and carotid patency were assessed in subsets of the cohort using arterial spin labeling and carotid Doppler ultrasonography. Significant hemodynamic lag was observed in 30% of stroke patients sub-acutely. Approximately 10% of patients showed lag at one-year post-stroke. Hemodynamic lag corresponded to gross aberrancy in functional connectivity measures, performance deficits in multiple domains and local and global perfusion deficits. Correcting for lag partially normalized abnormalities in measured functional connectivity. Yet post-stroke FC-behavior relationships in the motor and attention systems persisted even after hemodynamic delays were corrected. Resting state fMRI can reliably identify areas of hemodynamic delay following stroke. Our data reveal that hemodynamic delay is common sub-acutely, alters functional connectivity, and may be of clinical importance. © The Author(s) 2015.


Author Keywords
Acute stroke;  brain ischemia;  cerebral blood flow;  cerebral hemodynamics;  cognitive impairment;  functional MRI


Document Type: Article
Source: Scopus

 

17) 

Tye-Murray, N.
Better hearing? Game on!
(2016) ASHA Leader, 21 (12), pp. 18-19. 

DOI: 10.1044/leader.AEA.21122016.18


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

 

 


Document Type: Note
Source: Scopus

 

18) 

Wahlstrom-Helgren, S., Klyachko, V.A.
Dynamic balance of excitation and inhibition rapidly modulates spike probability and precision in feed-forward hippocampal circuits
(2016) Journal of Neurophysiology, 116 (6), pp. 2564-2575. 

DOI: 10.1152/jn.00413.2016


Departments of Cell Biology & Physiology and Biomedical Engineering, Center for the Investigation of Membrane Excitable Diseases, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Feed-forward inhibitory (FFI) circuits are important for many information-processing functions. FFI circuit operations critically depend on the balance and timing between the excitatory and inhibitory components, which undergo rapid dynamic changes during neural activity due to short-term plasticity (STP) of both components. How dynamic changes in excitation/inhibition (E/I) balance during spike trains influence FFI circuit operations remains poorly understood. In the current study we examined the role of STP in the FFI circuit functions in the mouse hippocampus. Using a coincidence detection paradigm with simultaneous activation of two Schaffer collateral inputs, we found that the spiking probability in the target CA1 neuron was increased while spike precision concomitantly decreased during high-frequency bursts compared with a single spike. Blocking inhibitory synaptic transmission revealed that dynamics of inhibition predominately modulates the spike precision but not the changes in spiking probability, whereas the latter is modulated by the dynamics of excitation. Further analyses combining whole cell recordings and simulations of the FFI circuit suggested that dynamics of the inhibitory circuit component may influence spiking behavior during bursts by broadening the width of excitatory postsynaptic responses and that the strength of this modulation depends on the basal E/I ratio. We verified these predictions using a mouse model of fragile X syndrome, which has an elevated E/I ratio, and found a strongly reduced modulation of postsynaptic response width during bursts. Our results suggest that changes in the dynamics of excitatory and inhibitory circuit components due to STP play important yet distinct roles in modulating the properties of FFI circuits. © 2016 the American Physiological Society.


Author Keywords
Feed-forward inhibition;  Short-term plasticity;  Synaptic dynamics


Document Type: Article
Source: Scopus

 

19) 

Goodwill, V.S.a , Terrill, C.a , Hopewood, I.a , Loewy, A.D.b , Knuepfer, M.M.a 
CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline in awake rats
(2016) Autonomic Neuroscience: Basic and Clinical, . Article in Press. 

DOI: 10.1016/j.autneu.2016.09.015


a Department of Pharmacology and Physiology, St. Louis University School of Medicine, St. Louis, MO 63104, USA
b Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA


Abstract
In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500. mOsm) into the left renal pelvis of conscious rats for two 2. hours while recording arterial pressure and heart rate. Subsequently, brain tissue was analyzed for immunohistochemical detection of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons were identified in numerous sites in the forebrain and brainstem. These areas included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). The most effective stimulus was 500. mOsm NaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1. μM) or amiloride (10. μM) into the renal pelvis concomitantly with hypertonic saline. In anesthetized rats, infusion of hypertonic saline but not isotonic saline into the renal pelvis elevated ARN activity and this increase was attenuated by simultaneous infusion of benzamil or amiloride. We propose that renal pelvic epithelial sodium channels (ENaCs) play a role in activation of ARN and, via central visceral afferent circuits, this system modulates fluid volume and peripheral blood pressure. These pathways may contribute to the development of hypertension. © 2016 Elsevier B.V.


Author Keywords
Arterial pressure regulation;  c-fos activation;  CNS projections;  Epithelial sodium channels (ENaCs);  Fluid volume regulation;  Hypertonic saline;  Renal afferent nerves


Document Type: Article in Press
Source: Scopus

 

20) 

Walkley, S.U.a , Davidson, C.D.a , Jacoby, J.b , Marella, P.D.c , Ottinger, E.A.d , Austin, C.P.e , Porter, F.D.f , Vite, C.H.g , Ory, D.S.h 
Fostering collaborative research for rare genetic disease: The example of niemann-pick type C disease
(2016) Orphanet Journal of Rare Diseases, 11 (1), art. no. 161, . 

DOI: 10.1186/s13023-016-0540-x


a Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY, United States
b Hide and Seek Foundation for Lysosomal Disease Research, 6475 East Pacific Coast Highway, Long Beach, CA, United States
c Dana's Angels Research Trust, 15 East Putnam Ave., #117, Greenwich, CT, United States
d Division of PreClinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, United States
e National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, United States
f Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, 10CRC, 10 Center Dr, Bethesda, MD, United States
g Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, United States
h Diabetic Cardiovascular Disease Center, Washington University School of Medicine, 660 S. Euclid Ave, Box 8086, St. Louis, MO, United States


Abstract
Rare disease represents one of the most significant issues facing the medical community and health care providers worldwide, yet the majority of these disorders never emerge from their obscurity, drawing little attention from the medical community or the pharmaceutical industry. The challenge therefore is how best to mobilize rare disease stakeholders to enhance basic, translational and clinical research to advance understanding of pathogenesis and accelerate therapy development. Here we describe a rare, fatal brain disorder known as Niemann-Pick type C (NPC) and an innovative research collaborative known as Support of Accelerated Research for NPC (SOAR-NPC) which illustrates one pathway through which knowledge of a rare disease and its possible treatments are being successfully advanced. Use of the "SOAR" mechanism, we believe, offers a blueprint for similar advancement for many other rare disorders. © 2016 The Author(s).


Author Keywords
Collaborative science;  Cyclodextrin;  Drug pipeline;  Lysosomal disease;  Miglustat;  Niemann-Pick C;  Patient advocacy;  Rare disease;  Therapy development;  Translational medicine


Document Type: Article
Source: Scopus

 

21) 

Sommerville, R.B.a , Vincenti, M.G.b , Winborn, K.b , Casey, A.b , Stitziel, N.O.b , Connolly, A.M.a , Mann, D.L.b 
Diagnosis and management of adult hereditary cardio-neuromuscular disorders: A model for the multidisciplinary care of complex genetic disorders
(2016) Trends in Cardiovascular Medicine, . Article in Press. 

DOI: 10.1016/j.tcm.2016.06.005


a Department of Neurology, Washington University School of Medicine, St. Louis, MO
b Center for Cardiovascular Research, Cardiovascular Division, Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave., Campus PO Box 8066, St. Louis, MO 63110-1093


Abstract
Genetic disorders that disrupt the structure and function of the cardiovascular system and the peripheral nervous system are common enough to be encountered in routine cardiovascular practice. Although often these patients are diagnosed in childhood and come to the cardiologist fully characterized, some patients with hereditary neuromuscular disease may not manifest until adulthood and will present initially to the adult cardiologist for an evaluation of an abnormal ECG, unexplained syncope, LV hypertrophy, and or a dilated cardiomyopathy of unknown cause. Cardiologists are often ill-equipped to manage these patients due to lack of training and exposure as well as the complete absence of practice guidelines to aid in the diagnosis and management of these disorders. Here, we review three key neuromuscular diseases that affect the cardiovascular system in adults (myotonic dystrophy type 1, Friedreich ataxia, and Emery-Dreifuss muscular dystrophy), with an emphasis on their clinical presentation, genetic and molecular pathogenesis, and recent important research on medical and interventional treatments. We also advocate the development of interdisciplinary cardio-neuromuscular clinics to optimize the care for these patients. © 2016 Elsevier Inc.


Author Keywords
Heart disease;  Heart failure;  Multidisciplinary care;  Neuromuscular disease


Document Type: Article in Press
Source: Scopus

 

22) 

Mraz, K.M.a , Amadio, G.a , Diener, P.b , Eisenberg, G.a , Engsberg, J.R.a 
Improving upper extremity motor skills in girls with rett syndrome using virtual reality
(2016) Journal of Intellectual Disability - Diagnosis and Treatment, 4 (3), pp. 142-151. 

DOI: 10.6000/2292-2598.2016.04.03.1


a Washington University in St. Louis-School of Medicine, Program in Occupational Therapy, 4444 Forest Park Ave, Saint Louis, MO, United States
b Georgetown University-School of Medicine, Department of Neuroscience, 3970 Reservoir Rd NW, Washington, DC, United States


Abstract
Introduction: Rett Syndrome is a genetic disorder that limits a girl's ability to use her upper extremities for daily activities, such as dressing and playing. One possible intervention to improve upper extremity function in this population is virtual reality, which can be used to increase activity demands during therapy sessions. Objectives: To determine the feasibility of using internet-based virtual reality intervention for Rett Syndrome (RTT-IVR), to decrease hand wringing/mouthing and increase hand and arm movements away from the midline by identifying attributes and limitations to the proposed intervention. Materials and Methods: Using FAAST Software and Microsoft Kinect sensor, RTT-IVR was trialed with 6 girls with RTT. Upper extremity movements were used to play free Internet games as means of increasing repetitions and purposeful arm movements. Data regarding attributes and limitations of the RTT-IVR intervention were collected via observation and post-session parent interviews. Results: Interviews and observation revealed successful game play when games were motivating, clearly established cause and effect, and matched level of cognitive ability of the participant. Limitations include technological glitches regarding Kinect sensor sensitivity and identifying appropriate games for each participant's interests and abilities. Conclusion: Internet based virtual reality interventions for girls with RTT should be highly individualized to increase motivation and success of intervention. © 2016 Lifescience Global.


Author Keywords
Internet-based virtual reality;  Microsoft kinect;  Qualitative analysis;  Rett syndrome;  Upper extremity movements


Document Type: Article
Source: Scopus

 

23) 

Engsberg, J.R.
Editorial: The versatility of using free internet videogames for motor therapy for persons with disabilities
(2016) Journal of Intellectual Disability - Diagnosis and Treatment, 4 (3), pp. 140-141. 


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

 

 


Document Type: Editorial
Source: Scopus

 

24) 

Roediger, H.L., III
Varieties of Fame in Psychology
(2016) Perspectives on Psychological Science, 11 (6), pp. 882-887. 

DOI: 10.1177/1745691616662457


Washington University in St. Louis, United States


Abstract
Fame in psychology, as in all arenas, is a local phenomenon. Psychologists (and probably academics in all fields) often first become well known for studying a subfield of an area (say, the study of attention in cognitive psychology, or even certain tasks used to study attention). Later, the researcher may become famous within cognitive psychology. In a few cases, researchers break out of a discipline to become famous across psychology and (more rarely still) even outside the confines of academe. The progression is slow and uneven. Fame is also temporally constricted. The most famous psychologists today will be forgotten in less than a century, just as the greats from the era of World War I are rarely read or remembered today. Freud and a few others represent exceptions to the rule, but generally fame is fleeting and each generation seems to dispense with the lessons learned by previous ones to claim their place in the sun. © 2016, © The Author(s) 2016.


Author Keywords
fame in psychology;  forgetting;  history of psychology;  scientific eminence


Document Type: Article
Source: Scopus

 

25) 

Carter, A.R.a b , Foreman, M.H.b , Martin, C.b , Fitterer, S.b , Pioppo, A.b , Connor, L.T.b c , Engsberg, J.R.b 
Inducing visuomotor adaptation using virtual reality gaming with a virtual shift as a treatment for unilateral spatial neglect
(2016) Journal of Intellectual Disability - Diagnosis and Treatment, 4 (3), pp. 170-184. 

DOI: 10.6000/2292-2598.2016.04.03.4


a Department of Neurology, Washington University School of Medicine, Saint Louis, MO, United States
b Program in Occupational Therapy, Washington University School of Medicine, Saint Louis, MO, United States
c Department of Occupational Therapy, MGH Institute of Health Professions, Boston, MA, United States


Abstract
Unilateral spatial neglect after stroke is characterized by reduced responses to stimuli on the contralesional side, causing significant impairments in self-care and safety. Conventional visuomotor adaptation (VMA) with prisms that cause a lateral shift of the visual scene can decrease neglect symptoms but is not engaging according to patients. Performing VMA within a virtual reality (VR) environment may be more engaging but has never been tested. To determine if VMA can be elicited in a VR environment, healthy subjects (n=7) underwent VMA that was elicited by either wearing prisms that caused an optical shift, or by application of a virtual shift of the hand cursor within the VR environment. A low cost VR system was developed by coupling the Kinect v2 gaming sensor to online games via the Flexible Action and Articulated Skeleton Toolkit (FAAST) software. The adaptation phase of training consisted of a reaching task in online games or in a custom target pointing program. Following the adaptation phase the optical or virtual shift was removed and participants were assessed during the initial portion of the de-adaptation phase for the presence of an after-effect on their reaching movements, with lateral reaching errors indicating the successful induction of VMA. Results show that practicing reaching in a VR environment with a virtual shift lead to a horizontal after-effect similar to conventional prism adaptation. The results demonstrate that VMA can be elicited in a VR environment and suggest that VR gaming therapy could be used to improve recovery from unilateral spatial neglect. © 2016 Lifescience Global.


Author Keywords
Engagement;  Plasticity;  Sensorimotor learning;  Spatial attention;  Stroke


Document Type: Article
Source: Scopus

 

26) 

Mraz, K.a , Eisenberg, G.a , Diener, P.b , Amadio, G.a , Foreman, M.H.a , Engsberg, J.R.a 
The effects of virtual reality on the upper extremity skills of girls with rett syndrome: A single case study
(2016) Journal of Intellectual Disability - Diagnosis and Treatment, 4 (3), pp. 152-159. 

DOI: 10.6000/2292-2598.2016.04.03.2


a Washington University in St. Louis-School of Medicine, Program in Occupational Therapy, 4444 Forest Park Ave, Saint Louis, MO, United States
b Georgetown University-School of Medicine, Department of Neuroscience, 3970 Reservoir Rd NW, Washington, DC, United States


Abstract
Introduction: Rett Syndrome (RTT) is a genetic disorder primarily seen in females that inhibits the use of a girl's hands in everyday activities. A girl with RTT spends the majority of her day engaged in stereotypical hand wringing/mouthing movements at midline of the body. The probable cause behind the neurological effects of RTT is a mutation in the gene that encodes for methyl-CpG protein 2 (MeCP2). The hand wringing/mouthing behaviors preclude a girl with RTT from using the upper extremities in purposeful tasks such as school work, play skills, and other activities of daily living. Objectives: To develop a virtual reality (VR)-based therapeutic intervention that 1) decreases upper extremity stereotypies (repetitive movements that serve no function) that interfere with purposeful arm and hand use and 2) promotes purposeful, goal-directed arm function; improve upper extremity motor skills in girls with RTT. Materials and Methods: Using FAAST Software and Microsoft Kinect sensor, one girl with RTT participated in a 12-week IVR intervention (1 hour/session, 3 sessions/week, 36 total hours). Pre- and post-assessments were administered to examine any changes in upper extremity function. Results: The VR intervention led to improvements in use of the upper extremities to complete self-care activities, an increased number of reaches completed in a 15-minute period, and decreased time engaged in stereotypical hand movements. Conclusion: Future work will add additional support to determine the effectiveness of virtual reality as an intervention for girls with RTT. © 2016 Lifescience Global.


Author Keywords
Internet-based virtual reality;  Microsoft kinect;  Rett syndrome;  Upper extremity movements;  Upper extremity stereotypies


Document Type: Article
Source: Scopus

 

27) 

Bateman, R.J.a , Benzinger, T.L.b , Berry, S.c , Clifford, D.B.a , Duggan, C.a , Fagan, A.M.a , Fanning, K.a , Farlow, M.R.d , Hassenstab, J.a , McDade, E.M.a , Mills, S.a , Paumier, K.a , Quintana, M.c , Salloway, S.P.e , Santacruz, A.a , Schneider, L.S.f , Wang, G.g , Xiong, C.g 
The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model
(2016) Alzheimer's and Dementia, . Article in Press. 

DOI: 10.1016/j.jalz.2016.07.005


a Department of Neurology, Washington University in St Louis, St Louis, MO, USA
b Department of Radiology, Washington University in St Louis, St Louis, MO, USA
c Berry Consultants, Austin, TX, USA
d Indiana Alzheimer Disease Center, Indiana University, Indianapolis, IN, USA
e Memory and Aging Program, Butler Hospital, Brown Medical School, Providence, RI, USA
f Alzheimer's Disease Research Center, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
g Department of Biostatistics, Washington University in St Louis, St Louis, MO, USA


Abstract
Introduction: The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer's disease in autosomal dominant Alzheimer's disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation (NexGen) prevention trial. Methods: In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the National Institutes of Health, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen prevention trial. Results: Our expanded trial toolbox consists of a disease progression model for ADAD, primary end point DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion. Conclusion: These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD. © 2016 The Alzheimer's Association.


Author Keywords
Adaptive clinical trial;  Alzheimer's disease;  Alzheimer's prevention trial;  Amyloid;  Autosomal dominant Alzheimer's disease;  Biomarkers;  Cognitive composite;  DIAN-TU;  Disease progression model;  Dose adjustment;  Tau


Document Type: Article in Press
Source: Scopus

 

December 1, 2016

 

1) 

Spangler, S.M.a b c d , Bruchas, M.R.a b c d 
Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits
(2017) Current Opinion in Pharmacology, 32, pp. 56-70. 

DOI: 10.1016/j.coph.2016.11.001


a Department of Anesthesiology, Basic Research Division, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Optogenetics has revolutionized neuroscience by providing means to control cell signaling with spatiotemporal control in discrete cell types. In this review, we summarize four major classes of optical tools to manipulate neuromodulatory GPCR signaling: opsins (including engineered chimeric receptors); photoactivatable proteins; photopharmacology through caging — photoswitchable molecules; fluorescent protein based reporters and biosensors. Additionally, we highlight technologies to utilize these tools in vitro and in vivo, including Cre dependent viral vector expression and two-photon microscopy. These emerging techniques targeting specific members of the GPCR signaling pathway offer an expansive base for investigating GPCR signaling in behavior and disease states, in addition to paving a path to potential therapeutic developments. © 2016 The Author(s)


Document Type: Review
Source: Scopus

 

2) 

Ordikhani, F.a , Sheth, S.b , Zustiak, S.P.b 
Polymeric particle-mediated molecular therapies to treat spinal cord injury
(2017) International Journal of Pharmaceutics, 516 (1-2), pp. 71-81. 

DOI: 10.1016/j.ijpharm.2016.11.021


a Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, Saint Louis, MO, United States
b Biomedical Engineering, Parks College of Engineering, Aviation and Technology, Saint Louis University, 3507 Lindell Blvd., Saint Louis, MO, United States


Abstract
Spinal cord injury (SCI) is a physically and psychologically debilitating condition that mainly affects young, healthy males who are at the peak of their personal and professional development. SCI damages axons and disrupts myelination, which interrupts sensory and motor neuronal function. Current treatments are mostly palliative, aimed at reducing further damage and pain, but do not provide a cure. Polymeric particles have shown tremendous promise to provide patients with effective treatments that can bring partial or full functional recovery. Their unique properties can facilitate delivery of therapeutic agents to the injury site, provide protection from the host immunity or provide platforms to stimulate the regeneration of damaged axons. This review highlights the current benefits and challenges of the use of polymeric particles to control the release of molecular therapeutics as potential strategies for SCI treatment. © 2016 Elsevier B.V.


Author Keywords
Hydrogels;  Molecular therapy;  Neurotrophic factors;  Polymeric particle;  Spinal cord injury


Document Type: Review
Source: Scopus

 

3) 

Pita-Thomas, W.a b , Barroso-García, G.c , Moral, V.c , Hackett, A.R.d , Cavalli, V.b , Nieto-Diaz, M.a 
Identification of axon growth promoters in the secretome of the deer antler velvet
(2017) Neuroscience, 340, pp. 333-344. 

DOI: 10.1016/j.neuroscience.2016.10.063


a Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain
b Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO, United States
c Proteomics Core, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain
d The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, Miami, United States


Abstract
Every spring, deer cast their old antlers and initiate a regeneration process, which yields a new set of antlers of up to 1 m in length. Over the course of three months, branches of the trigeminal nerve, originating from the frontal skull, innervate velvet, a modified skin that covers the regenerating antler. The rate of growth of these axons reaches up to 2 cm per day making them the fastest regenerating axons in adult mammals. Here, we aim to identify the factors secreted by velvet that promote such high speed axon growth. Our experiments with cultures of adult rat trigeminal neurons demonstrate that conditioned medium harvested from velvet organotypic cultures has greater axon growth-promoting properties than a medium conditioned by normal skin. The axon growth-promoting effects of velvet act synergistically with the extracellular matrix (ECM) protein laminin, a component of the basal lamina present in the deer antler. Our proteomic analyses identified several axon growth promoters in the velvet-conditioned medium (VCM), including soluble proteins such as nerve growth factor (NGF) and apolipoprotein A-1, as well as matrix extracellular proteins, such as periostin and SPARC. Additional in vitro analyses allowed us to determine that a synergic relationship between periostin and NGF may contribute to neurite growth-promoting effects of velvet secretome. A combinatorial approach using these factors may promote regeneration at high speeds in patients with peripheral neuropathies. © 2016 IBRO


Author Keywords
axon regeneration;  deer antler;  peripheral nervous system;  proteomics;  secreted proteins


Document Type: Article
Source: Scopus

 

4) 

Balantekin, K.N.a , Birch, L.L.b , Savage, J.S.c 
Eating in the absence of hunger during childhood predicts self-reported binge eating in adolescence
(2017) Eating Behaviors, 24, pp. 7-10. 

DOI: 10.1016/j.eatbeh.2016.11.003


a Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 South Euclid Ave, St. Louis, MO, United States
b Department of Foods and Nutrition, The University of Georgia, Athens, GA, United States
c Department of Nutritional Sciences, The Pennsylvania State University, 110 Chandlee Laboratory, University ParkPA, United States


Abstract
Objective The objectives of the current study were to examine whether eating in the absence of hunger (EAH) at age 7 predicted reports of self-reported binge eating at age 15 and to identify factors among girls with high-EAH that moderated risk of later binge eating. Method Subjects included 158 girls assessed at age 7 and age 15. Logistic regression was used to predict binge eating at age 15 from calories consumed during EAH at age 7. A series of logistic regressions were used to examine the odds of reporting binge eating given levels of risk factors (e.g., anxiety) among those with high-EAH in childhood. Results Girls’ EAH intake predicted reports of binge eating at age 15; after adjusting for age 7 BMI, for each additional 100 kcal consumed, girls were 1.7 times more likely to report binge eating in adolescence. Among those with high-EAH, BMI, anxiety, depression, dietary restraint, emotional disinhibition, and body dissatisfaction all predicted binge eating. Discussion EAH during childhood predicted reports of binge eating during adolescence; girls with elevated BMI, negative affect, and maladaptive eating- and weight-related cognitions were at increased risk. High-EAH in childhood may be useful for indicating those at risk for developing binge eating. © 2016 Elsevier Ltd


Author Keywords
Adolescents;  Binge eating;  Eating in the absence of hunger


Document Type: Article
Source: Scopus

 

5) 

Greenberg, M.J.a b , Shuman, H.a , Ostap, E.M.a 
Measuring the kinetic and mechanical properties of non-processive myosins using optical tweezers
(2017) Methods in Molecular Biology, 1486, pp. 483-509. 

DOI: 10.1007/978-1-4939-6421-5_19


a Department of Physiology, The Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
b Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8231, St. Louis, MO, United States


Abstract
The myosin superfamily of molecular motors utilizes energy from ATP hydrolysis to generate force and motility along actin filaments in a diverse array of cellular processes. These motors are structurally, kinetically, and mechanically tuned to their specific molecular roles in the cell. Optical trapping techniques have played a central role in elucidating the mechanisms by which myosins generate force and in exposing the remarkable diversity of myosin functions. Here, we present thorough methods for measuring and analyzing interactions between actin and non-processive myosins using optical trapping techniques. © Springer Science+Business Media New York 2017.


Author Keywords
Actomyosin;  Kinetics;  Mechanochemistry;  Single molecule


Document Type: Book Chapter
Source: Scopus

 

6) 

Ceyhan, E.a , Nishino, T.b , Botteron, K.N.b c , Miller, M.I.d e f , Ratnanather, J.T.d e f 
Analysis of cortical morphometric variability using labeled cortical distance maps
(2017) Statistics and its Interface, 10 (2), pp. 313-341. 


a Dept. of Mathematics, Koç University, Sariyer, Istanbul, Turkey
b Dept. of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Dept. of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, United States
e Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, United States
f Dept. of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United States


Abstract
Morphometric (i.e., shape and size) differences in the anatomy of cortical structures are associated with neurodevelopmental and neuropsychiatric disorders. Such differences can be quantized and detected by a powerful tool called Labeled Cortical Distance Map (LCDM). The LCDM method provides distances of labeled gray matter (GM) voxels from the GM/white matter (WM) surface for specific cortical structures (or tissues). Here we describe a method to analyze morphometric variability in the particular tissue using LCDM distances. To extract more of the information provided by LCDM distances, we perform pooling and censoring of LCDM distances. In particular, we employ Brown-Forsythe (BF) test of homogeneity of variance (HOV) on the LCDM distances. HOV analysis of pooled distances provides an overall analysis of morphometric variability of the LCDMs due to the disease in question, while the HOV analysis of censored distances suggests the location( s) of significant variation in these differences (i.e., at which distance from the GM/WM surface the morphometric variability starts to be significant). We also check for the influence of assumption violations on the HOV analysis of LCDM distances. In particular, we demonstrate that BF HOV test is robust to assumption violations such as the non-normality and within sample dependence of the residuals from the median for pooled and censored distances and are robust to data aggregation which occurs in analysis of censored distances. We recommend HOV analysis as a complementary tool to the analysis of distribution/location differences. We also apply the methodology on simulated normal and exponential data sets and assess the performance of the methods when more of the underlying assumptions are satisfied. We illustrate the methodology on a real data example, namely, LCDM distances of GM voxels in ventral medial prefrontal cortices (VMPFCs) to see the effects of depression or being of high risk to depression on the morphometry of VMPFCs. The methodology used here is also valid for morphometric analysis of other cortical structures.


Author Keywords
Brown-Forsythe test;  Censoring;  Computational anatomy;  Homogeneity of variance;  Pooled distances;  Simultaneous inference


Document Type: Article
Source: Scopus

 

7) 

Van Patten, R.a b , Merz, Z.C.b , Mulhauser, K.b , Fucetola, R.a 
Multivariable Prediction of Return to Work at 6-Month Follow-Up in Patients With Mild to Moderate Acute Stroke
(2016) Archives of Physical Medicine and Rehabilitation, 97 (12), pp. 2061-2067.e1. 

DOI: 10.1016/j.apmr.2016.06.006


a Washington University School of Medicine, St Louis, MO, United States
b Saint Louis University, St Louis, MO, United States


Abstract
Objective To investigate predictors of return to work (RTW) in a poststroke sample. Design Retrospective investigation of archival data from an inception cohort; acute care records and 6-month follow-up telephone interview data were obtained for analysis. Setting The Brain Recovery Core, a collaborative interinstitutional endeavor among an academic medical center, an acute care hospital, and a rehabilitation center. Participants Data from patients with stroke from the Brain Recovery Core (N=298). Excluded cases included those with nontraditional and/or nonpaid job status, no National Institute of Health Stroke Scale (NIHSS) score, and an NIHSS score >16. Our final sample included 244 individuals (age range, 25–87y). Interventions Not applicable. Main Outcome Measures Sociodemographic variables, stroke severity (NIHSS), and physical and neurocognitive measures. Results Adding predictor variables to our logistic regression model increased accuracy by approximately 18%. Greater independence in the FIM sit-to-stand movement predicted improved RTW rates (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0–3.1), whereas nonwhite race (OR, 2.52; 95% CI, 1.16–5.47) and greater impairment on the NIHSS (OR,.88; 95% CI,.77–.99) predicted attenuated RTW rates. Conclusions Valid measures of stroke severity and a clinician-rated sit-to-stand movement have utility in the acute prediction of later RTW in patients with mild to moderate stroke. Given the complexity of the RTW construct and the acute measurement of these variables, we believe that our findings can be used to inform clinical decisions and appropriately tailor rehabilitative strategies that improve quality of life for stroke survivors. © 2016 American Congress of Rehabilitation Medicine


Author Keywords
Rehabilitation;  Return to work


Document Type: Article
Source: Scopus

 

8) 

Hendred, S.K.a , Foster, E.R.a b c 
Use of the World Health Organization Quality of Life Assessment Short Version in Mild to Moderate Parkinson Disease
(2016) Archives of Physical Medicine and Rehabilitation, 97 (12), pp. 2123-2129.e1. 

DOI: 10.1016/j.apmr.2016.05.020


a Program in Occupational Therapy, 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 Psychiatry, Washington University School of Medicine, St Louis, MO, United States


Abstract
Objective To investigate the distribution, internal consistency reliability, and convergent and discriminant validity of the World Health Organization Quality of Life Scale Brief Version (WHOQOL-BREF) in persons with mild to moderate Parkinson disease (PD). Design Cross-sectional. Setting Movement disorders center. Participants Convenience sample of people with PD (n=96) recruited from a movement disorders center and controls (n=60) recruited from the community (N=156). Interventions Not applicable. Main Outcome Measure WHOQOL-BREF. Results The WHOQOL-BREF domain data were relatively normally distributed, and internal consistency reliability was acceptable (α=.65–.85). Participants with PD reported lower quality of life (QOL) than controls in all except the environment domain, and physical QOL was the most impaired domain in the PD group. Age, fatigue, and physical activity limitations predicted physical QOL; depression, fatigue, and apathy predicted psychological QOL; education, executive dysfunction, and apathy predicted social QOL; and age, education, depression, and apathy predicted environment QOL. Conclusions The WHOQOL-BREF is a suitable tool to assess QOL in patients with mild to moderate PD. It is relatively normally distributed and internally consistent; effectively discriminates between individuals with and without PD; and correlates with relevant demographic characteristics, PD-related impairments, and activity limitations. © 2016 American Congress of Rehabilitation Medicine


Author Keywords
Parkinson disease;  Psychometrics;  Quality of life;  Rehabilitation


Document Type: Article
Source: Scopus

 

9) 

Head, D.a b d , Allison, S.a , Lucena, N.a , Hassenstab, J.a b c , Morris, J.C.b c 
Latent structure of cognitive performance in the adult children study
(2016) Journal of Clinical and Experimental Neuropsychology, pp. 1-16. Article in Press. 

DOI: 10.1080/13803395.2016.1252725


a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA
b Knight Alzheimer’s Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA
c Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA
d Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA


Abstract
Objective: The Adult Children Study (ACS) at the Knight Alzheimer’s Disease Research Center is a longitudinal investigation designed to identify and validate potential biomarkers of preclinical Alzheimer’s disease (AD) in cognitively normal individuals with and without a family history of AD. The purpose of the current study was to validate the proposed latent structure of the ACS psychometric battery. Method: Confirmatory factor analyses of baseline data in a sample of 229 (75 men) cognitively normal middle-aged to older adult individuals assessed a hypothesized 4-factor model of cognitive performance. Measurement invariance was investigated as a function of family history of AD and apolipoprotein E (APOE) status. Results: This study confirmed a priori hypotheses of 4 latent cognitive domains in a unique longitudinal sample of cognitively normal adults. In addition, there was evidence of a similar factor structure for family history and APOE status groups. Conclusion: These robust indicators of a broad range of cognitive domains will be used in future investigations to track the influence of family history of AD on cognitive performance over time. In addition, associations with fluid, structural, and molecular biomarkers of preclinical AD will be further examined, both cross-sectionally and longitudinally in this sample. © 2016 Informa UK Limited, trading as Taylor & Francis Group


Author Keywords
Cognitive aging;  Confirmatory factor analysis;  Measurement invariance;  Psychometric test battery


Document Type: Article in Press
Source: Scopus

 

10) 

Feuchtbaum, E., Buchowski, J., Zebala, L.
Subaxial cervical spine trauma
(2016) Current Reviews in Musculoskeletal Medicine, pp. 1-9. Article in Press. 

DOI: 10.1007/s12178-016-9377-0


Department of Orthopedic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8233, St. Louis, MO, United States


Abstract
Subaxial cervical spine trauma is common and an often missed diagnosis. Accurate and efficient diagnosis and management is necessary to avoid devastating complications such as spinal cord injury. Several classification schemes have been devised to help categorize fractures of the subaxial spine and define treatment algorithms. The Subaxial Cervical Spine Injury Classification System (SLIC) is widely used and evaluates not only fracture morphology but also considers ligamentous injury and neurological status in surgical decision making. However, interobserver reliability is poor, which proves to be the defining pitfall of this tool. More modern classification systems have been developed, which aim to improve the interobserver reliability; however, further large-scale studies are needed for more definitive evaluation. Overall, treatment of subaxial cervical spine injuries should include a protocol with initial trauma evaluation, leading to expedient operative intervention if indicated. Surgical techniques include both anterior and posterior approaches to the cervical spine depending on fracture classification. © 2016 Springer Science+Business Media New York


Author Keywords
Classification system;  Fracture;  Ligamentous injury;  Subaxial cervical spine trauma


Document Type: Article in Press
Source: Scopus

 

11) 

Huberty, J.a , Leiferman, J.A.b , Kruper, A.R.c , Jacobson, L.T.d , Waring, M.E.e , Matthews, J.L.a , Wischenka, D.M.f , Braxter, B.g , Kornfield, S.L.h 
Exploring the need for interventions to manage weight and stress during interconception
(2016) Journal of Behavioral Medicine, pp. 1-14. Article in Press. 

DOI: 10.1007/s10865-016-9813-z


a School of Nutrition and Health Promotion, Arizona State University, Phoenix, AZ, United States
b Colorado School of Public Health, University of Colorado Denver, Aurora, CO, United States
c Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, United States
d Department of Preventive Medicine and Public Health, University of Kansas School of Medicine-Wichita, Wichita, KS, United States
e Departments of Quantitative Health Sciences and Obstetrics and Gynecology, University of Massachusetts Medical School, Worcester, MA, United States
f Graduate School of Psychology, Yeshiva University Ferkauf, Bronx, NY, United States
g School of Nursing, University of Pittsburg, Pittsburgh, PA, United States
h Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Interventions to manage weight and stress during the interconception period (i.e., time immediately following childbirth to subsequent pregnancy) are needed to promote optimal maternal and infant health outcomes. To address this gap, we summarize the current state of knowledge, critically evaluate the research focused on weight and stress management during the interconception period, and provide future recommendations for research in this area. Evidence supports the importance of weight and stress management during the reproductive years and the impact of weight on maternal and child health outcomes. However, evidence-based treatment models that address postpartum weight loss and manage maternal stress during the interconception period are lacking. This problem is further compounded by inconsistent definitions and measurements of stress. Recommendations for future research include interventions that address weight and stress tailored for women in the interconception period, interventions that address healthcare providers’ understanding of the significance of weight and stress management during interconception, and long-term follow-up studies that focus on the public health implications of weight and stress management during interconception. Addressing obesity and stress during the interconception period via a reproductive lens will be a starting point for women and their families to live long and healthy lives. © 2016 Springer Science+Business Media New York


Author Keywords
Interconception;  Maternal weight gain;  Obesity;  Pregnancy;  Stress;  Women’s health


Document Type: Article in Press
Source: Scopus

 

12) 

Carney, R.M., Freedland, K.E.
Depression and coronary heart disease
(2016) Nature Reviews Cardiology, . Article in Press. 

DOI: 10.1038/nrcardio.2016.181


Washington University School of Medicine, 4320 Forest Park Avenue, Suite 301, St. Louis, Missouri 63108, USA.


Abstract
Depression is a highly prevalent risk factor for incident coronary heart disease (CHD) and for cardiovascular morbidity and mortality in patients with established CHD. Several biological and behavioural mechanisms have been hypothesized to underlie the relationship between depression and CHD, but none has been shown to account for more than a small proportion of the risk. Only a few clinical trials have examined whether treating depression decreases the risk of cardiac events in patients with established CHD. None of these trials has shown that treatment results in improved cardiac outcomes, but the differences in depression outcomes between the intervention and control groups have been small and not clinically significant. Nevertheless, secondary analyses of these trials suggest that prognosis improves when depression improves. Concerted efforts to develop more potent interventions for depression, identification of high-risk subtypes of depression, and further research on the biobehavioural mechanisms linking depression to CHD are needed to pave the way for definitive clinical trials. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Document Type: Article in Press
Source: Scopus

 

13) 

Blennow, K.a b , Brody, D.L.c , Kochanek, P.M.d , Levin, H.e f , McKee, A.g h , Ribbers, G.M.i j , Yaffe, K.k l , Zetterberg, H.a b m 
Traumatic brain injuries
(2016) Nature Reviews Disease Primers, 2, art. no. 16084, . 

DOI: 10.1038/nrdp.2016.84


a Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Molndal, Sweden
b Clinical Neurochemistry Laboratory, Sahlgrenska University, Gothenburg, Sweden
c Department of Neurology, Washington University, School of Medicine in Saint Louis, St. Louis, MI, United States
d Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, United States
e Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, United States
f Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, United States
g Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA, United States
h Departments of Neurology, Pathology and Laboratory Medicine, Boston University, Boston, MA, United States
i Department of Rehabilitation Medicine, Erasmus University, Medical Centre, Rotterdam, Netherlands
j Rijndam Rehabilitation Center, Rotterdam, Netherlands
k Departments of Psychiatry, Neurology, University of California, San Francisco, CA, United States
l Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, United States
m Institute of Neurology, University College London, London, United Kingdom


Abstract
Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury-the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available. Most patients with mild TBI will recover quickly, but others report persistent symptoms, called post-concussive syndrome, the underlying pathophysiology of which is largely unknown. Repeated concussive and subconcussive head injuries have been linked to the neurodegenerative condition chronic traumatic encephalopathy (CTE), which has been reported post-mortem in contact sports athletes and soldiers exposed to blasts. Insights from severe injuries and CTE plausibly shed light on the underlying cellular and molecular processes involved in mild TBI. MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE. Given that CTE is attributed to repeated head trauma, prevention might be possible through rule changes by sports organizations and legislators. © 2016 Macmillan Publishers Limited, part of Springer Nature.


Document Type: Article
Source: Scopus

 

14) 

Gillentine, M.A.a b , Berry, L.N.c d , Goin-Kochel, R.P.c d , Ali, M.A.a b , Ge, J.a , Guffey, D.e , Rosenfeld, J.A.a , Hannig, V.f , Bader, P.g , Proud, M.d h , Shinawi, M.i , Graham, B.H.a , Lin, A.j , Lalani, S.R.a , Reynolds, J.k , Chen, M.l , Greb, T.m , Minard, C.G.e , Stankiewicz, P.a , Beaudet, A.L.a , Schaaf, C.P.a b 
The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications
(2016) Journal of Autism and Developmental Disorders, pp. 1-14. Article in Press. 

DOI: 10.1007/s10803-016-2961-8


a Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States
b Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Moursund Street, Ste. 1325, Houston, TX, United States
c Autism Center, Texas Children’s Hospital, Houston, TX, United States
d Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
e Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, United States
f Department of Pediatrics, Vanderbilt University Medical Center, Nashville, United States
g Northeast Indiana Genetics, Fort Wayne, IN, United States
h Department of Neurology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United States
i Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
j Medical Genetics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, United States
k Medical Genetics, Shodair Children’s Hospital, Helena, MT, United States
l Department of Pediatrics-Diabetes and Endocrinology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United States
m Department of Child Health, Division of Genetics and Metabolism, Phoenix Children’s Hospital, University of Arizona College of Medicine, Phoenix, AZ, United States


Abstract
Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene. However, the pathogenicity of duplications of CHRNA7 is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving CHRNA7, identified by clinical chromosome microarray analysis (CMA). Comprehensive phenotyping revealed high prevalence of developmental delay/intellectual disability, autism spectrum disorder, and attention deficit/hyperactivity disorder. As CHRNA7 duplications are the most common CNVs identified by clinical CMA, this study provides anticipatory guidance for those involved with care of affected individuals. © 2016 Springer Science+Business Media New York


Author Keywords
15q13.3 microduplication;  Autism spectrum disorder;  Behavior;  CHRNA7;  Neurodevelopment


Document Type: Article in Press
Source: Scopus

 

15) 

Griggs, R.C.a , Miller, J.P.b , Greenberg, C.R.c , Fehlings, D.L.d , Pestronk, A.b , Mendell, J.R.a , Moxley, R.T.a , King, W.f , Kissel, J.T.f , Cwik, V.g , Vanasse, M.h , Florence, J.M.b , Pandya, S.a , Dubow, J.S.i , Meyer, J.M.e i i 
Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy
(2016) Neurology, 87 (20), pp. 2123-2131. 

DOI: 10.1212/WNL.0000000000003217


a University of Rochester Medical CenterNY, United States
b Washington University in St Louis, MO, United States
c University of Manitoba and Children's Hospital Research Institute of Manitoba, Winnipeg, Canada
d Department of Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, University of Toronto, Canada
e Nationwide Children's Hospital, United States
f Ohio State University Wexner Medical Center, Columbus, United States
g Muscular Dystrophy Association, Marlton, NJ, United States
h CHU Sainte Justine, Montreal, Canada
i Marathon Pharmaceuticals, LLC, Northbrook, IL, United States


Abstract
Objective: To assess safety and efficacy of deflazacort (DFZ) and prednisone (PRED) vs placebo in Duchenne muscular dystrophy (DMD). Methods: This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated muscle strength among 196 boys aged 5-15 years with DMD during a 52-week period. In phase 1, participants were randomly assigned to receive treatment with DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, PRED 0.75 mg/kg/d, or placebo for 12 weeks. In phase 2, placebo participants were randomly assigned to 1 of the 3 active treatment groups. Participants originally assigned to an active treatment continued that treatment for an additional 40 weeks. The primary efficacy endpoint was average change in muscle strength from baseline to week 12 compared with placebo. The study was completed in 1995. Results: All treatment groups (DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, and PRED 0.75 mg/kg/d) demonstrated significant improvement in muscle strength compared with placebo at 12 weeks. Participants taking PRED had significantly more weight gain than placebo or both doses of DFZ at 12 weeks; at 52 weeks, participants taking PRED had significantly more weight gain than both DFZ doses. The most frequent adverse events in all 3 active treatment arms were Cushingoid appearance, erythema, hirsutism, increased weight, headache, and nasopharyngitis. Conclusions: After 12 weeks of treatment, PRED and both doses of DFZ improved muscle strength compared with placebo. Deflazacort was associated with less weight gain than PRED. Classification of evidence: This study provides Class I evidence that for boys with DMD, daily use of either DFZ and PRED is effective in preserving muscle strength over a 12-week period. © 2016 American Academy of Neurology.


Document Type: Article
Source: Scopus

 

16) 

Peterson, D.A.a c d , Littlewort, G.C.c d e , Bartlett, M.S.c e , Macerollo, A.g , Perlmutter, J.S.c h , Jinnah, H.A.i , Hallett, M.j , Sejnowski, T.J.a b f 
Objective, computerized video-based rating of blepharospasm severity
(2016) Neurology, 87 (20), pp. 2146-2153. 

DOI: 10.1212/WNL.0000000000003336


a Computational Neurobiology Laboratory, United States
b Howard Hughes Medical Institute, Salk Institute for Biological Studies, United States
c Institute for Neural Computation, United States
d Kavli Institute for Brain and Mind, United States
e Machine Perception Laboratory, United States
f Division of Biological Sciences, University of California, San Diego, United States
g Sobell Department of Motor Neuroscience and Movement Disorders, National Hospital of Neurology and Neurosurgery, Institute of Neurology, University College London, United Kingdom
h Departments of Neurology, Radiology, and Anatomy and Neurobiology, Programs in Physical Therapy and Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
i Departments of Neurology, Human Genetics, and Pediatrics, Emory University, Atlanta, GA, United States
j Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, United States


Abstract
Objective: To compare clinical rating scales of blepharospasm severity with involuntary eye closures measured automatically from patient videos with contemporary facial expression software. Methods: We evaluated video recordings of a standardized clinical examination from 50 patients with blepharospasm in the Dystonia Coalition's Natural History and Biorepository study. Eye closures were measured on a frame-by-frame basis with software known as the Computer Expression Recognition Toolbox (CERT). The proportion of eye closure time was compared with 3 commonly used clinical rating scales: the Burke-Fahn-Marsden Dystonia Rating Scale, Global Dystonia Rating Scale, and Jankovic Rating Scale. Results: CERT was reliably able to find the face, and its eye closure measure was correlated with all of the clinical severity ratings (Spearman ρ 0.56, 0.52, and 0.56 for the Burke-Fahn-Marsden Dystonia Rating Scale, Global Dystonia Rating Scale, and Jankovic Rating Scale, respectively, all p < 0.0001). Conclusions: The results demonstrate that CERT has convergent validity with conventional clinical rating scales and can be used with video recordings to measure blepharospasm symptom severity automatically and objectively. Unlike EMG and kinematics, CERT requires only conventional video recordings and can therefore be more easily adopted for use in the clinic. © 2016 American Academy of Neurology.


Document Type: Article
Source: Scopus

 

17) 

Monsell, S.E., Mock, C., Fardo, D.W., Bertelsen, S., Cairns, N.J., Roe, C.M., Ellingson, S.R., Morris, J.C., Goate, A.M., Kukull, W.A.
Genetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology
(2016) Alzheimer Disease and Associated Disorders, . Article in Press. 

DOI: 10.1097/WAD.0000000000000179


*Department of Biostatistics †National Alzheimer’s Coordinating Center, University of Washington, Seattle, WA ‡Department of Biostatistics, University of Kentucky, Lexington, KY §Dept. of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY ?Department of Neurology, Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MI


Abstract
OBJECTIVE:: The objective was to determine whether symptomatic and asymptomatic persons with Alzheimer’s disease (AD) neuropathology have different allele counts for single-nucleotide polymorphisms that have been associated with clinical late-onset AD. METHODS:: Data came from the National Alzheimer’s Coordinating Center Uniform Data Set and Neuropathology Data Set, and the Alzheimer’s Disease Genetics Consortium (ADGC). Participants had low to high AD neuropathologic change. The 22 known/suspected genes associated with late-onset AD were considered. “Symptomatic” was defined as Clinical Dementia Rating global score >0. RESULTS:: Sixty-eight asymptomatic and 521 symptomatic participants met inclusion criteria. Single-nucleotide polymorphisms associated with ABCA7 [odds ratio (OR)=1.66; 95% confidence interval (CI), 1.03-2.85] and MAPT (OR=2.18; CI, 1.26-3.77) were associated with symptomatic status. In stratified analyses, loci containing CD2AP (OR=0.35; 95% CI, 0.16-0.74), ZCWPW1 (OR=2.98; 95% CI, 1.34-6.86), and MAPT (OR=3.73, 95% CI, 1.30-11.76) were associated with symptomatic status in APOE e4 carriers. CONCLUSIONS:: These findings potentially explain some of the variation in whether a person with AD neuropathology expresses symptoms. Understanding why some people remain cognitively normal despite having AD neuropathology could identify pathways to disease heterogeneity and guide treatment trials. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved


Document Type: Article in Press
Source: Scopus

 

18) 

Rogers, C.S.a b 
Semantic priming, not repetition priming, is to blame for false hearing
(2016) Psychonomic Bulletin and Review, pp. 1-11. Article in Press. 

DOI: 10.3758/s13423-016-1185-4


a Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Otolaryngology, Washington University in St. Louis, 660 South Euclid, Box 8115, St. Louis, MO, United States


Abstract
Contextual and sensory information are combined in speech perception. Conflict between the two can lead to false hearing, defined as a high-confidence misidentification of a spoken word. Rogers, Jacoby, and Sommers (Psychology and Aging, 27(1), 33–45, 2012) found that older adults are more susceptible to false hearing than are young adults, using a combination of semantic priming and repetition priming to create context. In this study, the type of context (repetition vs. sematic priming) responsible for false hearing was examined. Older and young adult participants read and listened to a list of paired associates (e.g., ROW–BOAT) and were told to remember the pairs for a later memory test. Following the memory test, participants identified words masked in noise that were preceded by a cue word in the clear. Targets were semantically associated to the cue (e.g., ROW–BOAT), unrelated to the cue (e.g., JAW–PASS), or phonologically related to a semantic associate of the cue (e.g., ROW–GOAT). How often each cue word and its paired associate were presented prior to the memory test was manipulated (0, 3, or 5 times) to test effects of repetition priming. Results showed repetitions had no effect on rates of context-based listening or false hearing. However, repetition did significantly increase sensory information as a basis for metacognitive judgments in young and older adults. This pattern suggests that semantic priming dominates as the basis for false hearing and highlights context and sensory information operating as qualitatively different bases for listening and metacognition. © 2016 Psychonomic Society, Inc.


Author Keywords
Cognitive aging;  False memory;  Metamemory;  Speech perception


Document Type: Article in Press
Source: Scopus

 

19) 

Huang, J.a , Samson, P.b , Perkins, S.M.a , Ansstas, G.c , Chheda, M.G.c , DeWees, T.A.a , Tsien, C.I.a , Robinson, C.G.a , Campian, J.L.c 
Impact of concurrent chemotherapy with radiation therapy for elderly patients with newly diagnosed glioblastoma: a review of the National Cancer Data Base
(2016) Journal of Neuro-Oncology, pp. 1-9. Article in Press. 

DOI: 10.1007/s11060-016-2331-6


a Department of Radiation Oncology, Center for Advanced Medicine, Washington University School of Medicine, 4921 Parkview Place, Campus Box #8224, St. Louis, MO, United States
b Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
c Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
To investigate the utilization and overall survival (OS) impact of concurrent chemotherapy in combination with radiation therapy (RT) for elderly glioblastoma (GBM) patients. Elderly patients (age >70) with supratentorial and nonmetastatic GBM who received RT of 20–75 Gy with concurrent single-agent chemotherapy (ChemoRT) or without (RT alone) during 2004–2012 were identified from the National Cancer Data Base (NCDB). The Cochran-Armitage test was used for trend analysis. Hazard ratios (HR) and 95% confidence intervals (CIs) were determined using Cox proportional hazards. Propensity score analysis was performed to reduce selection bias in treatment allocation. A total of 5252 patients were identified (RT alone: n = 1389; ChemoRT: n = 3863). There was increasing utilization of chemotherapy during this period (45–80%, P < .001). A similar trend was also observed for the subset of age >80 (25–68%, P < .001). ChemoRT was associated with significantly better OS than RT alone (HR 0.79, 95% CI 0.70–0.89, P < .001) on multivariate analysis, and similar OS benefit was demonstrated with 1202 pairs of propensity-matched patients (HR 0.79, 95% CI 0.73–0.86, P < .001). For the matched pair, the median OS was 5.8 months with ChemoRT and 5.0 months with RT alone; the 2-year OS rate was 9% with ChemoRT and 4% with RT alone (P < .001). Concurrent chemotherapy has been administered with RT for the majority of elderly GBM patients. Addition of chemotherapy to RT for elderly GBM patients is associated with significantly improve OS in routine clinical practice. © 2016 Springer Science+Business Media New York


Author Keywords
Chemotherapy;  Elderly;  GBM;  NCDB;  Radiation therapy


Document Type: Article in Press
Source: Scopus

 

20) 

Deming, Y.a , Black, K.a , Carrell, D.a , Cai, Y.a , Del-Aguila, J.L.a , Fernandez, M.V.a , Budde, J.a , Ma, S.M.a , Saef, B.a , Howells, B.a , Bertelsen, S.b , Huang, K.-L.c , Sutphen, C.L.d , Tarawneh, R.d e f , Fagan, A.M.d e f , Holtzman, D.M.d e f g , Morris, J.C.d e f g , Goate, A.M.b , Dougherty, J.D.a c , Cruchaga, C.a f 
Chitinase-3-like 1 protein (CHI3L1) locus influences cerebrospinal fluid levels of YKL-40
(2016) BMC Neurology, 16 (1), art. no. 217, . 

DOI: 10.1186/s12883-016-0742-9


a Washington University School of Medicine, Department of Psychiatry, 660 S. Euclid Ave. B8134, St. Louis, MO, United States
b Ronald M. Loeb Center for Alzheimer's disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
c Washington University School of Medicine, Department of Genetics, 660 S. Euclid Ave., St. Louis, MO, United States
d Washington University School of Medicine, Department of Neurology, 660 S. Euclid Ave., St. Louis, MO, United States
e Washington University School of Medicine, Knight Alzheimer's Disease Research Center, 660 S. Euclid Ave., St. Louis, MO, United States
f Washington University School of Medicine, Hope Center for Neurological Disorders, 660 S. Euclid Ave. B8111, St. Louis, MO, United States
g Washington University School of Medicine, Department of Developmental Biology, 660 S. Euclid Ave., St. Louis, MO, United States


Abstract
Background: Alzheimer's disease (AD) pathology appears several years before clinical symptoms, so identifying ways to detect individuals in the preclinical stage is imperative. The cerebrospinal fluid (CSF) Tau/Aβ42 ratio is currently the best known predictor of AD status and cognitive decline, and the ratio of CSF levels of chitinase-3-like 1 protein (CHI3L1, YKL-40) and amyloid beta (Aβ42) were reported as predictive, but individual variability and group overlap inhibits their utility for individual diagnosis making it necessary to find ways to improve sensitivity of these biomarkers. Methods: We used linear regression to identify genetic loci associated with CSF YKL-40 levels in 379 individuals (80 cognitively impaired and 299 cognitively normal) from the Charles F and Joanne Knight Alzheimer's Disease Research Center. We tested correlations between YKL-40 and CSF Tau/Aβ42 ratio, Aβ42, tau, and phosphorylated tau (ptau181). We used studentized residuals from a linear regression model of the log-transformed, standardized protein levels and the additive reference allele counts from the most significant locus to adjust YKL-40 values and tested the differences in correlations with CSF Tau/Aβ42 ratio, Aβ42, tau, and ptau181. Results: We found that genetic variants on the CH13L1 locus were significantly associated with CSF YKL-40 levels, but not AD risk, age at onset, or disease progression. The most significant variant is a reported expression quantitative trait locus for CHI3L1, the gene which encodes YKL-40, and explained 12.74 % of the variance in CSF YKL-40 in our study. YKL-40 was positively correlated with ptau181 (r=0.521) and the strength of the correlation significantly increased with the addition of genetic information (r=0.573, p=0.006). Conclusions: CSF YKL-40 levels are likely a biomarker for AD, but we found no evidence that they are an AD endophenotype. YKL-40 levels are highly regulated by genetic variation, and by including genetic information the strength of the correlation between YKL-40 and ptau181 levels is significantly improved. Our results suggest that studies of potential biomarkers may benefit from including genetic information. © 2016 The Author(s).


Author Keywords
Alzheimer disease;  Cerebrospinal fluid;  CHI3L1;  YKL-40


Document Type: Article
Source: Scopus

 

21) 

Poppler, L.H.a , Groves, A.P.b , Sacks, G.b , Bansal, A.b , Davidge, K.M.c , Sledge, J.A.d , Tymkew, H.d , Yan, Y.e , Hasak, J.M.e , Potter, P.d , Mackinnon, S.E.a 
Subclinical peroneal neuropathy: A common, unrecognized, and preventable finding associated with a recent history of falling in hospitalized patients
(2016) Annals of Family Medicine, 14 (6), pp. 526-533. Cited 1 time.

DOI: 10.1370/afm.1973


a Division of Plastic & Reconstructive Surgery, Washington University, St Louis School of Medicine, St Louis, MO, United States
b Washington University, St Louis School of Medicine, St Louis, MO, United States
c The Hospital for Sick Children, Toronto, ON, Canada
d BJC HealthCare, St Louis, MO, United States
e Department of Surgery, Washington University, St Louis School of Medicine, St Louis, MO, United States


Abstract
PURPOSE Identification of modifiable risk factors for falling is paramount in reducing the incidence and morbidity of falling. Peroneal neuropathy with an overt foot drop is a known risk factor for falling, but research into subclinical peroneal neuropathy (SCPN) resulting from compression at the fibular head is lacking. The purpose of our study was to determine the prevalence of SCPN in hospitalized patients and establish whether it is associated with a recent history of falling. METHODS We conducted a cross-sectional study of 100 medical inpatients at a large academic tertiary care hospital in St Louis, Missouri. General medical inpatients deemed at moderate to high risk for falling were enrolled in the summer of 2013. Patients were examined for findings that suggest peroneal neuropathy, fall risk, and a history of falling. Multivariate logistic regression was used to correlate SCPN with fall risk and a history of falls in the past year. RESULTS The mean patient age was 53 years (SD= 13 years), and 59 patients (59%) were female. Thirty-one patients had examination findings consistent with SCPN. After accounting for various confounding variables within a multivariate logistic regression model, patients with SCPN were 4.7 times (95% CI, 1.4-15.9) more likely to report having fallen 1 or more times in the past year. CONCLUSIONS Subclinical peroneal neuropathy is common in medical inpatients and is associated with a recent history of falling. Preventing or identifying SCPN in hospitalized patients provides an opportunity to modify activity and therapy, potentially reducing risk. © 2016, Annals of Family Medicine, Inc. All rights reserved.


Author Keywords
Accidental;  Common peroneal;  Falls;  Nerve compression syndromes;  Neuropathy;  Peroneal nerve diseases;  Peroneal nerve paralysis;  Preventive medicine


Document Type: Article
Source: Scopus

 

22) 

Johanns, T.M.a b , Miller, C.A.c d , Dorward, I.G.e , Tsien, C.f , Chang, E.g , Perry, A.g h , Uppaluri, R.i , Ferguson, C.j, Schmidt, R.E.j , Dahiya, S.j , Ansstas, G.a b k , Mardis, E.R.c d k , Dunn, G.P.b e k 
Immunogenomics of hypermutated glioblastoma: A patient with germline POLE deficiency treated with checkpoint blockade immunotherapy
(2016) Cancer Discovery, 6 (11), pp. 1230-1236. Cited 1 time.

DOI: 10.1158/2159-8290.CD-16-0575


a Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Washington University School of Medicine, St. Louis, MO, United States
c McDonnell Genome Institute, Washington University, St. Louis, MO, United States
d Division of Genomics and Bioinformatics, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
f Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States
h Department of Pathology, University of California, San Francisco, San Francisco, CA, United States
i Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States
j Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
k The Alvin J. Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO, United States


Abstract
We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment. Furthermore, a persistently high neoantigen load was observed within all tumors. Interestingly, following initiation of pembrolizumab, brisk lymphocyte infiltration was observed in the subsequently resected metastatic spinal lesion and an objective radiographic response was noted in a progressive intracranial lesion, suggestive of active central nervous system (CNS) immunosurveillance following checkpoint blockade therapy. SIGNIFICANCE: It is unclear whether hypermutated glioblastomas are susceptible to checkpoint blockade in adults. Herein, we provide proof of principle that glioblastomas with DNA-repair defects treated with checkpoint blockade may result in CNS immune activation, leading to clinically and immunologically significant responses. These patients may represent a genomically stratified group for whom immunotherapy could be considered. © 2016 American Association for Cancer Research.


Document Type: Article
Source: Scopus

 

23) 

Scholz, N.a , Monk, K.R.b , Kittel, R.J.a , Langenhan, T.a 
Adhesion GPCRs as a putative class of metabotropic mechanosensors
(2016) Handbook of Experimental Pharmacology, 234, pp. 221-247. 

DOI: 10.1007/978-3-319-41523-9_10


a Department of Neurophysiology, Institute of Physiology, University of Würzburg, Röntgenring 9, Würzburg, Germany
b Department of Developmental Biology, Hope Center for Neurologic Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
G protein-coupled receptors (GPCRs) constitute the most versatile superfamily of biosensors. This group of receptors is formed by hundreds of GPCRs, each of which is tuned to the perception of a specific set of stimuli a cell may encounter emanating from the outside world or from internal sources. Most GPCRs are receptive for chemical compounds such as peptides, proteins, lipids, nucleotides, sugars, and other organic compounds, and this capacity is utilized in several sensory organs to initiate visual, olfactory, gustatory, or endocrine signals. In contrast, GPCRs have only anecdotally been implicated in the perception of mechanical stimuli. Recent studies, however, show that the family of adhesion GPCRs (aGPCRs), which represents a large panel of over 30 homologs within the GPCR superfamily, displays molecular design and expression patterns that are compatible with receptivity toward mechanical cues (Fig. 1). Here, we review physiological and molecular principles of established mechanosensors, discuss their relevance for current research of the mechanosensory function of aGPCRs, and survey the current state of knowledge on aGPCRs as mechanosensing molecules. © Springer International Publishing AG 2016.


Author Keywords
Adhesion GPCR;  Mechanosensation;  Mechanosensor


Document Type: Book Chapter
Source: Scopus

 

24) 

Sigoillot, S.M.a , Monk, K.R.b , Piao, X.c , Selimi, F.a , Harty, B.L.b 
Adhesion GPCRs as novel actors in neural and glial cell functions: From synaptogenesis to myelination
(2016) Handbook of Experimental Pharmacology, 234, pp. 275-298. 

DOI: 10.1007/978-3-319-41523-9_12


a Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France
b Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
c Division of Newborn Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States


Abstract
Adhesion G-protein-coupled receptors (aGPCRs) are emerging as key regulators of nervous system development and health. aGPCRs can regulate many aspects of neural development, including cell signaling, cell-cell and cell-matrix interactions, and, potentially, mechanosensation. Here, we specifically focus on the roles of several aGPCRs in synapse biology, dendritogenesis, and myelinating glial cell development. The lessons learned from these examples may be extrapolated to other contexts in the nervous system and beyond. © Springer International Publishing AG 2016.


Author Keywords
Adhesion GPCR;  Dendritogenesis;  Myelination;  Neurodevelopment;  Synaptogenesis


Document Type: Book Chapter
Source: Scopus

 

25) 

Burgess, G.C.a , Kandala, S.b , Nolan, D.b , Laumann, T.O.c , Power, J.D.d , Adeyemo, B.c , Harms, M.P.b , Petersen, S.E.a c e f , Barch, D.M.b e f 
Evaluation of Denoising Strategies to Address Motion-Correlated Artifacts in Resting-State Functional Magnetic Resonance Imaging Data from the Human Connectome Project
(2016) Brain Connectivity, 6 (9), pp. 669-680. 

DOI: 10.1089/brain.2016.0435


a Department of Neuroscience, Washington University School of Medicine, Campus Box 8225, St. Louis, MO, United States
b Department of Psychiatry, 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 National Institute of Mental Health, Bethesda, MD, United States
e Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Like all resting-state functional connectivity data, the data from the Human Connectome Project (HCP) are adversely affected by structured noise artifacts arising from head motion and physiological processes. Functional connectivity estimates (Pearson's correlation coefficients) were inflated for high-motion time points and for high-motion participants. This inflation occurred across the brain, suggesting the presence of globally distributed artifacts. The degree of inflation was further increased for connections between nearby regions compared with distant regions, suggesting the presence of distance-dependent spatially specific artifacts. We evaluated several denoising methods: censoring high-motion time points, motion regression, the FMRIB independent component analysis-based X-noiseifier (FIX), and mean grayordinate time series regression (MGTR; as a proxy for global signal regression). The results suggest that FIX denoising reduced both types of artifacts, but left substantial global artifacts behind. MGTR significantly reduced global artifacts, but left substantial spatially specific artifacts behind. Censoring high-motion time points resulted in a small reduction of distance-dependent and global artifacts, eliminating neither type. All denoising strategies left differences between high- and low-motion participants, but only MGTR substantially reduced those differences. Ultimately, functional connectivity estimates from HCP data showed spatially specific and globally distributed artifacts, and the most effective approach to address both types of motion-correlated artifacts was a combination of FIX and MGTR. © Copyright 2016, Mary Ann Liebert, Inc. 2016.


Author Keywords
artifact;  denoising;  fMRI;  functional connectivity;  Human Connectome Project;  independent component analysis;  motion;  resting state


Document Type: Article
Source: Scopus

 

26) 

Avedschmidt, S.E.a , Stagner, A.M.b c , Eagle, R.C., Jr.d , Harocopos, G.J.e f , Dou, Y.a g h , Rao, R.C.a h i j k 
The targetable epigenetic tumor protein EZH2 is enriched in intraocular medulloepithelioma
(2016) Investigative Ophthalmology and Visual Science, 57 (14), pp. 6242-6246. 

DOI: 10.1167/iovs.16-20463


a Department of Pathology, University of Michigan, Ann Arbor, MI, United States
b Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States
c Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
d Department of Ophthalmic Pathology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, United States
e Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
f Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, United States
h Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, United States
i Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI, United States
j A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, MI, United States
k Section of Ophthalmology, Surgical Service, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, MI, United States


Abstract
PURPOSE. Intraocular medulloepithelioma (IM), the second most common primary neuroepithelial tumor of the eye, can lead to blindness in the affected eye and in rare cases, is deadly. Intraocular medulloepithelioma lacks targetable biomarkers for potential pharmacologic therapy. The purpose of this study was to identify actionable, tumor-specific proteins for potential diagnostic or therapeutic strategies. We hypothesize that the tumor-specific epigenetic enzyme EZH2 is selectively expressed in IM. METHODS. We conducted a retrospective case series study of five IM from five eyes of four children and one adult. Hematoxylin and eosin (H&E) stains of sections from formalin-fixed, paraffin-embedded blocks of IM tumors were used to localize IM tumor cells in each case. Using an EZH2-specific antibody for immunohistochemistry, we semiquantitatively calculated the proportion of IM tumor cells positive for EZH2, and also assayed for EZH2 staining intensity. RESULTS. We found that EZH2 was expressed in all IM cases but this protein was absent in nontumor ciliary body or retinal tissues. However, not all IM tumor cells expressed EZH2. Similar to retinoblastoma, moderately to poorly differentiated (primitive appearing) IM tumor cells strongly expressed EZH2; expression was weaker or absent in areas of well-formed neuroepithelial units. CONCLUSIONS. To our knowledge, this is the first study to identify an actionable tumor-specific maker, EZH2, in IM. Our findings point to the possibility of exploring the potential of EZH2 inhibitors, already in clinical trials for other cancers, for IM. © 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.


Author Keywords
Epigenetics;  EZH2;  Medulloepithelioma


Document Type: Article
Source: Scopus

 

27) 

How, J.a , Blattner, M.a , Fowler, S.b , Wang-Gillam, A.c , Schindler, S.E.d 
Chemotherapy-associated Posterior Reversible Encephalopathy Syndrome: A Case Report and Review of the Literature
(2016) Neurologist, 21 (6), pp. 112-117. 

DOI: 10.1097/NRL.0000000000000105


a Barnes-Jewish Hospital, Washington University, School of Medicine, St Louis, MO, United States
b Becker Medical Library, Washington University, School of Medicine, St Louis, MO, United States
c Department of Medicine, Division of Oncology, Washington University, School of Medicine, St Louis, MO, United States
d Department of Neurology, Washington University, School of Medicine, 660S. Euclid Avenue, St Louis, MO, United States


Abstract
Introduction: There are increasing reports of posterior reversible encephalopathy syndrome (PRES) associated with the use of chemotherapeutic agents. Recognition of PRES is crucial given its reversibility with appropriate supportive management. We report a patient presenting with PRES after treatment with Rituximab, Cyclophosphamide, Hydroxydaunorubicin/Adriamycin, Oncovin/Vincristine, Prednisone (R-CHOP) and intrathecal methotrexate. We also perform a systematic review of the literature on chemotherapy-associated PRES. Case Report: A 72-year-old man with recently diagnosed diffuse large B-cell lymphoma became unresponsive 4 days after initiation of R-CHOP and intrathecal methotrexate. Brain magnetic resonance imaging showed interval development of occipital and temporal fluid attenuation inversion recovery hyperintensities consistent with PRES. The patient's blood pressure was aggressively controlled and he received 5 days of high-dose methylprednisone. He subsequently regained consciousness and his mental status gradually improved. Repeat magnetic resonance imaging showed interval resolution of the bilateral fluid attenuation inversion recovery hyperintensities. Review Summary: We performed a systematic review of the literature and included a total of 70 unique cases involving chemotherapyassociated PRES. Platinum-containing drugs, Cyclophosphamide, Hydroxydaunorubicin/Adriamycin, Oncovin/Vincristine, Prednisone/ R-CHOP regimens, and gemcitabine were the agents most commonly used in patients who developed suspected chemo-associated PRES. Median onset of symptoms occurred 8 days after chemotherapy. Hypertension was the most commonly reported risk factor associated with the development of chemotherapy-associated PRES. In most cases, PRES improved with supportive management alone within 2 weeks. Conclusions: Chemotherapy-associated PRES is an increasingly encountered syndrome. Both neurologists and non-neurologists should be familiar with the most commonly implicated agents, symptoms, risk factors, and clinical course of chemotherapy-associated PRES, given its favorable prognosis with appropriate management. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Author Keywords
chemotherapy;  posterior reversible encephalopathy syndrome;  reversible posterior leukoencephalopathy


Document Type: Article
Source: Scopus

 

28) 

Cui, V.a , Kouliev, T.b 
Isolated oculomotor nerve palsy resulting from acute traumatic tentorial subdural hematoma
(2016) Open Access Emergency Medicine, 8, pp. 97-101. 

DOI: 10.2147/OAEM.S117687


a Washington University School of Medicine, St Louis, MO, United States
b Emergency Department, Beijing United Family Hospital, Beijing, China


Abstract
Acute subdural hematoma (SDH) resulting from head trauma is a potentially life-threatening condition that requires expedient diagnosis and intervention to ensure optimal patient outcomes. Rapidly expanding or large hematomas, elevated intracranial pressure, and associated complications of brain herniation are associated with high mortality rates and poor recovery of neurological function. However, smaller bleeds (clot thickness <10 mm) or hematomas occurring in infrequent locations, such as the tentorium cerebelli, may be difficult to recognize and patients may present with unusual or subtle signs and symptoms, including isolated cranial nerve palsies. Knowledge of neuroanatomy supported by modern neuroimaging can greatly aid in recognition and diagnosis of such lesions. In this report, we present a case of isolated oculomotor nerve palsy resulting from compressive tentorial SDH following blunt head trauma, review the literature concerning similar cases, and make recommendations regarding the diagnosis of SDH in patients presenting with isolated cranial nerve palsies. © 2016 Cui and Kouliev.


Author Keywords
Cerebral herniation;  Head injury;  Intracranial hemorrhage;  Oculomotor;  Palsy;  Subdural hematoma;  Tentorium;  Trauma


Document Type: Article
Source: Scopus

 

29) 

Kronzer, V.L., Avidan, M.S.
Preventing postoperative delirium: all that glisters is not gold
(2016) The Lancet, 388 (10054), pp. 1854-1856. 

DOI: 10.1016/S0140-6736(16)31353-8


Washington University School of Medicine, Department of Anesthesiology, Saint Louis, MO, United States


Document Type: Note
Source: Scopus

 

30) 

Hibbing, M.E.a b , Conover, M.S.a b , Hultgren, S.J.a b 
The unexplored relationship between urinary tract infections and the autonomic nervous system
(2016) Autonomic Neuroscience: Basic and Clinical, 200, pp. 29-34. 

DOI: 10.1016/j.autneu.2015.06.002


a Department of Molecular Microbiology and Microbial Pathogenesis, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Center for Women's Infectious Disease Research, Washington University School of Medicine in St. Louis, St. Louis, MO, United States


Abstract
Urinary tract infections (UTIs), the majority of which are caused by uropathogenic E. coli (UPEC), are extremely common infections that preferentially effect women. Additional complicating factors, such as catheterization, diabetes, and spinal cord injuries can increase the frequency and severity of UTIs. The rise of antimicrobial resistant uropathogens and the ability of this disease to chronically recur make the development of alternative preventative and therapeutic modalities a priority. The major symptoms of UTIs, urgency, frequency, and dysuria, are readouts of the autonomic nervous system (ANS) and the majority of the factors that lead to complicated UTIs have been shown to impact ANS function. This review summarizes the decades’ long efforts to understand the molecular mechanisms of the interactions between UPEC and the host, with a particular focus on the recent findings revealing the molecular, bacteriological, immunological and epidemiological complexity of pathogenesis. Additionally, we describe the progress that has been made in: i) generating vaccines and anti-virulence compounds that prevent and/or treat UTI by blocking bacterial adherence to urinary tract tissue and; and ii) elucidating the mechanism by which anti-inflammatories are able to alleviate symptoms and improve disease prognosis. Finally, the potential relationships between the ANS and UTI are considered throughout. While these relationships have not been experimentally explored, the known interactions between numerous UTI characteristics (symptoms, complicating factors, and inflammation) and ANS function suggest that UTIs are directly impacting ANS stimulation and that ANS (dys)function may alter UTI prognosis. © 2015 Elsevier B.V.


Author Keywords
Autonomic nervous system;  Complicated UTI;  Therapeutics;  Urinary tract infection;  Uropathogenic E. coli


Document Type: Review
Source: Scopus

 

31) 

Womer, F.Y.a , Tang, Y.c d , Harms, M.P.a , Bai, C.b d , Chang, M.b d , Jiang, X.b d , Wei, S.b d , Wang, F.b c d , Barch, D.M.a e f 
Sexual dimorphism of the cerebellar vermis in schizophrenia
(2016) Schizophrenia Research, 176 (2-3), pp. 164-170. 

DOI: 10.1016/j.schres.2016.06.028


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
c Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
d The Brain Imaging Center, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
e Department of Radiology, Washington University, St. Louis, MO, United States
f Department of Psychology, Washington University, St. Louis, MO, United States


Abstract
Converging lines of evidence implicate structural and functional abnormalities in the cerebellum in schizophrenia (SCZ). The cerebellar vermis is of particular interest given its association with clinical symptoms and cognitive deficits in SCZ and its known connections with cortical regions such as the prefrontal cortex. Prior neuroimaging studies have shown structural and functional abnormalities in the vermis in SCZ. In this study, we examined the cerebellar vermis in 50 individuals with SCZ and 54 healthy controls (HC) using a quantitative volumetric approach. All participants underwent high-resolution structural magnetic resonance imaging (MRI). The vermis was manually traced for each participant, and vermis volumes were computed using semiautomated methods. Volumes for total vermis and vermis subregions (anterior and posterior vermis) were analyzed in the SCZ and HC groups. Significant diagnosis-by-sex interaction effects were found in total vermis and vermis subregion analyses. These effects appeared to be driven by significantly decreased posterior vermis volumes in males with SCZ. Exploratory analyses did not reveal significant effects of clinical variables (FEP status, illness duration, and BPRS total score and subscores) on vermis volumes. The findings herein highlight the presence of neural sex differences in SCZ and the need for considering sex-related factors in studying the disorder. © 2016 Elsevier B.V.


Author Keywords
Cerebellar vermis;  Schizophrenia;  Sex difference;  Structural MRI


Document Type: Article
Source: Scopus

 

32) 

Culbreth, A.J.a , Westbrook, A.a , Xu, Z.c , Barch, D.M.a b , Waltz, J.A.c 
Intact Ventral Striatal Prediction Error Signaling in Medicated Schizophrenia Patients
(2016) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 1 (5), pp. 474-483. Cited 1 time.

DOI: 10.1016/j.bpsc.2016.07.007


a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri, United States
b Department of Psychiatry & Radiology (DMB), Washington University in St. Louis, St. Louis, Missouri, United States
c Department of Psychiatry and Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, United States


Abstract
Background Midbrain dopaminergic neurons code a computational quantity, reward prediction error (RPE), which has been causally related to learning. Recently, this insight has been leveraged to link phenomenological and biological levels of understanding in psychiatric disorders, such as schizophrenia. However, results have been mixed, possibly due to small sample sizes. Here we present results from two studies with relatively large sample sizes to assess ventral striatum (VS) RPE in schizophrenia. Methods In the current study we analyzed data from two independent studies, involving a total of 87 chronic medicated schizophrenia patients and 61 control subjects. Subjects completed a probabilistic reinforcement-learning task in conjunction with functional magnetic resonance imaging scanning. We fit each participant's choice behavior to a Q-learning model and derived trialwise RPEs. We then modeled blood oxygen level–dependent (BOLD) signal data with parametric regressor functions using these values to determine whether patient and control groups differed in prediction error–related BOLD signal modulations. Results Both groups demonstrated robust VS RPE BOLD activations. Interestingly, these BOLD activation patterns did not differ between groups in either study. This was true when we included all participants in the analysis, as well as when we excluded participants whose data was not sufficiently fit by the models. Conclusions These data demonstrate the utility of computational methods in isolating or testing underlying mechanisms of interest in psychiatric disorders. Importantly, similar VS RPE signal encoding across groups suggests that this mechanism does not drive task deficits in these patients. Deficits may instead stem from aberrant prefrontal or parietal circuits associated with maintenance and selection of goal-relevant information. © 2016 Society of Biological Psychiatry


Author Keywords
Computational psychiatry;  fMRI;  Prediction error;  Reward processing;  Schizophrenia;  Ventral striatum


Document Type: Article
Source: Scopus

 

33) 

Johnsen, S.a , Gagnon, Y.L.b , Marshall, N.J.b , Cronin, T.W.c , Gruev, V.d , Powell, S.d 
Polarization vision seldom increases the sighting distance of silvery fish
(2016) Current Biology, 26 (16), pp. R752-R754. 

DOI: 10.1016/j.cub.2016.07.030


a Biology Department, Duke University, Durham, NC, United States
b Queensland Brain Institute, University of Queensland, St. Lucia, QLD, Australia
c Department of Biological Sciences, University of Maryland, Baltimore, MD, United States
d Department of Computer Science and Engineering, Washington University, St. Louis, MO, United States


Abstract
Although the function of polarization vision, the ability to discern the polarization characteristics of light, is well established in many terrestrial and benthic species, its purpose in pelagic species (squid and certain fish and crustaceans) is poorly understood [1]. A long-held hypothesis is that polarization vision in open water is used to break the mirror camouflage of silvery fish, as biological mirrors can change the polarization of reflected light [2,3]. Although, the addition of polarization information may increase the conspicuousness of silvery fish at close range, direct evidence that silvery fish — or indeed any pelagic animal — are visible at longer distances using polarization vision rather than using radiance (i.e. brightness) vision is lacking. Here we show, using in situ polarization imagery and a new visual detection model, that polarization vision does not in fact appear to allow viewers to see silvery fish at greater distances. © 2016 Elsevier Ltd


Document Type: Letter
Source: Scopus

 

34) 

Weaver, M., Griffey, R.T.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis as an Unusual Cause of Altered Mental Status in the Emergency Department
(2016) Journal of Emergency Medicine, 51 (2), pp. 136-139. 

DOI: 10.1016/j.jemermed.2016.05.003


Barnes-Jewish Hospital, Washington University School of Medicine, Saint Louis, Missouri, United States


Abstract
Background Anti-N-methyl-D-aspartate (NMDA) receptor autoimmune encephalitis is a newly identified form of encephalitis whose incidence is on the rise. Awareness of this condition and symptom recognition are key to early diagnosis and prompt treatment, which may alter the course of the disease. Case Report A 35-year-old woman presented to our Emergency Department (ED) with lethargy, bizarre behavior, agitation, confusion, memory deficits, and word-finding difficulties. Her symptoms and evaluation were potentially consistent with a primary psychiatric disorder, but the absence of frank psychosis and presence of neurologic features related to memory and cognition prompted other considerations. In the ED we performed a lumbar puncture, and in addition to routine studies, ordered anti-NMDAR antibody screening. The screening studies returned positive, leading to treatment with glucocorticoids and intravenous immune globulin and resulting in improvement to near baseline function. Why Should an Emergency Physician Be Aware of This? Although anti-NMDAR encephalitis is relatively uncommon, reports of this previously unrecognized condition are increasing, with an unclear true incidence of disease. Emergency providers should consider this diagnosis in their differential for patients presenting with new neuropsychiatric symptoms, particularly in young women. Prompt treatment leads to near complete neurologic recovery in 75% of patients, whereas delays in diagnosis and treatment may be associated with worse outcomes including death. © 2016 Elsevier Inc.


Author Keywords
autoimmune;  encephalitis;  NMDA;  NMDA encephalitis;  psychosis


Document Type: Article
Source: Scopus

 

35) 

Kun-Rodrigues, C.a , Ross, O.A.b , Orme, T.a , Shepherd, C.c d , Parkkinen, L.e , Darwent, L.a , Hernandez, D.f , Ansorge, O.e , Clark, L.N.g h , Honig, L.S.g h , Marder, K.g h , Lemstra, A.i , Scheltens, P.i , van der Flier, W.i , Louwersheimer, E.i , Holstege, H.i , Rogaeva, E.j , St. George-Hyslop, P.j , Londos, E.k , Zetterberg, H.l , Barber, I.m , Braae, A.m , Brown, K.m , Morgan, K.m , Maetzler, W.n o , Berg, D.n o , Troakes, C.p , Al-Sarraj, S.p , Lashley, T.q , Holton, J.q , Compta, Y.r , Van Deerlin, V.s , Trojanowski, J.Q.s , Serrano, G.E.t , Beach, T.G.t , Clarimon, J.u , Lleó, A.u , Morenas-Rodríguez, E.u , Lesage, S.v w , Galasko, D.x y , Masliah, E.x y , Santana, I.z , Diez, M.aa ab , Pastor, P.aa ab , Tienari, P.J.ac , Myllykangas, L.ad , Oinas, M.ae , Revesz, T.q , Lees, A.q , Boeve, B.F.af , Petersen, R.C.af , Ferman, T.J.ag ah , Escott-Price, V.ai , Graff-Radford, N.aj , Cairns, N.J.ak , Morris, J.C.ak , Stone, D.J.al , Pickering-Brown, S.am , Mann, D.am , Dickson, D.W.b , Halliday, G.M.c d , Singleton, A.f , Guerreiro, R.an , Bras, J.an 
Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies
(2016) Neurobiology of Aging, . Article in Press. 

DOI: 10.1016/j.neurobiolaging.2016.08.023


a Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
b Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
c Neuroscience Research Australia, Sydney, Australia
d School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia
e Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK
f Laboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, MD, USA
g Taub Institute for Alzheimer Disease and the Aging Brain, Columbia University, New York, NY, USA
h Department of Pathology and Cell Biology, Columbia University, New York, NY, USA
i Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands
j Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
k Clinical Memory Research Unit, Institution of Clinical Sciences Malmö, Lund University, Lund, Sweden
l Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
m Translation Cell Sciences-Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK
n Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, Tuebingen, Germany
o Department of Neurology, Christian-Albrechts University of Kiel, Kiel, Germany
p Department of Basic and Clinical Neuroscience and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
q Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
r Movement Disorders Unit, Neurology Service, Clinical Neuroscience Institute (ICN), Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain
s Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
t Banner Sun Health Research Institute, Sun City, AZ, USA
u Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universidad Autònoma de Barcelona, Barcelona, Catalonia, Spain
v Sorbonne Université, Université Pierre et Marie Curie-Paris 06, Inserm, Centre National de la Reserche Scientifique, Institute du Cerveau et de la Moelle épinière, Paris, France
w Assistance Publique Hôpitaux de Paris, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, Paris, France
x Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
y Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA
z Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
aa Memory Unit, Department of Neurology, University Hospital Mútua de Terrassa, and Foundation Mútua de Terrassa, Barcelona, Spain
ab Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
ac Molecular Neurology, Research Programs Unit, University of Helsinki, Department of Neurology, Helsinki University Hospital, Helsinki, Finland
ad Department of Pathology, University of Helsinki, Helsinki, Finland and HUSLAB
ae Department of Neuropathology and Neurosurgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
af Neurology Department, Mayo Clinic, Rochester, MN, USA
ag Department of Psychiatry, Mayo Clinic, Jacksonville, FL, USA
ah Department of Psychology, Mayo Clinic, Jacksonville, FL, USA
ai MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK
aj Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
ak Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
al Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA
am Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
an Department of Medical Sciences and Institute of Biomedicine-iBiMED, University of Aveiro, Aveiro, Portugal


Abstract
. C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of . C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of . C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that . C9orf72 repeat expansions are not causally associated with DLB. © 2016 Elsevier Inc.


Author Keywords
C9orf72;  Dementia with Lewy bodies (DLB);  Genetic screen


Document Type: Article in Press
Source: Scopus

 

36) 

Washington, N.
Culturally unbound cross-cultural cognitive diversity and the science of psychopathology
(2016) Philosophy, Psychiatry and Psychology, 23 (2), art. no. 638292, pp. 165-179. 

DOI: 10.1353/ppp.2016.0014


Washington University in St. Louis, Moral Psychology Research Group, United States


Abstract
In this paper, I consider how human psychological variation should affect methodology in two-stage psychiatric research. I examine recent empirical evidence and develop what I call the Cross-Cultural Diversity picture of the human mind, according to which variation in the underlying causal structure of the human mind implies variation in mental illnesses. I then examine the implications of the Cross-Cultural Diversity view for a discipline that tries to separate the descriptive from the evaluative in taxonomization of mental disorders, by examining one methodological proposal given by philosopher Dominic Murphy in his book Psychiatry in the Scientific Image. I argue that, even in an idealized case, Murphy’s methodology is hindered by its reliance on a conception of ‘normal human nature,’ and thus does not adequately accommodate cognitive diversity. Next I sketch a promising way to revise Murphy’s proposed methodology, by examining Grant Ramsey’s recent work on human nature and his Life-history Trait Cluster view. I end with some notes on how these considerations are beginning to shape inquiry in the form of the Research Domain Criteria project. © 2016 by The Johns Hopkins University Press.


Author Keywords
Diagnosis;  Disorder;  Human nature;  Methodology;  Psychopathology;  RDoC


Document Type: Article
Source: Scopus

 

37) 

Dhand, A.a , Dalton, A.E.b , Luke, D.A.c , Gage, B.F.d , Lee, J.-M.e 
Accuracy of Wearable Cameras to Track Social Interactions in Stroke Survivors
(2016) Journal of Stroke and Cerebrovascular Diseases, . Article in Press. 

DOI: 10.1016/j.jstrokecerebrovasdis.2016.08.004


a Department of Neurology, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts
b Department of Computer Science, Dartmouth College, Hanover, New Hampshire
c George Warren Brown School of Social Work, Washington University in St. Louis, St. Louis, Missouri
d Division of General Medical Sciences, Washington University School of Medicine, St. Louis, Missouri
e Department of Neurology, Washington University School of Medicine, St. Louis, Missouri


Abstract
Background: Social isolation after a stroke is related to poor outcomes. However, a full study of social networks on stroke outcomes is limited by the current metrics available. Typical measures of social networks rely on self-report, which is vulnerable to response bias and measurement error. We aimed to test the accuracy of an objective measure-wearable cameras-to capture face-to-face social interactions in stroke survivors. If accurate and usable in real-world settings, this technology would allow improved examination of social factors on stroke outcomes. Methods: In this prospective study, 10 stroke survivors each wore 2 wearable cameras: Autographer (OMG Life Limited, Oxford, United Kingdom) and Narrative Clip (Narrative, Linköping, Sweden). Each camera automatically took a picture every 20-30 seconds. Patients mingled with healthy controls for 5 minutes of 1-on-1 interactions followed by 5 minutes of no interaction for 2 hours. After the event, 2 blinded judges assessed whether photograph sequences identified interactions or noninteractions. Diagnostic accuracy statistics were calculated. Results: A total of 8776 photographs were taken and adjudicated. In distinguishing interactions, the Autographer's sensitivity was 1.00 and specificity was .98. The Narrative Clip's sensitivity was .58 and specificity was 1.00. The receiver operating characteristic curves of the 2 devices were statistically different (Z = 8.26, . P < .001). Conclusions: Wearable cameras can accurately detect social interactions of stroke survivors. Likely because of its large field of view, the Autographer was more sensitive than the Narrative Clip for this purpose. © 2016 National Stroke Association.


Author Keywords
Computers;  Handheld;  Health behavior;  Interpersonal relations;  Photography/instrumentation;  Rehabilitation;  Stroke


Document Type: Article in Press
Source: Scopus

 

38) 

Cobia, D.J.a , Smith, M.J.a , Salinas, I.a , Ng, C.c , Gado, M.d , Csernansky, J.G.a , Wang, L.a b 
Progressive deterioration of thalamic nuclei relates to cortical network decline in schizophrenia
(2016) Schizophrenia Research, . Article in Press. 

DOI: 10.1016/j.schres.2016.08.003


a Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 446 E. Ontario, Suite 7-100, Chicago, IL 60611, USA
b Department of Radiology, Northwestern University Feinberg School of Medicine, 446 E. Ontario, Suite 7-100, Chicago, IL 60611, USA
c Virginia Commonwealth University, Chesterfield Family Practice Center, 2500 Pocoshock Place, Suite 202, Richmond, VA 23235, USA
d Department of Radiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA


Abstract
Thalamic abnormalities are considered part of the complex pathophysiology of schizophrenia, particularly the involvement of specific thalamic nuclei. The goals of this study were to: introduce a novel atlas-based parcellation scheme for defining various thalamic nuclei; compare their integrity in a schizophrenia sample against healthy individuals at baseline and follow-up time points, as well as rates of change over time; examine relationships between the nuclei and abnormalities in known connected cortical regions; and finally, to determine if schizophrenia-related thalamic nuclei changes relate to cognitive functioning and clinical symptoms. Subjects were from a larger longitudinal 2-year follow-up study, schizophrenia (n. =20) and healthy individuals (n. =20) were group-matched for age, gender, and recent-alcohol use. We used high-dimensional brain mapping to obtain thalamic morphology, and applied a novel atlas-based method for delineating anterior, mediodorsal, and pulvinar nuclei. Results from cross sectional GLMs revealed group differences in bilateral mediodorsal and anterior nuclei, while longitudinal models revealed significant group-by-time interactions for the mediodorsal and pulvinar nuclei. Cortical correlations were the strongest for the pulvinar in frontal, temporal and parietal regions, followed by the mediodorsal nucleus in frontal regions, but none in the anterior nucleus. Thalamic measures did not correlate with cognitive and clinical scores at any time point or longitudinally. Overall, findings revealed a pattern of persistent progressive abnormalities in thalamic nuclei that relate to advancing cortical decline in schizophrenia, but not with measures of behavior. © 2016 Elsevier B.V.


Author Keywords
Cognition;  Cortex;  Longitudinal;  Nuclei;  Schizophrenia;  Thalamus


Document Type: Article in Press
Source: Scopus

 

39) 

Miller, J.B.a b , Merck, L.H.c , Wira, C.R.e , Meurer, W.J.f , Schrock, J.W.g , Nomura, J.T.h , Siket, M.S.d , Madsen, T.E.d , Wright, D.W.i , Panagos, P.D.j , Lewandowski, C.a 
The Advanced Reperfusion Era: Implications for Emergency Systems of Ischemic Stroke Care
(2016) Annals of Emergency Medicine, . Article in Press. 

DOI: 10.1016/j.annemergmed.2016.06.042


a Department of Emergency Medicine, Henry Ford Hospital and Wayne State University, Detroit, MI
b Department of Internal Medicine, Henry Ford Hospital and Wayne State University, Detroit, MI
c Department of Emergency Medicine and the Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown University, Providence, RI
d Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, RI
e Department of Emergency Medicine and the Department of Neurology, Yale School of Medicine, New Haven, CT
f Department of Emergency Medicine and the Department of Neurology, University of Michigan, Ann Arbor, MI
g Department of Emergency Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH
h Department of Emergency Medicine and the Department of Neurosciences, Christiana Care Health System, Newark, DE
i Department of Emergency Medicine, Emory University School of Medicine and Grady Memorial Hospital, Atlanta, GA
j Department of Emergency Medicine and the Department of Neurology, Washington University, St Louis, MO


Abstract
Large vessel ischemic stroke is a leading cause of morbidity and mortality throughout the world. Recent advances in endovascular stroke treatment are changing the treatment paradigm for these patients. This concepts article summarizes the time-dependent nature of stroke care and evaluates the recent advancements in endovascular treatment. These advancements have significant implications for out-of-hospital, hospital, and regional systems of stroke care. Emergency medicine clinicians have a central role in implementing these systems that will ensure timely treatment of patients and selection of those who may benefit from endovascular care. © 2016 American College of Emergency Physicians.


Document Type: Article in Press
Source: Scopus

 

 

40) 

Kelly, M.P.a l , Zebala, L.P.a , Kim, H.J.b , Sciubba, D.M.c , Smith, J.S.d , Shaffrey, C.I.d , Bess, S.e , Klineberg, E.f , Mundis, G., Jr.g , Burton, D.h , Hart, R.i , Soroceanu, A.j , Schwab, F.k , Lafage, V.k 
Effectiveness of preoperative autologous blood donation for protection against allogeneic blood exposure in adult spinal deformity surgeries: A propensity-matched cohort analysis
(2016) Journal of Neurosurgery: Spine, 24 (1), pp. 124-130. 

DOI: 10.3171/2015.4.SPINE141329


a Department of Orthopedic Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Box 8233, Saint Louis, MO, United States
b Department of Orthopedic Surgery, Hospital for Special Surgery, New York, NY, United States
c Department of Neurological Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
d Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, VA, United States
e Rocky Mountain Hospital for Children, Denver, CO, United States
f Department of Orthopedic Surgery, University of California, Davis, Sacramento, United States
g San Diego Center for Spinal Disorders, San Diego, CA, United States
h Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, KS, United States
i Department of Orthopedic Surgery, Oregon Health and Science University, Portland, OR, United States
j Department of Surgery, University of Calgary, School of Medicine, Calgary, AB, Canada
k Department of Orthopedic Surgery, New York University, School of Medicine, New York, NY, United States


Abstract
OBJECTIVE: The goal of this study was to examine the effectiveness of preoperative autologous blood donation (PABD) in adult spinal deformity (ASD) surgery. METHODS: Patients undergoing single-stay ASD reconstructions were identified in a multicenter database. Patients were divided into groups according to PABD (either PABD or NoPABD). Propensity weighting was used to create matched cohorts of PABD and NoPABD patients. Allogeneic (ALLO) exposure, autologous (AUTO) wastage (unused AUTO), and complication rates were compared between groups. RESULTS: Four hundred twenty-eight patients were identified as meeting eligibility criteria. Sixty patients were treated with PABD, of whom 50 were matched to 50 patients who were not treated with PABD (NoPABD). Nearly one-third of patients in the PABD group (18/60, 30%) did not receive any autologous transfusion and donated blood was wasted. In 6 of these cases (6/60, 10%), patients received ALLO blood transfusions without AUTO. In 9 cases (9/60, 15%), patients received ALLO and AUTO blood transfusions. Overall rates of transfusion of any type were similar between groups (PABD 70% [42/60], NoPABD 75% [275/368], p = 0.438). Major and minor in-hospital complications were similar between groups (Major PABD 10% [6/60], NoPABD 12% [43/368], p = 0.537; Minor PABD 30% [18/60], NoPABD 24% [87/368], p = 0.499). When controlling for potential confounders, PABD patients were more likely to receive some transfusion (OR 15.1, 95% CI 2.1-106.7). No relationship between PABD and ALLO blood exposure was observed, however, refuting the concept that PABD is protective against ALLO blood exposure. In the matched cohorts, PABD patients were more likely to sustain a major perioperative cardiac complication (PABD 8/50 [16%], NoPABD 1/50 [2%], p = 0.046). No differences in rates of infection or wound-healing complications were observed between cohorts. CONCLUSIONS: Preoperative autologous blood donation was associated with a higher probability of perioperative transfusions of any type in patients with ASD. No protective effect of PABD against ALLO blood exposure was observed, and no risk of perioperative infectious complications was observed in patients exposed to ALLO blood only. The benefit of PABD in patients with ASD remains undefined. ©AANS, 2016.


Author Keywords
Adult spinal deformity;  Allogeneic blood;  Autologous blood;  Complications;  Transfusion


Document Type: Article
Source: Scopus