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Office of Neuroscience Research > Resources and Facilities > WUSTL Neuroscience Publications for the week > Weekly Neuroscience Publications - Archives > WUSTL Neuroscience Publications Archive - February 2015

WUSTL Neuroscience Publications Archive - February 2015

 Scopus weekly report:

February 13

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February 27, 2015

 

Zhang, Y.a , Inder, T.E.b , Neil, J.J.c , Dierker, D.L.d , Alexopoulos, D.e , Anderson, P.J.f , Van Essen, D.C.d
Cortical structural abnormalities in very preterm children at 7years of age
(2015) NeuroImage, 109, pp. 469-479. 

DOI: 10.1016/j.neuroimage.2015.01.005


a Division of Biomedical and Biological Science, Washington University School of MedicineSt Louis, MO, United States
b Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical SchoolBoston, MA, United States
c Department of Neurology, Boston Children's Hospital, Harvard Medical SchoolBoston, MA, United States
d Department of Anatomy and Neurobiology, Washington University School of MedicineSt Louis, MO, United States
e Department of Neurology, Washington University School of MedicineSt Louis, MO, United States
f Clinical Sciences, Murdoch Children's Research InstituteVIC, Australia


Abstract
We analyzed long-lasting alterations in brain morphometry associated with preterm birth using volumetric and surface-based analyses applied to children at age 7. years. Comparison of 24 children born very preterm (VPT) to 24 healthy term-born children revealed reductions in total cortical gray matter volume, white matter volume, cortical surface area and gyrification index. Regional cortical shape abnormalities in VPT children included the following: shallower anterior superior temporal sulci, smaller relative surface area in the inferior sensori-motor cortex and posterior superior temporal cortex, larger relative surface area and a cingulate sulcus that was shorter or more interrupted in medial frontoparietal cortex. These findings indicate a complex pattern of regional vulnerabilities in brain development that may contribute to the diverse and long-lasting neurobehavioral consequences that can occur after very premature birth.


Author Keywords
Cortical surface;  Folding;  MRI;  Relative surface area;  Structural abnormality;  Very preterm;  Volume


Document Type: Article
Source: Scopus




Wood, M.D., Mackinnon, S.E.
Pathways regulating modality-specific axonal regeneration in peripheral nerve
(2015) Experimental Neurology, 265, pp. 171-175. 

DOI: 10.1016/j.expneurol.2015.02.001


Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid AvenueSt. Louis, MO, United States


Abstract
Following peripheral nerve injury, the distal nerve is primed for regenerating axons by generating a permissive environment replete with glial cells, cytokines, and neurotrophic factors to encourage axonal growth. However, increasing evidence demonstrates that regenerating axons within peripheral nerves still encounter axonal-growth inhibitors, such as chondroitin sulfate proteoglycans. Given the generally poor clinical outcomes following peripheral nerve injury and reconstruction, the use of pharmacological therapies to augment axonal regeneration and overcome inhibitory signals has gained considerable interest. Joshi et al. (2014) have provided evidence for preferential or modality-specific (motor versus sensory) axonal growth and regeneration due to inhibitory signaling from Rho-associated kinase (ROCK) pathway regulation. By providing inhibition to the ROCK signaling pathway through Y-27632, they demonstrate that motor neurons regenerating their axons are impacted to a greater extent compared to sensory neurons. In light of this evidence, we briefly review the literature regarding modality-specific axonal regeneration to provide context to their findings. We also describe potential and novel barriers, such as senescent Schwann cells, which provide additional axonal-growth inhibitory factors for future consideration following peripheral nerve injury.


Author Keywords
Axon modality;  Chondroitin sulfate proteoglycan;  Motor neuron;  Nerve regeneration;  Peripheral nerve;  RhoA;  ROCK;  Schwann cell;  Sensory neuron;  Y-27632


Document Type: Note
Source: Scopus




Lucas, J.R.a , Vélez, A.a c , Henry, K.S.b
Habitat-related differences in auditory processing of complex tones and vocal signal properties in four songbirds
(2015) Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology, 16 p. Article in Press. 

DOI: 10.1007/s00359-015-0986-7


a Department of Biological Sciences, Lilly Hall, Purdue University, 915 W. State St.West Lafayette, IN, United States
b Department of Biomedical Engineering, University of Rochester, 601 Elmwood Ave Box 603Rochester, NY, United States
c Department of Biology, Washington University in St. LouisSt. Louis, MO, United States


Abstract
We examined temporal processing of harmonic tone complexes in two woodland species (tufted titmice and white-breasted nuthatches) and two open-habitat species (house sparrows and white-crowned sparrows). Envelope and fine-structure processing were quantified using the envelope following response (EFR) and frequency following response (FFR). We predicted stronger EFRs in the open-habitat species based on broader auditory filters and greater amplitude modulation of vocal signals in this group. We predicted stronger FFRs in woodland species based on narrower auditory filters. As predicted, EFR amplitude was generally greatest in the open habitat species. FFR amplitude, in contrast, was greatest in white-crowned sparrows with no clear difference between habitats. This result cannot be fully explained by species differences in audiogram shape and might instead reflect greater acoustic complexity of songs in the white-crowned sparrow. Finally, we observed stronger FFRs in woodland species when tones were broadcast with the next higher harmonic in the complex. Thus, species such as nuthatches that have songs with strong harmonics may process these sounds using enhanced spectral processing instead of enhanced amplitude-envelope processing. The results suggest coevolution between signal design and temporal processing of complex signals and underscore the need to study auditory processing with a diversity of signals.


Author Keywords
Amplitude envelope;  Audiogram;  Auditory evoked potential;  Hearing;  Phase-locking


Document Type: Article in Press
Source: Scopus




Maloney, S.E.a b , Khangura, E.a b , Dougherty, J.D.a b
The RNA-binding protein Celf6 is highly expressed in diencephalic nuclei and neuromodulatory cell populations of the mouse brain
(2015) Brain Structure and Function, 23 p. Article in Press. 

DOI: 10.1007/s00429-015-1005-z


a Department of Genetics, Washington University School of Medicine, Campus Box 8232, 4566 Scott Ave.St. Louis, MO, United States
b Department of Psychiatry, Washington University School of MedicineSt. Louis, MO, United States


Abstract
The gene CUG-BP, Elav-like factor 6 (CELF6) appears to be important for proper functioning of neurocircuitry responsible for behavioral output. We previously discovered that polymorphisms in or near CELF6 may be associated with autism spectrum disorder (ASD) in humans and that the deletion of this gene in mice results in a partial ASD-like phenotype. Here, to begin to understand which circuits might mediate these behavioral disruptions, we sought to establish in what structures, with what abundance, and at which ages Celf6 protein is present in the mouse brain. Using both a knockout-validated antibody to Celf6 and a novel transgenic mouse line, we characterized Celf6 expression in the mouse brain across development. Celf6 gene products were present early in neurodevelopment and in adulthood. The greatest protein expression was observed in distinct nuclei of the diencephalon and neuromodulatory cell populations of the midbrain and hindbrain, with clear expression in dopaminergic, noradrenergic, histaminergic, serotonergic and cholinergic populations, and a variety of presumptive peptidergic cells of the hypothalamus. These results suggest that disruption of Celf6 expression in hypothalamic nuclei may impact a variety of behaviors downstream of neuropeptide activity, while disruption in neuromodulatory transmitter expressing areas such as the ventral tegmental area, substantia nigra, raphe nuclei and locus coeruleus may have far-reaching influences on overall brain activity.


Author Keywords
Celf6;  Development;  Diencephalon;  Immunohistochemistry;  Neuromodulatory;  Protein expression


Document Type: Article in Press
Source: Scopus




Hänggi, D.a , Etminan, N.a , Macdonald, R.L.b , Steiger, H.J.a , Mayer, S.A.c , Aldrich, F.d , Diringer, M.N.e , Hoh, B.L.f , Mocco, J.g , Strange, P.h i , Faleck, H.J.h , Miller, M.h i
NEWTON: Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage
(2015) Neurocritical Care, 11 p. Article in Press. 

DOI: 10.1007/s12028-015-0112-2


a Department of Neurosurgery, Medical Faculty, Heinrich-Heine-University, Moorenstraße 5Düsseldorf, Germany
b Division of Neurosurgery, Department of Surgery, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Research and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of TorontoToronto, Canada
c Institute for Critical Care Medicine, Mount Sinai HospitalNew York, NY, United States
d Neurological Surgery, University of Maryland Medical CenterBaltimore, MD, United States
e Neurological Critical Care, Washington University School of MedicineSt. Louis, MO, United States
f Department of Neurosurgery, University of FloridaGainesville, FL, United States
g Department of Neurological Surgery, Vanderbilt University Medical CenterNashville, TN, United States
h Edge TherapeuticsBerkeley Heights, NJ, United States
i Phase 1 to 4, LLCPrinceton Junction, NJ, United States


Abstract
Background: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. EG-1962 is a sustained-release microparticle formulation of nimodipine that has shown preclinical efficacy when administered intraventricularly or intracisternally to dogs with SAH, without evidence of toxicity at doses in the anticipated therapeutic range. Thus, we propose to administer EG-1962 to humans in order to assess safety and tolerability and determine a dose to investigate efficacy in subsequent clinical studies.

Methods: We describe a Phase 1/2a multicenter, controlled, randomized, open-label, dose escalation study to determine the maximum tolerated dose (MTD) and assess the safety and tolerability of EG-1962 in patients with aSAH. The study will comprise two parts: a dose escalation period (Part 1) to determine the MTD of EG-1962 and a treatment period (Part 2) to assess the safety and tolerability of the selected dose of EG-1962. Patients with a ruptured saccular aneurysm treated by neurosurgical clipping or endovascular coiling will be considered for enrollment. Patients will be randomized to receive either EG-1962 (study drug: nimodipine microparticles) or oral nimodipine in the approved dose regimen (active control) within 60 h of aSAH.

Results: Primary objectives are to determine the MTD and the safety and tolerability of the selected dose of intraventricular EG-1962 as compared to enteral nimodipine. The secondary objective is to determine release and distribution by measuring plasma and CSF concentrations of nimodipine. Exploratory objectives are to determine the incidence of delayed cerebral infarction on computed tomography, clinical features of delayed cerebral ischemia, angiographic vasospasm, and incidence of rescue therapy and clinical outcome. Clinical outcome will be determined at 90 days after aSAH using the extended Glasgow outcome scale, modified Rankin scale, Montreal cognitive assessment, telephone interview of cognitive status, and Barthel index.

Conclusion: Here, we describe a Phase 1/2a multicenter, controlled, randomized, open-label, dose escalation study to determine the MTD and assess the safety and tolerability of EG-1962 in patients with aSAH.


Author Keywords
Cerebral aneurysm;  Clinical trial;  Delayed cerebral ischemia;  Nimodipine;  Subarachnoid hemorrhage;  Sustained drug release


Document Type: Article in Press
Source: Scopus




Lee, A.J.a , Bosch, R.J.a , Evans, S.R.a , Wu, K.a , Harrison, T.b , Grant, P.c , Clifford, D.B.d
Patterns of peripheral neuropathy in ART-naïve patients initiating modern ART regimen
(2015) Journal of NeuroVirology, 9 p. Article in Press. 

DOI: 10.1007/s13365-015-0327-1


a Center for Biostatistics in AIDS Research, Department of Biostatistics, FXB 604B, Harvard School of Public Health, 651 Huntington AvenueBoston, MA, United States
b Department of Neurology, Emory University School of Medicine, Grady Memorial HospitalAtlanta, GA, United States
c Department of Medicine-Infectious Disease, Stanford School of MedicineStanford, CA, United States
d Department of Neurology, Washington UniversitySaint Louis, Mo, United States


Abstract
The purpose of this study was to evaluate associations of pre-ART CD4 with peripheral neuropathy (PN) and estimate the prevalence of PN in HIV-positive patients starting modern combination antiretroviral therapy (cART) regimens. ART-naïve subjects initiating cART were followed longitudinally and screened for signs/symptoms of PN. Lower pre-ART CD4 count was associated with post-ART PN. After 7 years (n = 117), the prevalence (95 % CI) of PN and SPN were 31 % (23, 40 %) and 5 % (2, 11 %) with pre-ART CD4 count >250 copies/μL. PN continues to be identified in HIV-infected individuals on modern cART by targeted assessment but is generally without symptoms.


Author Keywords
Higher pre-ART CD4 count;  HIV;  Modern non-neurotoxic ART;  Peripheral neuropathy;  Risk factors;  Symptomatic peripheral neuropathy


Document Type: Article in Press
Source: Scopus




Leong, S.L.a b g , Hinds, M.G.b c , Connor, A.R.a b , Smith, D.P.d , Illes-Toth, E.d i , Pham, C.L.L.a b h , Barnham, K.J.b e f , Cappai, R.a b
The N-terminal residues 43 to 60 form the interface for dopamine mediated α-synuclein dimerisation
(2015) PLoS ONE, 10 (2), art. no. e0116497, . 

DOI: 10.1371/journal.pone.0116497


a Department of Pathology, University of MelbourneParkville, VIC, Australia
b Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, ParkvilleMelbourne, VIC, Australia
c School of Chemistry, University of Melbourne, ParkvilleMelbourne, VIC, Australia
d Biomedical Research Centre, Sheffield Hallam UniversitySheffield, United Kingdom
e Florey Institute of Neuroscience and Mental Health, University of Melbourne, ParkvilleMelbourne, VIC, Australia
f Department of Pharmacology, University of Melbourne, ParkvilleMelbourne, VIC, Australia
g Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Swann Building, Mayfield RoadEdinburgh, United Kingdom
h Discipline of Pharmacology, School of Medical Sciences, University of Sydney, D06Sydney, NSW, Australia
i Washington University in St. Louis, School of Engineering and Applied Science, Campus Box 1097, One Brookings DriveSt. Louis, MO, United States


Abstract
α-synuclein (α-syn) is a major component of the intracellular inclusions called Lewy bodies, which are a key pathological feature in the brains of Parkinson's disease patients. The neurotransmitter dopamine (DA) inhibits the fibrillisation of α-syn into amyloid, and promotes α-syn aggregation into SDS-stable soluble oligomers. While this inhibition of amyloid formation requires the oxidation of both DA and the methionines in α-syn, the molecular basis for these processes is still unclear. This study sought to define the protein sequences required for the generation of oligomers. We tested N- (α-syn residues 43-140) and C-terminally (1-95) truncated α-syn, and found that similar to full-length protein both truncated species formed soluble DA: α-syn oligomers, albeit 1-95 had a different profile. Using nuclear magnetic resonance (NMR), and the N-terminally truncated α-syn 43-140 protein, we analysed the structural characteristics of the DA:α-syn 43-140 dimer and α-syn 43-140 monomer and found the dimerisation interface encompassed residues 43 to 60. Narrowing the interface to this small region will help define the mechanism by which DA mediates the formation of SDS-stable soluble DA:α-syn oligomers.


Document Type: Article
Source: Scopus




Westbrook, A., Braver, T.S.
Cognitive effort: A neuroeconomic approach
(2015) Cognitive, Affective and Behavioral Neuroscience, 21 p. Article in Press. 

DOI: 10.3758/s13415-015-0334-y


Department of Psychology, Washington University in Saint LouisSaint Louis, MO, United States


Abstract
Cognitive effort has been implicated in numerous theories regarding normal and aberrant behavior and the physiological response to engagement with demanding tasks. Yet, despite broad interest, no unifying, operational definition of cognitive effort itself has been proposed. Here, we argue that the most intuitive and epistemologically valuable treatment is in terms of effort-based decision-making, and advocate a neuroeconomics-focused research strategy. We first outline psychological and neuroscientific theories of cognitive effort. Then we describe the benefits of a neuroeconomic research strategy, highlighting how it affords greater inferential traction than do traditional markers of cognitive effort, including self-reports and physiologic markers of autonomic arousal. Finally, we sketch a future series of studies that can leverage the full potential of the neuroeconomic approach toward understanding the cognitive and neural mechanisms that give rise to phenomenal, subjective cognitive effort.


Author Keywords
Cognitive control;  Decision-making;  Dopamine;  Motivation;  Working memory


Document Type: Article in Press
Source: Scopus




Piccirillo, J.F., Hardin, F.M., Nicklaus, J., Kallogjeri, D., Wilson, M., Ma, C.X., Coalson, R.S., Shimony, J., Schlaggar, B.L.
Cognitive Impairment after Chemotherapy Related to Atypical Network Architecture for Executive Control
(2015) Oncology (Switzerland), . Article in Press. 

DOI: 10.1159/000370117


Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, St. Louis, Mo., USA


Abstract
Objectives: A common complaint of cancer patients is the experience of cognitive difficulty during and after chemotherapy. We hypothesized that cognitive impairment may result from dysfunction in large-scale brain networks, particularly those involved in attentional control. Methods: Using a case-control design, this study includes women with a history of invasive ductal or lobular triple-negative breast cancer who completed standard adjuvant chemotherapy within 2 years of study entry. Women who reported cognitive impairment by the Global Rating of Cognition question were considered to be cases (n = 15). Women who reported no cognitive impairment were considered to be controls (n = 13). All enrolled participants were eligible for MRI investigation and underwent resting-state functional connectivity MRI. Results: Women who self-reported cognitive impairment were found to have disrupted resting-state functional connectivity, as measured by MRI, when compared to women who did not self-report cognitive impairment. These findings suggest that some women may be more sensitive to the standard treatments for breast cancer and that this increased sensitivity may result in functional connectivity alterations in the brain networks supporting attention and executive function. Conclusions: Neuroimaging analyses confirmed self-reported cognitive deficits in women with breast cancer treated with chemotherapy. © 2015 S. Karger AG, Basel


Document Type: Article in Press
Source: Scopus




Brody, D.L.a , Benetatos, J.a , Bennett, R.E.a b , Klemenhagen, K.C.a c , Mac Donald, C.L.a d
The pathophysiology of repetitive concussive traumatic brain injury in experimental models; new developments and open questions
(2015) Molecular and Cellular Neuroscience, . Article in Press. 

DOI: 10.1016/j.mcn.2015.02.005


a Department of Neurology, Washington University School of Medicine and Hope Center for Neurological Disorders, St Louis, MO, USA
b Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
c Department of Psychiatry, Columbia University and Research Foundation for Mental Health, New York State Psychiatric Institute, New York, NY, USA
d Department of Neurosurgery, University of Washington, Seattle, WA, USA


Abstract
In recent years, there has been an increasing interest in the pathophysiology of repetitive concussive traumatic brain injury (rcTBI) in large part due to the association with dramatic cases of progressive neurological deterioration in professional athletes, military personnel, and others. However, our understanding of the pathophysiology of rcTBI is less advanced than for more severe brain injuries. Most prominently, the mechanisms underlying traumatic axonal injury, microglial activation, amyloid-beta accumulation, and progressive tau pathology are not yet known. In addition, the role of injury to dendritic spine cytoskeletal structures, vascular reactivity impairments, and microthrombi are intriguing and subjects of ongoing inquiry. Methods for quantitative analysis of axonal injury, dendritic injury, and synaptic loss need to be refined for the field to move forward in a rigorous fashion. We and others are attempting to develop translational approaches to assess these specific pathophysiological events in both animals and humans to facilitate clinically relevant pharmacodynamic assessments of candidate therapeutics. In this article, we review and discuss several of the recent experimental results from our lab and others. We include new initial data describing the difficulty in modeling progressive tau pathology in experimental rcTBI, and results demonstrating that sertraline can alleviate social interaction deficits and depressive-like behaviors following experimental rcTBI plus foot shock stress. Furthermore, we propose a discrete set of open, experimentally tractable questions that may serve as a framework for future investigations. In addition, we also raise several important questions that are less experimentally tractable at this time, in hopes that they may stimulate future methodological developments to address them.This article is part of a Special Issue entitled "Traumatic Brain Injury".


Author Keywords
Amyloid-beta;  Concussion;  Depression;  Microglia;  Mouse;  Sertraline;  Social behavior;  Tau;  Traumatic axonal injury;  Traumatic brain injury


Document Type: Article in Press
Source: Scopus




Bittel, D.C.a , Bittel, A.J.a , Tuttle, L.J.b , Hastings, M.K.a , Commean, P.K.a , Mueller, M.J.a , Cade, W.T.a , Sinacore, D.R.a
Adipose tissue content, muscle performance and physical function in obese adults with type 2 diabetes mellitus and peripheral neuropathy
(2015) Journal of Diabetes and its Complications, 29 (2), pp. 250-257. 

DOI: 10.1016/j.jdiacomp.2014.11.003


a Program in Physical Therapy, Washington University School of Medicine, 4444 Forest Park AveSt Louis, MO, United States
b Doctor of Physical Therapy Program, School of Exercise and Nutritional Sciences, San Diego State University, 5500 Campanile DrSan Diego, CA, United States


Abstract
Aims To determine leg intermuscular (IMAT) and subcutaneous (SQAT) adipose tissue and their relationships with muscle performance and function in obese adults with and without type 2 diabetes and peripheral neuropathy (T2DMPN). Methods Seventy-nine age-matched obese adults were studied, 13 T2DM, 54 T2DMPN, and 24 obese controls. Leg fat (%IMAT, %SQAT) volumes were quantified using MRI. Ankle plantar flexion (PF) torque and power were assessed with isokinetic dynamometry. Physical function was assessed with 9-item Physical Performance Test (PPT), 6-minute walk distance, single-limb balance, and time to ascend 10 stairs. One-way ANOVAs determined group differences, and multiple regression predicted PPT score from disease status, % IMAT, and PF power. Results T2DMPN participants had 37% greater IMAT volumes and 15% lower SQAT volumes than controls (p =. 01). T2DMPN and T2DM showed reduced PF torque and power compared to controls. T2DMPN participants had lower PPT score, 6-minute walk, single-limb balance, and stair climbing than controls (all p <.05). %IMAT volume correlated inversely, and %SQAT correlated directly, with PPT. Leg %IMAT and disease status predicted 49% of PPT score. Conclusions T2DMPN may represent a shift in adipose tissue accumulation from SQAT to IMAT depots, which is inversely associated with muscle performance and physical function.


Author Keywords
Adipose tissue;  Diabetes;  Muscle;  Neuropathy;  Physical function


Document Type: Article
Source: Scopus




Abdullah, K.N.a , Janardhan, R.a , Hwang, M.a , Williams, C.D.a , Farasatpour, M.a , Margenthaler, J.A.b , Virgo, K.S.c , Johnson, F.E.a d
Adjuvant radiation therapy for breast cancer in patients with schizophrenia
(2015) American Journal of Surgery, 209 (2), pp. 378-384. 

DOI: 10.1016/j.amjsurg.2014.07.004


a Saint Louis University Medical CenterSt. Louis, MO, United States
b Washington University Medical CenterSt. Louis, MO, United States
c American Cancer SocietyAtlanta, GA, United States
d John Cochran Veterans Affairs Medical CenterSt. Louis, MO, United States


Abstract
Background Schizophrenia affects approximately 1% of subjects in all populations studied thus far. We sought to evaluate how patients with schizophrenia who are later diagnosed with breast cancer fare when adjuvant radiation therapy (ART) is clinically indicated. Methods We searched patient treatment file, the national inpatient computer database of the Department of Veterans Affairs, to identify patients with schizophrenia who subsequently developed breast cancer. Results Forty patients had schizophrenia, who later developed breast cancer and were candidates for ART, according to well-established guidelines. Of the 40 patients who were considered candidates for ART, we found data about the decision to offer ART in 35; only 22 (63%) were offered ART and 5 of those 22 (23%) refused it. Conclusions Patients with schizophrenia and breast cancer often do not understand the nature of their illnesses well. They often do not comply with recommended standard therapies such as ART. Treatment strategies that rely on ART are likely to be met with noncompliance. Breast-preserving treatment plans may be impractical. Initial radical surgery without ART may be preferable.


Author Keywords
Adjuvant radiation therapy;  Keywords Breast cancer;  Outcomes;  Schizophrenia


Document Type: Article
Source: Scopus




Sherr, J.a , Tsalikian, E.b , Fox, L.c , Buckingham, B.d , Weinzimer, S.a , Tamborlane, W.a , White, N.e , Arbelaez, A.M.e , Kollman, C.f , Ruedy, K.f , Cheng, P.f , Beck, R.f
Alterations in white matter structure in young children with type 1 diabetes
(2015) Diabetes Technology and Therapeutics, 17, p. S98. 

DOI: 10.1089/dia.2015.1512


a Section of Endocrinology, Department of Pediatrics, Yale University School of MedicineNew Haven, CT, United States
b Stead Family Department of Pediatrics, University of Iowa, Carver College of MedicineIowa City, IA, United States
c Pediatric of Endocrinology, Nemours Children's ClinicJacksonville, United States
d Division of Pediatric, Endocrinology and Diabetes, Stanford UniversityStanford, CA, United States
e Department of Pediatrics, Washington UniversitySt. Louis, MO, United States
f Jaeb Center for Health ResearchTampa, FL, United States


Document Type: Note
Source: Scopus




Barnea-Goraly, N.a , Raman, M.a , Mazaika, P.a , Marzelli, M.a , Hershey, T.b , Weinzimer, S.A.c , Aye, T.d , Buckingham, B.d , Mauras, N.e , White, N.H.f , Fox, L.A.e , Tansey, M.g , Beck, R.W.h , Ruedy, K.J.h , Kollman, C.h , Cheng, P.h , Reiss, A.L.a d i
Alterations in white matter structure in young children with type 1 diabetes
(2015) Diabetes Technology and Therapeutics, 17, pp. S111-S112. 

DOI: 10.1089/dia.2015.1513


a Department of Psychiatry and Behavioral Sciences, Center for Interdisciplinary Brain Sciences ResearchStanford, CA, United States
b Departments of Psychiatry, Neurology, and Radiology, Washington UniversitySt. Louis, MO, United States
c Pediatric Endocrinology, Yale UniversityNew Haven, CT, United States
d Department of Pediatrics, Stanford UniversityStanford, CA, United States
e Pediatric Endocrinology, Nemours Children's ClinicJacksonville, FL, United States
f Departments of Pediatrics and Medicine, Washington University in St. LouisSt. Louis, MO, United States
g Pediatric Endocrinology, University of IowaIowa City, IA, United States
h Jaeb Center for Health ResearchTampa, FL, United States
i Department of Radiology, Stanford UniversityStanford, CA, United States


Document Type: Note
Source: Scopus




Barnea-Goraly, N.a , Raman, M.a , Mazaika, P.a , Marzelli, M.b , Hershey, T.b , Weinzimer, S.A.c , Aye, T.d , Buckingham, B.d , Mauras, N.e , White, N.H.f , Fox, L.A.e , Tansey, M.g , Beck, R.W.h , Ruedy, K.J.h , Kollman, C.h , Cheng, P.h , Reiss, A.L.a d i
Alterations in white matter structure in young children with type 1 diabetes
(2015) Diabetes Technology and Therapeutics, 17, p. S97. 

DOI: 10.1089/dia.2015.1512


a Department of Psychiatry and Behavioral Sciences, Center for Interdisciplinary Brain Sciences ResearchStanford, CA, United States
b Departments of Psychiatry, Neurology, and Radiology, Washington UniversitySt. Louis, MO, United States
c Pediatric Endocrinology, Yale UniversityNew Haven, CT, United States
d Department of Pediatrics, Stanford UniversityStanford, CA, United States
e Pediatric Endocrinology, Nemours Children's ClinicJacksonville, FL, United States
f Departments of Pediatrics and Medicine, Washington UniversitySt. Louis, MO, United States
g Pediatric Endocrinology, University of IowaIowa City, IA, United States
h Jaeb Center for Health ResearchTampa, FL, United States
i Department of Radiology, Stanford UniversityStanford, United States


Document Type: Note
Source: Scopus




Hsu, H.Y.a , Lind, J.T.c , Miller, D.d , Tseng, L.b
Assessment of risk factors for oxacillin-resistant ocular flora in eyes having cataract surgery
(2015) Journal of Cataract and Refractive Surgery, 41 (2), pp. 387-392. 

DOI: 10.1016/j.jcrs.2014.05.050


a Doheny Eye Center UCLA, Department of Ophthalmology, David Geffen School of Medicine at UCLALos Angeles, United States
b Department of Ophthalmology, Permanente Medical Group, Inc.Fresno, CA, United States
c Department of Ophthalmology and Visual Sciences, Washington University in Saint Louis School of MedicineSaint Louis, MO, United States
d Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of MedicineMiami, FL, United States


Abstract
Purpose To assess the risk factors for eyes of cataract surgery patients harboring oxacillin-resistant Staphylococcus species on the ocular surface. Setting Ambulatory surgical center, Saint Louis University, Saint Louis, Missouri, USA. Design Prospective in vitro laboratory study of a patient cohort. Methods Conjunctival cultures were obtained on the day of surgery from eyes scheduled for cataract surgery. Patients answered a questionnaire about risk factors that might lead to having oxacillin-resistant Staphylococcus organisms in their eyes. The factors tested were age, sex, race, recent systemic and topical antibiotic usage, recent hospitalization, and exposure to healthcare and institutional settings. Logistic regression analysis was performed. Results Of the 183 eyes cultured, 128 (70.0%) tested positive for Staphylococcus organisms, of which 70 (54.7%) were oxacillin-resistant. Only recent antibiotic usage was statistically significantly associated with the presence of oxacillin-resistant organisms (odds ratio, 8.2; 95% confidence interval, 2.2-30.5; P=.002). The other risk factors were not statistically significantly associated: age (P=.06), sex (P=.33), race (P=.34), recent hospitalization (P=.94), and exposure to healthcare and institutional settings (P=.10). Conclusions Although the nonophthalmic literature has reported various risk factors for the harboring of oxacillin-resistant organisms, in the eyes in this study, only antibiotic usage within 30 days preoperatively was significantly associated with the colonization of oxacillin-resistant organisms on the ocular surface. This finding is important to ophthalmic surgeons when considering perioperative antibiotic prophylaxis. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.


Document Type: Article
Source: Scopus




Finger, S.a , Zeitler, W.b
Benjamin Franklin and his glass armonica: From music as therapeutic to pathological
(2015) Progress in Brain Research, 216, pp. 93-125. 

DOI: 10.1016/bs.pbr.2014.11.005


a Department of Psychology, Washington UniversitySt. Louis, MO, United States
b San Bernardino, CA, United States


Abstract
In 1762, Benjamin Franklin, then in London, wrote a letter to a colleague in Italy describing his latest invention, a musical instrument he called the "armonica," which was based on how rubbing a wet finger on the rims of wine glasses could produce musical tones. In contrast to earlier sets of wine glasses that could be tapped or rubbed, Franklin put a set of glass bowls differing in size on a horizontal rod turned by a food treadle, thus freeing both hands for touching the rotating glasses and allowing musicians to play more than two glasses at a time, as well as eliminating the nuisance of water tuning. Franklin played his instrument for pleasure, to manipulate the "passions" (emotions) and to treat melancholia. Nevertheless, late in his lifetime some individuals began to view glass armonica music differently, alleging it could cause nerve damage and mental problems. Here, we look at how Franklin used his glass armonica to manipulate the passions and examine what he must have thought about it supposedly causing health problems. We present Franklin as an empiricist, whose focus was more on results than theories; as an astute student of human behavior understanding the power of charms and other "nonsense"; and as a man of medicine living in an era when much was being attributed to the nerves, even though next to nothing was really known about the underlying nerve force.


Author Keywords
Charms;  Emotions;  Franklin (Benjamin);  Glass armonica;  Glass music;  History of medicine;  History of music;  Music therapy;  Musical glasses;  Nerve damage;  Passions;  Psychotherapy


Document Type: Article
Source: Scopus




Siegfried, C.J.a , Shui, Y.-B.a , Bai, F.a , Beebe, D.C.a b
Central corneal thickness correlates with oxygen levels in the human anterior chamber angle
(2015) American Journal of Ophthalmology, 159 (3), pp. 457-462. Cited 2 times.

DOI: 10.1016/j.ajo.2014.11.026


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Campus Box 8096St Louis, MO, United States
b Department of Cell Biology and Physiology, Washington University School of MedicineSt Louis, MO, United States


Abstract
Purpose To measure oxygen (pO2) in eyes of patients undergoing intraocular surgery and identify correlations with central corneal thickness (CCT). Design Prospective, cross-sectional study. Methods setting: Institutional. patient population: 124 patients undergoing cataract and/or glaucoma surgery. observation procedure: Prior to surgery, an oxygen sensor was introduced into the anterior chamber (AC) via peripheral corneal paracentesis. The tip of the flexible fiberoptic probe was positioned for 3 measurements in all patients: (1) near central corneal endothelium; (2) in mid-AC; and (3) in AC angle. In patients undergoing cataract extraction, additional measurements were taken (4) at the anterior lens surface and (5) in the posterior chamber. main outcome measures: pO2 measurements at 5 locations within the eye were compared to central corneal thickness measurements by multivariate regression analyses. Results There was a statistically significant inverse correlation between CCT and pO2 in the anterior chamber angle (P =.048). pO2 was not significantly related to CCT at any other location, including beneath the central cornea. Regression analysis relating CCT to age, race, and oxygen levels in all 5 locations in the anterior segment revealed an association of a thinner cornea with increasing age (P =.007). Conclusions Physiologic correlations with central corneal thickness may provide clues to understanding why a thinner cornea increases the risk of open glaucoma. Associations between glaucoma risk, CCT, and pO2 in the AC angle suggest that exposure of the outflow system to increased oxygen or oxygen metabolites may increase oxidative damage to the trabecular meshwork cells, resulting in elevation of intraocular pressure.


Document Type: Article
Source: Scopus




Tung, T.H.
Clinical strategies to enhance nerve regeneration
(2015) Neural Regeneration Research, 10 (1), pp. 22-24. 

DOI: 10.4103/1673-5374.150641


Center for Nerve Injury and Paralysis, Microsurgical Reconstruction, Division of Plastic and Reconstructive Surgery, Washington University School of MedicineSaint Louis, MO, United States


Document Type: Note
Source: Scopus




Purgert, R.J.a , Peralta, E.b , McClelland, C.M.c , Van Stavern, G.P.c
Combined anterior ischemic optic neuropathy and hemiretinal artery occlusion during hemodialysis
(2015) Canadian Journal of Ophthalmology, 50 (1), pp. e19-e21. 

DOI: 10.1016/j.jcjo.2014.10.019


a School of Medicine, Washington University School of MedicineSt. Louis, United States
b Retina Center of St. Louis, United States
c Department of Ophthalmology and Visual Sciences, Washington University School of Medicine in St. LouisSt. Louis, MO, United States


Document Type: Letter
Source: Scopus




Price, A.R.a b , Bonner, M.F.a , Peelle, J.E.c , Grossman, M.a
Converging evidence for the neuroanatomic basis of combinatorial semantics in the angular gyrus
(2015) Journal of Neuroscience, 35 (7), pp. 3276-3284. 

DOI: 10.1523/JNEUROSCL3446-14.2015


a Penn FTD Center and Department of Neurology, University of PennsylvaniaPhiladelphia, PA, United States
b Neuroscience Graduate Group, University of PennsylvaniaPhiladelphia, PA, United States
c Department of Otolaryngology, Washington UniversitySt. Louis, MI, United States


Abstract
Human thought and language rely on the brain's ability to combine conceptual information. This fundamental process supports the construction of complex concepts from basic constituents. For example, both "jacket" and "plaid" can be represented as individual concepts, but they can also be integrated to form the more complex representation "plaid jacket." Although this process is central to the expression and comprehension of language, little is known about its neural basis. Here we present evidence for a neuroanatomic model of conceptual combination from three experiments. We predicted that the highly integrative region of heteromodal association cortex in the angular gyrus would be critical for conceptual combination, given its anatomic connectivity and its strong association with semantic memory in functional neuroimaging studies. Consistent with this hypothesis, we found that the process of combining concepts to form meaningful representations specifically modulates neural activity in the angular gyrus of healthy adults, independent of the modality of the semantic content integrated. We also found that individual differences in the structure of the angular gyrus in healthy adults are related to variability in behavioral performance on the conceptual combination task. Finally, in a group of patients with neurodegenerative disease, we found that the degree of atrophy in the angular gyrus is specifically related to impaired performance on combinatorial processing. These converging anatomic findings are consistent with a critical role for the angular gyrus in conceptual combination.


Author Keywords
Angular gyrus;  Combinatorial semantics;  Compositionality;  Conceptual combination;  Semantic integration;  Semantic memory


Document Type: Article
Source: Scopus




Lee, H.-J.a , Dietrich, H.H.b c d , Han, B.H.b c , Zipfel, G.J.b c
Development of an ex vivo model for the study of cerebrovascular function utilizing isolated mouse olfactory artery
(2015) Journal of Korean Neurosurgical Society, 57 (1), pp. 1-5. 

DOI: 10.3340/jkns.2015.57.1.1


a Department of Neurological Surgery, The Catholic University of Korea, Daejeon St. Mary’s Hospital, Daejeon, KoreaHope Center for Neurological Disorders, Washington University School of MedicineSt Louis, MO, United States
b Department of Neurological Surgery, Washington University School of MedicineSt Louis, MO, United States
c Alzheimers Disease Research Center, Washington University School of MedicineSt Louis, MO, United States
d Washington University School of MedicineSt Louis, MO, United States


Abstract
Objective : Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. Methods : The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately –500 μm in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). Results : We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin PGH2. Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. Conclusion : Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models.


Author Keywords
Cerebral artery;  Vasoconstriction;  Vasodilation


Document Type: Article
Source: Scopus




Eling, P.a , Finger, S.b , Whitaker, H.c
Franz Joseph gall and music: The faculty and the bump
(2015) Progress in Brain Research, 216, pp. 3-32. 

DOI: 10.1016/bs.pbr.2014.11.001


a Department of Psychology, Radboud University Nijmegen, Donders Institute for Brain, Cognition and BehaviourNijmegen, Netherlands
b Department of Psychology, Washington UniversitySt. Louis, MO, United States
c Department of Psychology, Northern Michigan UniversityMarquette, MI, United States


Abstract
The traditional story maintains that Franz Joseph Gall's (1758-1828) scientific program began with his observations of schoolmates with bulging eyes and good verbal memories. But his search to understand human nature, in particular individual differences in capacities, passions, and tendencies, can also be traced to other important observations, one being of a young girl with an exceptional talent for music. Rejecting contemporary notions of cognition, Gall concluded that behavior results from the interaction of a limited set of basic faculties, each with its own processes for perception and memory, each with its own territory in both cerebral or cerebellar cortices. Gall identified 27 faculties, one being the sense of tone relations or music. The description of the latter is identical in both his Anatomie et Physiologie and Sur les Fonctions du Cerveau et sur Celles de Chacune de ses Parties, where he provided positive and negative evidences and discussed findings from humans and lower animals, for the faculty. The localization of the cortical faculty for talented musicians, he explained, is demonstrated by a "bump" on each side of the skull just above the angle of the eye; hence, the lower forehead of musicians is broader or squarer than in other individuals. Additionally, differences between singing and nonsinging birds also correlate with cranial features. Gall even brought age, racial, and national differences into the picture. What he wrote about music reveals much about his science and creative thinking.


Author Keywords
Amusia;  Cortical localization of function;  Craniology;  Gall (Franz Joseph);  Music faculty;  Musicians;  Organology;  Phrenology;  Physiognomy;  Spurzheim (Johann)


Document Type: Article
Source: Scopus




Ma, Y.a , Smith, C.E.a , Lai, C.-Q.a , Irvin, M.R.b , Parnell, L.D.a , Lee, Y.-C.a , Pham, L.a , Aslibekyan, S.b , Claas, S.A.b , Tsai, M.Y.c , Borecki, I.B.d , Kabagambe, E.K.e , Berciano, S.f , Ordovás, J.M.a f g , Absher, D.M.h , Arnett, D.K.b
Genetic variants modify the effect of age on APOE methylation in the genetics of lipid lowering drugs and diet network study
(2015) Aging Cell, 14 (1), pp. 49-59. 

DOI: 10.1111/acel.12293


a Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts UniversityBoston, MA, United States
b Department of Epidemiology, University of Alabama at BirminghamBirmingham, AL, United States
c Department of Laboratory Medicine and Pathology, University of MinnesotaMinneapolis, MN, United States
d Department of Genetics, Washington University School of MedicineSt. Louis, MO, United States
e Department of Medicine, Vanderbilt UniversityNashville, TN, United States
f Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD)Madrid, Spain
g Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC)Madrid, Spain
h Hudson Alpha Institute for BiotechnologyHuntsville, AL, United States


Abstract
Although apolipoprotein E (APOE) variants are associated with age-related diseases, the underlying mechanism is unknown and DNA methylation may be a potential one. With methylation data, measured by the Infinium Human Methylation 450 array, from 993 participants (age ranging from 18 to 87 years) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, and from Encyclopedia of DNA Elements (ENCODE) consortium, combined with published methylation datasets, we described the methylation pattern of 13 CpG sites within APOE locus, their correlations with gene expression across cell types, and their relationships with age, plasma lipids, and sequence variants. Based on methylation levels and the genetic regions, we categorized the 13 APOE CpG sites into three groups: Group 1 showed hypermethylation (> 50%) and were located in the promoter region, Group 2 exhibited hypomethylation (< 50%) and were located in the first two exons and introns, and Group 3 showed hypermethylation (> 50%) and were located in the exon 4. APOE methylation was negatively correlated with gene expression (minimum r = -0.66, P = 0.004). APOE methylation was significantly associated with age (minimum P = 2.06E-08) and plasma total cholesterol (minimum P = 3.53E-03). Finally, APOE methylation patterns differed across APOE ε variants (minimum P = 3.51E-05) and the promoter variant rs405509 (minimum P = 0.01), which further showed a significant interaction with age (P = 0.03). These findings suggest that methylation may be a potential mechanistic explanation for APOE functions related to aging and call for further molecular mechanistic studies.


Author Keywords
Age;  Apolipoprotein E;  DNA methylation;  Epidemiology;  Interaction;  Variants


Document Type: Article
Source: Scopus




Lin, L.a , Xia, J.a b , Wong, T.T.W.a , Li, L.a , Wang, L.V.a
In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography
(2015) Journal of Biomedical Optics, 20 (1), art. no. 016019, . 

DOI: 10.1117/1.JBO.20.1.016019


a Washington University in St. Louis, Optical Imaging Laboratory, Department of Biomedical EngineeringSt. Louis, MO, United States
b State University of New York, University at Buffalo, Department of Biomedical EngineeringBuffalo, NY, United States


Abstract
Using internal illumination with an optical fiber in the oral cavity, we demonstrate, for the first time, photoacoustic computed tomography (PACT) of the deep brain of rats in vivo. The experiment was performed on a full-ring-array PACT system, with the capability of providing high-speed cross-sectional imaging of the brain. Compared with external illumination through the cranial skull, internal illumination delivers more light to the base of the brain. Consequently, in vivo photoacoustic images clearly reveal deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.


Author Keywords
anatomic imaging;  deep brain imaging;  internal illumination;  optical fiber;  oral-cavity illumination;  photoacoustic computed tomography


Document Type: Article
Source: Scopus




Søvik, E.a , Perry, C.J.b , Barron, A.B.c
Insect Reward Systems: Comparing Flies and Bees
(2015) Advances in Insect Physiology, . Article in Press. 

DOI: 10.1016/bs.aiip.2014.12.006


a Department of Biology, Washington University in St. Louis, St. Louis, Missouri, USA
b School of Chemical and Biological Sciences, Queen Mary University, London, United Kingdom
c Department of Biological Sciences, Macquarie University, Sydney, New South Wales, Australia


Abstract
Many elements of animal behaviour are organised by an innate reward-seeking drive stemming from neurobiological reward systems. The behavioural concept of reward and its neurobiological substrates was initially developed in mammalian systems, and there it has become clear that several novel social behaviours evolved through the co-option of reward pathways. Only more recently has reward been explored in insects. In this review, we consider current knowledge about reward pathways in the two predominant insect models: Drosophila melanogaster and the honey bee Apis mellifera. These two models are phylogenetically distantly related and have vastly different ecologies: fruit flies are mostly solitary while honey bees live in complex societies involving social foraging and brood care. Initially, it was assumed the reward system was essentially similar between these two organisms, but more recent studies have appeared to highlight quite significant differences. Here, we critically evaluate apparent differences in the neurobiology of the reward system between these organisms. We discuss which differences may be real and which may be reflective of the very different modes of analysis applied in these two models. Finally, we discuss how modification of reward systems might have contributed to social evolution in insects.


Author Keywords
Drosophila;  Dopamine;  Honey bee;  Invertebrate neurobiology;  OA-VUMa2;  Octopamine;  Reward seeking;  Social evolution;  Social reward;  VUMmx1


Document Type: Article in Press
Source: Scopus




Vedhara, K.a , Gill, S.a , Eldesouky, L.b , Campbell, B.K.c , Arevalo, J.M.G.d , Ma, J.d , Cole, S.W.d
Personality and gene expression: Do individual differences exist in the leukocyte transcriptome?
(2015) Psychoneuroendocrinology, 52 (1), pp. 72-82. 

DOI: 10.1016/j.psyneuen.2014.10.028


a School of Medicine, Division of Primary Care, University of Nottingham, Tower Building, University ParkNottingham, United Kingdom
b Department of Psychology, Washington UniversitySt. Louis, MO, United States
c School of Medicine, Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, D floor, East Block QMCNottingham, United Kingdom
d Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine, University of CaliforniaLos Angeles, CA, United States


Abstract
Background: The temporal and situational stability of personality has led generations of researchers to hypothesize that personality may have enduring effects on health, but the biological mechanisms of such relationships remain poorly understood. In the present study, we utilized a functional genomics approach to examine the relationship between the 5 major dimensions of personality and patterns of gene expression as predicted by 'behavioural immune response' theory. We specifically focussed on two sets of genes previously linked to stress, threat, and adverse socio-environmental conditions: pro-inflammatory genes and genes involved in Type I interferon and antibody responses. Methods: An opportunity sample of 121 healthy individuals was recruited (86 females; mean age 24 years). Individuals completed a validated measure of personality; questions relating to current health behaviours; and provided a 5. ml sample of peripheral blood for gene expression analysis. Results: Extraversion was associated with increased expression of pro-inflammatory genes and Conscientiousness was associated with reduced expression of pro-inflammatory genes. Both associations were independent of health behaviours, negative affect, and leukocyte subset distributions. Antiviral and antibody-related gene expression was not associated with any personality dimension. Conclusions: The present data shed new light on the long-observed epidemiological associations between personality, physical health, and human longevity. Further research is required to elucidate the biological mechanisms underlying these associations.


Author Keywords
Antibody;  Antiviral;  Gene expression;  Immunity;  Personality;  Pro-inflammatory


Document Type: Article
Source: Scopus




Finnerup, N.B.a , Attal, N.b c , Haroutounian, S.d , McNicol, E.e , Baron, R.f , Dworkin, R.H.g , Gilron, I.h , Haanpää, M.i j , Hansson, P.k l , Jensen, T.S.a m , Kamerman, P.R.n , Lund, K.a , Moore, A.o , Raja, S.N.p , Rice, A.S.C.q r , Rowbotham, M.s , Sena, E.t u , Siddall, P.v w , Smith, B.H.x , Wallace, M.y
Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis
(2015) The Lancet Neurology, 14 (2), pp. 162-173. 

DOI: 10.1016/S1474-4422(14)70251-0


a Danish Pain Research Center, Department of Clinical Medicine, Aarhus UniversityAarhus, Denmark
b INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, Assistance Publique Hôpitaux de ParisBoulogne-Billancourt, France
c Université Versailles Saint-Quentin, France
d Division of Clinical and Translational Research, Department of Anesthesiology, Washington University School of MedicineSt Louis, MO, United States
e Departments of Anesthesiology and Pharmacy, Tufts Medical CenterBoston, MA, United States
f Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus KielKiel, Germany
g Department of Anesthesiology and Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and DentistryRochester, NY, United States
h Department of Anesthesiology and Perioperative Medicine and Biomedical and Molecular Sciences, Queen's UniversityKingston, ON, Canada
i Department of Neurosurgery, Helsinki University Central HospitalHelsinki, Finland
j Mutual Insurance Company EteraHelsinki, Finland
k Department of Pain Management and Research, Oslo University HospitalOslo, Norway
l Department of Molecular Medicine and Surgery, Karolinska InstitutetStockholm, Sweden
m Department of Neurology, Aarhus University HospitalAarhus, Denmark
n Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, South Africa
o Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, Pain Research, Churchill HospitalOxford, United Kingdom
p Johns Hopkins School of Medicine, Division of Pain Medicine, Department of Anesthesiology and Critical Care MedicineBaltimore, MD, United States
q Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, United Kingdom
r Pain Medicine, Chelsea and Westminster Hospital NHS Foundation TrustLondon, United Kingdom
s California Pacific Medical Center Research Institute, UCSF Pain Management CenterSan Francisco, CA, United States
t Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of EdinburghEdinburgh, United Kingdom
u Florey Institute of Neuroscience and Mental HealthMelbourne, VIC, Australia
v Department of Pain Management, Greenwich HospitalHammondCare, Sydney, NSW, Australia
w Kolling Institute, Sydney Medical School-Northern, University of SydneySydney, NSW, Australia
x Division of Population Health Sciences, University of Dundee, Ninewells Hospital and Medical SchoolDundee, Scotland, United Kingdom
y Division of Pain Medicine, Department of Anesthesiology, UCSDSan Diego, CA, United States


Abstract
Background: New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods: Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fixed-effects Mantel-Haenszel method. Findings: 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-reviewed journals reported greater effects than did unpublished studies (r2 9·3%, p=0·009). Trial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2-8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5-9·4) for pregabalin; 7·2 (5·9-9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4-19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, final quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These findings permitted a strong recommendation for use and proposal as first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation: Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest efficacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profiling probably account for moderate trial outcomes and should be taken into account in future studies. Funding: NeuPSIG of the International Association for the Study of Pain.


Document Type: Article
Source: Scopus




Garfield, L.D.a c , Brown, D.S.a , Allaire, B.T.b , Ross, R.E.a , Nicol, G.E.a , Raghavan, R.a
Psychotropic drug use among preschool children in the medicaid program from 36 states
(2015) American Journal of Public Health, 105 (3), pp. 524-529. 

DOI: 10.2105/AJPH.2014.302258


a Washington UniversitySt Louis, MO, United States
b RTI International, Research Triangle ParkNC, United States
c Mercy ResearchSt Louis, MO, United States


Abstract
Objectives. We determined the prevalence of and indications for psychotropic medication among preschool children in Medicaid.

Methods. We obtained 2000 to 2003 Medicaid Analytic Extract data from 36 states. We followed children in 2 cohorts, born in 1999 and 2000, up to age 4 years. We used logistic regression to model odds of receiving medications for (1) attention-deficit disorder/attention-deficit hyperactivity disorder, (2) depression or anxiety, and (3) psychotic illness or bipolar.

Results. Overall, 1.19% of children received at least 1 psychotropic drug. Medications for attention-deficit disorder/attention-deficit hyperactivity disorder treatment were most common (0.61% of all children), followed by depression or anxiety (0.59%) and psychotic illness or bipolar (0.24%). Among children, boys, those of other or unknown race compared with White, and those with other insurance compared with fee for service-only had higher odds of receiving a prescription (odds ratio [OR] = 1.80 [95% confidence interval (CI) = 1.74, 1.86], 1.87 [1.66, 1.85], and 1.14 [1.01, 1.28], respectively), whereas Black and Hispanic children had lower odds (OR = 0.51 [95% CI = 0.48, 0.53] and 0.37 [0.34, 0.39], respectively).

Conclusions. Preschoolers are receiving psychotropic medications despite limited evidence supporting safety or efficacy. Future research should focus on implementing medication use practice parameters in infant and toddler clinics, and expanding psychosocial interventions for young children with behavioral problems.


Document Type: Article
Source: Scopus




Wang, L.-S.a eb eb , Naj, A.C.b eb eb , Graham, R.R.c , Crane, P.K.d , Kunkle, B.W.e , Cruchaga, C.f g , Gonzalez Murcia, J.D.h , Cannon-Albright, L.i j , Baldwin, C.T.k , Zetterberg, H.l m , Blennow, K.m , Kukull, W.A.n , Faber, K.M.o , Schupf, N.p q r , Norton, M.C.s t , Tschanz, J.T.t , Munger, R.G.u , Corcoran, C.D.v , Rogaeva, E.w , Albert, M.S.aj , Albin, R.L.ak al am , Apostolova, L.G.an , Arnold, S.E.ao , Barber, R.ap , Barmada, M.M.aq , Barnes, L.L.ar as , Beach, T.G.at , Becker, J.T.au aw , Beecham, G.W.e ah av , Beekly, D.ax , Bennett, D.A.ar ay , Bigio, E.H.az ba , Bird, T.D.bb bc , Blacker, D.bd be , Boeve, B.F.bf , Bowen, J.D.bg , Boxer, A.an , Burke, J.R.bh , Buxbaum, J.D.bi bj bk , Cairns, N.J.bl , Cao, C.bm , Carlson, C.S.bn , Carroll, S.L.bo , Chui, H.C.bp , Clark, D.G.bq , Cribbs, D.H.an , Crocco, E.A.aa , DeCarli, C.br , DeKosky, S.T.bs bt , Demirci, F.Y.aq , Dick, M.eb , Dickson, D.W.bu bv , Duara, R.bw , Ertekin-Taner, N.bv bx , Fallon, K.B.bo , Farlow, M.R.by , Ferris, S.bz , Frosch, M.P.ca , Galasko, D.R.cb , Ganguli, M.au , Gearing, M.cc cd , Geschwind, D.H.ce , Ghetti, B.cf , Gilbert, J.R.e ah , Glass, J.D.cg , Graff-Radford, N.R.bv bx , Growdon, J.H.ch , Hamilton, R.L.eb , Hamilton-Nelson, K.L.e ci , Harrell, L.E.bq , Head, E.cj , Honig, L.S.q ai , Hulette, C.M.ck , Hyman, B.T.ch , Jarvik, G.P.cl cm , Jicha, G.A.cn , Jin, L.-W.co , Jun, G.ad ae cp , Kamboh, M.I.aq cq , Karydas, A.an , Kaye, J.A.cr cs , Kim, R.ct , Koo, E.H.cb , Kowall, N.W.af cu , Kramer, J.H.eb , Kramer, P.cr cv cw , LaFerla, F.M.cx , Lah, J.J.cg , Leverenz, J.B.cy , Levey, A.I.cg , Li, G.cz , Lieberman, A.P.da , Lopez, O.L.cq , Lunetta, K.L.ad , Lyketsos, C.G.db , Mack, W.J.dc , Marson, D.C.bq , Martin, E.R.e , Martiniuk, F.ah dd , Mash, D.C.de , Masliah, E.cb df , McCormick, W.C.d , McCurry, S.M.dg , McDavid, A.N.bn , McKee, A.C.af cu , Mesulam, M.M.ba dh , Miller, B.L.eb , Miller, C.A.eb , Miller, J.W.an co di , Montine, T.J.cy , Morris, J.C.bl dj , Murrell, J.R.o cf , Olichney, J.M.br , Parisi, J.E.dk dl , Perry, W.e , Peskind, E.cz , Petersen, R.C.bf , Pierce, A.an , Poon, W.W.bu , Potter, H.bm , Quinn, J.F.cr , Raj, A.bm , Raskind, M.cz , Reiman, E.M.dm dn do , Reisberg, B.bz dp , Reitz, C.q r ai , Ringman, J.M.eb , Roberson, E.D.an bq , Rosen, H.J.eb , Rosenberg, R.N.an dq , Sano, M.bj , Saykin, A.J.o dr , Schneider, J.A.ar ds , Schneider, L.S.bp dt , Seeley, W.W.an , Smith, A.G.bm , Sonnen, J.A.cy , Spina, S.cf , Stern, R.A.af , Tanzi, R.E.ch , Thornton-Wells, T.A.ac , Trojanowski, J.Q.a , Troncoso, J.C.du , Tsuang, D.W.bb cz , Van Deerlin, V.M.a , Van Eldik, L.J.dv , Vardarajan, B.N.q r ai , Vinters, H.V.an ct , Vonsattel, J.P.q dw , Weintraub, S.ba dx , Welsh-Bohmer, K.A.bh dy , Williamson, J.q , Wishnek, S.e , Woltjer, R.L.dz , Wright, C.B.ea , Younkin, S.G.bv , Yu, C.-E.d , Yu, L.ar , Lin, C.-F.a , Dombroski, B.A.a , Cantwell, L.B.a , Partch, A.a , Valladares, O.a , Hakonarson, H.x , St George-Hyslop, P.w y , Green, R.C.z , Goate, A.M.f g , Foroud, T.M.o , Carney, R.M.aa , Larson, E.B.d ab , Behrens, T.W.c , Kauwe, J.S.K.h , Haines, J.L.ac , Farrer, L.A.h ad ae af ag , Pericak-Vance, M.A.e ah , Mayeux, R.q r ai , Schellenberg, G.D.a
Rarity of the alzheimer disease-protective APP A673T variant in the United States
(2015) JAMA Neurology, 72 (2), pp. 209-216. 

DOI: 10.1001/jamaneurol.2014.2157


a Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Stellar Chance Laboratories, 422 Curie BlvdPhiladelphia, PA, United States
b Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of MedicinePhiladelphia, United States
c Department of Human Genetics, Genentech IncSouth San Francisco, CA, United States
d Department of Medicine, University of WashingtonSeattle, United States
e John P. Hussman Institute for Human Genomics, University of MiamiMiami, FL, United States
f Department of Psychiatry, Washington University School of MedicineSt Louis, MO, United States
g Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of MedicineSt Louis, MO, United States
h Department of Biology, Brigham Young UniversityProvo, UT, United States
i Division of Genetic Epidemiology, Department of Medicine, University of Utah School of MedicineSalt Lake City, United States
j George E. Wahlen Department of Veterans Affairs Medical CenterSalt Lake City, UT, United States
k Biomedical Genetics, Department of Medicine, Boston UniversityBoston, MA, United States
l Institute of Neurology, University College LondonLondon, United Kingdom
m Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, University of Gothenburg Sahlgrenska University HospitalMölndal, Sweden
n Department of Epidemiology, University of WashingtonSeattle, United States
o Department of Medical and Molecular Genetics, Indiana UniversityIndianapolis, United States
p Department of Epidemiology, Mailman School of Public Health, Columbia UniversityNew York, NY, United States
q Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia UniversityNew York, NY, United States
r Gertrude H. Sergievsky Center, Columbia UniversityNew York, NY, United States
s Department of Family, Consumer, and Human Development, Utah State UniversityLogan, United States
t Department of Psychology, Utah State UniversityLogan, United States
u Department of Nutrition, Dietetics, and Food Sciences, Utah State UniversityLogan, United States
v Department of Mathematics and Statistics, Utah State UniversityLogan, United States
w Tanz Centre for Research in Neurodegenerative Disease, University of TorontoToronto, ON, Canada
x Center for Applied Genomics, Children's Hospital of PhiladelphiaPhiladelphia, PA, United States
y Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of CambridgeCambridge, United Kingdom
z Division of Genetics, Department of Medicine, Brigham and Women's Hospital/Harvard Medical SchoolBoston, MA, United States
aa Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of MiamiMiami, FL, United States
ab Group Health Research InstituteSeattle, WA, United States
ac Center for Human Genetics and Research, Department of Molecular Physiology and Biophysics, Vanderbilt UniversityNashville, TN, United States
ad Department of Biostatistics, Boston UniversityBoston, MA, United States
ae Department of Ophthalmology, Boston UniversityBoston, MA, United States
af Department of Neurology, Boston UniversityBoston, MA, United States
ag Department of Epidemiology, Boston UniversityBoston, MA, United States
ah Dr John T. Macdonald Foundation Department of Human Genetics, University of MiamiMiami, FL, United States
ai Department of Neurology, Columbia UniversityNew York, New York, United States
aj Department of Neurology, Johns Hopkins UniversityBaltimore, MD, United States
ak Department of Neurology, University of MichiganAnn Arbor, United States
al Geriatric Research, Education, and Clinical Center, VA Ann Arbor Healthcare SystemAnn Arbor, MI, United States
am Michigan Alzheimer's Disease CenterAnn Arbor, United States
an Department of Neurology, University of CaliforniaLos Angeles, United States
ao Department of Psychiatry, University of Pennsylvania Perelman School of MedicinePhiladelphia, United States
ap Department of Pharmacology and Neuroscience, University of North Texas Health Science CenterFort Worth, United States
aq Department of Human Genetics, University of PittsburghPittsburgh, PA, United States
ar Department of Neurological Sciences, Rush University Medical CenterChicago, IL, United States
as Department of Behavioral Sciences, Rush University Medical CenterChicago, IL, United States
at Civin Laboratory for Neuropathology, Banner Sun Health Research InstitutePhoenix, AZ, United States
au Department of Psychiatry, University of Pittsburgh School of MedicinePittsburgh, PA, United States
av Department of Neurology, University of Pittsburgh School of MedicinePittsburgh, PA, United States
aw Department of Psychology, University of Pittsburgh School of MedicinePittsburgh, PA, United States
ax National Alzheimer's Coordinating Center, University of WashingtonSeattle, United States
ay Rush Alzheimer's Disease Center, Rush University Medical CenterChicago, IL, United States
az Department of Pathology, Northwestern University Feinberg School of MedicineChicago, IL, United States
ba Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of MedicineChicago, IL, United States
bb Geriatric Research, Education, and Clinical Center, VA Puget Sound Healthcare SystemSeattle, WA, United States
bc Department of Neurology, University of WashingtonSeattle, United States
bd Department of Epidemiology, Harvard School of Public HealthBoston, MA, United States
be Department of Psychiatry, Massachusetts General Hospital, Harvard Medical SchoolBoston, United States
bf Department of Neurology, Mayo ClinicRochester, MN, United States
bg Swedish Medical CenterSeattle, WA, United States
bh Department of Medicine, Duke UniversityDurham, NC, United States
bi Department of Neuroscience, Mount Sinai School of MedicineNew York, NY, United States
bj Department of Psychiatry, Mount Sinai School of MedicineNew York, NY, United States
bk Department of Genetics and Genomic Sciences, Mount Sinai School of MedicineNew York, NY, United States
bl Department of Pathology and Immunology, Washington University, St LouisMO, United States
bm USF Health Byrd Alzheimer's Institute, University of South FloridaTampa, United States
bn Fred Hutchinson Cancer Research CenterSeattle, WA, United States
bo Department of Pathology, University of Alabama at BirminghamBirmingham, United States
bp Department of Neurology, University of Southern CaliforniaLos Angeles, United States
bq Department of Neurology, University of Alabama at BirminghamBirmingham, United States
br Department of Neurology, University of CaliforniaDavis, Sacramento, United States
bs University of Virginia School of MedicineCharlottesville, United States
bt University of PittsburghPittsburgh, PA, United States
bu Institute for Memory Impairments and Neurological Disorders, University of CaliforniaIrvine, United Kingdom
bv Department of Neuroscience, Mayo ClinicJacksonville, FL, United States
bw Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical CenterMiami Beach, FL, United States
bx Department of Neurology, Mayo ClinicJacksonville, FL, United States
by Department of Neurology, Indiana UniversityIndianapolis, United States
bz Department of Psychiatry, New York UniversityNew York, United States
ca C. S. Kubik Laboratory for Neuropathology, Massachusetts General HospitalCharlestown, United States
cb Department of Neurosciences, University of California, San DiegoSan Diego, United States
cc Department of Pathology and Laboratory Medicine, Emory UniversityAtlanta, GA, United States
cd Alzheimer's Disease Research Center, Emory UniversityAtlanta, GA, United States
ce Neurogenetics Program, University of CaliforniaLos Angeles, United States
cf Department of Pathology and Laboratory Medicine, Indiana UniversityIndianapolis, United States
cg Department of Neurology, Emory UniversityAtlanta, GA, United States
ch Department of Neurology, Massachusetts General Hospital, Harvard Medical SchoolBoston, United States
ci Division of Neuropathology, Department of Pathology, University of PittsburghPittsburgh, PA, United States
cj Department of Molecular and Biomedical Pharmacology, Sanders-Brown Center on Aging, University of KentuckyLexington, United States
ck Department of Pathology, Duke UniversityDurham, NC, United States
cl Department of Genome Sciences, University of WashingtonSeattle, United States
cm Division of Medical Genetics, Department of Medicine, University of WashingtonSeattle, United States
cn Department of Neurology, Sanders-Brown Center on Aging, University of KentuckyLexington, United States
co Department of Pathology and Laboratory Medicine, University of CaliforniaDavis, Sacramento, United States
cp Genetics Program, Department of Medicine, Boston UniversityBoston, MA, United States
cq Alzheimer Disease Research Center, University of PittsburghPittsburgh, PA, United States
cr Department of Neurology, Oregon Health and Science UniversityPortland, United States
cs Department of Neurology, Portland Veterans Affairs Medical CenterPortland, OR, United States
ct Department of Pathology and Laboratory Medicine, University of CaliforniaIrvine, United States
cu Department of Pathology, Boston UniversityBoston, MA, United States
cv Department of Neuropsychology, University of CaliforniaSan Francisco, United States
cw Department of Molecular and Medical Genetics, Oregon Health and Science UniversityPortland, United States
cx Department of Neurobiology and Behavior, University of CaliforniaIrvine, United Kingdom
cy Department of Pathology, University of WashingtonSeattle, United States
cz Department of Psychiatry and Behavioral Sciences, University of Washington School of MedicineSeattle, United States
da Department of Pathology, University of MichiganAnn Arbor, United States
db Department of Psychiatry, Johns Hopkins UniversityBaltimore, MD, United States
dc Department of Preventive Medicine, University of Southern CaliforniaLos Angeles, United States
dd Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York UniversityNew York, United States
de Department of Neurology, University of MiamiMiami, FL, United States
df Department of Pathology, University of California, San DiegoSan Diego, United States
dg Northwest Research Group on Aging, School of Nursing, University of WashingtonSeattle, United States
dh Department of Neurology, Northwestern University Feinberg School of MedicineChicago, IL, United States
di Department of Pathology, University of Southern CaliforniaLos Angeles, United States
dj Department of Neurology, Washington UniversitySt Louis, MO, United States
dk Department of Anatomic Pathology, Mayo Clinic, RochesterMN, United States
dl Department of Laboratory Medicine and Pathology, Mayo ClinicRochester, MN, United States
dm Neurogenomics Division, Translational Genomics Research InstitutePhoenix, AZ, United States
dn Arizona Alzheimer's ConsortiumPhoenix, United States
do Banner Alzheimer's InstitutePhoenix, AZ, United States
dp Alzheimer's Disease Center, New York UniversityNew York, United States
dq Department of Neurology, University of Texas Southwestern Medical CenterDallas, United States
dr Department of Radiology and Imaging Sciences, Indiana UniversityIndianapolis, United States
ds Department of Pathology (Neuropathology), Rush University Medical CenterChicago, IL, United States
dt Department of Psychiatry, University of Southern CaliforniaLos Angeles, United States
du Department of Pathology, Johns Hopkins UniversityBaltimore, MD, United States
dv Department of Anatomy and Neurobiology, Sanders-Brown Center on Aging, University of KentuckyLexington, United States
dw Department of Pathology, Columbia UniversityNew York, NY, United States
dx Department of Psychiatry, Northwestern University Feinberg School of MedicineChicago, IL, United States
dy Department of Psychiatry and Behavioral Sciences, Duke UniversityDurham, NC, United States
dz Department of Pathology, Oregon Health and Science UniversityPortland, United States
ea Department of Neurology, Miller School of Medicine, University of MiamiMiami, FL, United States


Abstract
IMPORTANCE Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.OBJECTIVE To determine the frequency of the APP A673T variant in a large group of elderly cognitively normal controls and AD cases from the United States and in 2 case-control cohorts from Sweden.DESIGN, SETTING, AND PARTICIPANTS Case-control association analysis of variant APP A673T in US and Swedish white individuals comparing AD cases with cognitively intact elderly controls. Participants were ascertained at multiple university-associated medical centers and clinics across the United States and Sweden by study-specific samplingmethods. They were from case-control studies, community-based prospective cohort studies, and studies that ascertained multiplex families from multiple sources.MAIN OUTCOMES AND MEASURES Genotypes for the APP A673T variantwere determined using the Infinium HumanExome V1 Beadchip (Illumina, Inc) and by TaqMan genotyping (Life Technologies).RESULTS The A673T variant genotypes were evaluated in 8943 US AD cases, 10 480 US cognitively normal controls, 862 Swedish AD cases, and 707 Swedish cognitively normal controls.We identified 3 US individuals heterozygous for A673T, including 1 AD case (age at onset, 89 years) and 2 controls (age at last examination, 82 and 77 years). The remaining US samples were homozygous for the alanine (A673) allele. In the Swedish samples, 3 controls were heterozygous for A673T and all AD cases were homozygous for the A673 allele. We also genotyped a US family previously reported to harbor the A673T variant and found a mother-daughter pair, both cognitively normal at ages 72 and 84 years, respectively, who were both heterozygous for A673T; however, all individuals with AD in the family were homozygous for A673.CONCLUSIONS AND RELEVANCE The A673T variant is extremely rare in US cohorts and does not play a substantial role in risk for AD in this population. This variant may be primarily restricted to Icelandic and Scandinavian populations.


Document Type: Article
Source: Scopus




Pepose, J.S.a b , Hayashida, J.b , Hovanesian, J.d , Davies, J.e , Labor, P.K.h , Whitman, J.i , Carter, H.j , Colvard, M.f , Buckhurst, P.J.l , Khodai, O.c , Mittleman, D.k , Feinerman, G.g
Safety and effectiveness of a new toric presbyopia-correcting posterior chamber silicone intraocular lens
(2015) Journal of Cataract and Refractive Surgery, 41 (2), pp. 295-305. 

DOI: 10.1016/j.jcrs.2014.05.043


a Pepose Vision Institute, 1815 Clarkson RoadChesterfield, MO, United States
b Department of Ophthalmology and Visual Sciences, Washington University School of MedicineSt. Louis, MO, United States
c Bausch and LombAliso Viejo, United States
d Harvard Eye AssociatesLaguna Hills, United States
e Davies Eye CenterCarlsbad, United States
f Colvard-Kandavel Eye CenterEncino, United States
g Feinerman Vision CenterNewport Beach, CA, United States
h Eye Consultants of TexasGrapevine, United States
i Key-Whitman Eye Center, United States
j Carter Eye CenterDallas, TX, United States
k Mittleman Eye CenterWest Palm Beach, FL, United States
l Plymouth UniversityPlymouth, United Kingdom


Abstract
Purpose To evaluate the safety and effectiveness of the Trulign toric intraocular lens (IOL) in adults with cataract. Setting Eight private practices in the United States and 1 in Canada. Design Prospective randomized single-masked multicenter study. Methods A toric IOL (1.25 D, 2.00 D, or 2.75 D, determined by a toric calculator) was implanted in eligible patients with age-related cataract requiring a 16.00 to 27.00 diopter (D) spherical IOL power and with a predicted postoperative astigmatism of 0.83 to 2.50 D. Eyes within the lowest cylinder range (predicted postoperative astigmatism 0.83 to 1.32 D) were randomized in a 1:1 ratio between the 1.25 D toric IOL group and the nontoric accommodating IOL (Crystalens) control group. Results The toric 1.25 D group had a statistically significantly greater percentage reduction in absolute cylinder (P <.001) and uncorrected distance visual acuity (P =.002) than the control group at the 120- to 180-day visit. The mean monocular uncorrected vision at distance, intermediate, and near was 20/25, 20/22, and 20/39, respectively, with the 1.25 D, 2.00 D, and 2.75 D toric IOLs in aggregate (toric group). In addition, 96.1% of patients (123/128) had 5.0 degrees or less absolute IOL rotation postoperatively. Regarding safety, the endpoints for preservation of corrected visual acuity and the incidence of complications and adverse events were met. Conclusion The toric IOL was safe and effective in reducing the effects of preoperative corneal astigmatism and provided excellent uncorrected distance and intermediate vision and functional near vision. Financial Disclosures Dr. Pepose is a consultant to Bausch & Lomb and was medical monitor of this study. Drs. Buckhurst, Whitman, Feinerman, Hovanesian, Davies, Labor, and Carter are consultants to Bausch & Lomb. At the time of the study, Drs. Hayashida, and Khodai were employees of Bausch & Lomb. Drs. Colvard and Mittleman have financial or proprietary interest in any material or method mentioned.


Document Type: Article
Source: Scopus




Mickle, A.D.a c , Shepherd, A.J.a c , Mohapatra, D.P.a b c
Sensory TRP Channels: The Key Transducers of Nociception and Pain
(2015) Progress in Molecular Biology and Translational Science, . Article in Press. 

DOI: 10.1016/bs.pmbts.2015.01.002


a Department of Pharmacology, The University of Iowa Roy J. and Lucile A. Carver College of Medicine, Iowa City, Iowa, USA
b Department of Anesthesia, The University of Iowa Roy J. and Lucile A. Carver College of Medicine, Iowa City, Iowa, USA
c Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA


Abstract
Peripheral detection of nociceptive and painful stimuli by sensory neurons involves a complex repertoire of molecular detectors and/or transducers on distinct subsets of nerve fibers. The majority of such molecular detectors/transducers belong to the transient receptor potential (TRP) family of cation channels, which comprise both specific receptors for distinct nociceptive stimuli, as well as for multiple stimuli. This chapter discusses the classification, distribution, and functional properties of individual TRP channel types that have been implicated in various nociceptive and/or painful conditions.


Author Keywords
Nociception;  Pain;  TRP channel;  TRPA1;  TRPM3;  TRPM8;  TRPV1;  TRPV2;  TRPV3;  TRPV4


Document Type: Article in Press
Source: Scopus




Finger, S.a , Sironi, V.A.b , Riva, M.A.b
Somnambulism in Verdi's Macbeth and Bellini's La Sonnambula: Opera, sleepwalking, and medicine
(2015) Progress in Brain Research, 216, pp. 357-358. 

DOI: 10.1016/bs.pbr.2014.11.015


a Department of Psychology, Washington UniversitySt. Louis, MO, United States
b Research Centre on History of Biomedical Thought, Centro Studi sulla Storia del Pensiero Biomedico (CESPEB), University of Milano BicoccaMonza, Italy


Abstract
The arts can provide unique ways for determining how people not directly involved in medicine were viewing and informing others about physical and mental disorders. With operas, one need only think about how various perturbations of madness have been portrayed. Somnambulism has long been a particularly perplexing disorder, both to physicians and the laity, and it features in a number of operas. Two mid-nineteenth-century masterpieces are examined in detail in this contribution: Verdi's Macbeth and Bellini's La Sonnambula. In the former, the sleepwalking scene is faithful to what Shakespeare's had written early in the seventeenth century, a time of witchcraft, superstition, and the belief that nocturnal wanderings might be caused by guilt. In Bellini's opera, in contrast, the victim is an innocent girl who suffers from a quirk of nature, hence eliciting sympathy and compassion. By examining the early literature on somnambulism and comparing this disorder in these operas, we can see how thinking about this condition has changed and, more generally, how music was helping to generate new ways of thinking about specific diseases and medicine.


Author Keywords
Bellini (Vincenzo);  History of medicine;  History of neuroscience;  History of sleep;  Italian opera;  La sonnambula;  Lady macbeth;  Macbeth;  Shakespeare;  Sleep disorders;  Sleepwalking;  Somnambulism;  Verdi (Giuseppe)


Document Type: Article
Source: Scopus




Jirawison, C.a , Yen, M.b c , Leenasirimakul, P.a , Chen, J.b d e , Guadanant, S.a , Kunavisarut, P.f , Patikulsila, D.f , Watanachai, N.f , Ausayakhun, S.f , Heiden, D.g , Holland, G.N.d , Margolis, T.P.b h i , Keenan, J.D.b h
Telemedicine screening for cytomegalovirus retinitis at the point of care for human immunodeficiency virus infection
(2015) JAMA Ophthalmology, 133 (2), pp. 198-205. 

DOI: 10.1001/jamaophthalmol.2014.4766


a Department of Ophthalmology, Nakornping HospitalChiang Mai, Thailand
b Francis I. Proctor Foundation for Research in Ophthalmology, University of CaliforniaSan Francisco, United States
c Icahn School of Medicine at Mount SinaiNew York, NY, United States
d Ocular Inflammatory Disease Center, Jules Stein Eye Institute, University of CaliforniaLos Angeles, United States
e Department of Ophthalmology, David Geffen School of Medicine, University of CaliforniaLos Angeles, United States
f Department of Ophthalmology, Faculty of Medicine, Chiang Mai UniversityChiang Mai, Thailand
g Department of Ophthalmology, California Pacific Medical CenterSan Francisco, United States
h Department of Ophthalmology, University of CaliforniaSan Francisco, United States
i Department of Ophthalmology and Visual Sciences, Washington University School of MedicineSt Louis, MO, United States


Abstract
IMPORTANCE Cytomegalovirus (CMV) retinitis is a leading cause of blindness in many developing countries, likely the result of inadequate screening. Telemedicine screening for CMV retinitis instituted at the point of care for human immunodeficiency virus (HIV) infection may allow for earlier detection. OBJECTIVES To determine the diagnostic accuracy of retinal photography in detecting CMV retinitis at the point of HIV care and to characterize the clinical manifestations of CMV retinitis detected through the screening program. DESIGN, SETTING, AND PARTICIPANTS We enrolled 103 participants from a population of 258 patients with HIV and a CD4 level of less than 100/ìL treated at an HIV clinic in Thailand from June 2010 through June 2012.We captured mosaic fundus photographs through a dilated pupil using a digital fundus camera. An experienced on-site ophthalmologist masked to the results of the fundus images subsequently examined each eye with indirect ophthalmoscopy and recorded the clinical findings on a standardized form. Three remote graders evaluated each image for CMV retinitis. INTERVENTION Fundus photography and indirect ophthalmoscopy. MAIN OUTCOMES AND MEASURES Sensitivity and specificity of telemedicine relative to indirect ophthalmoscopy for diagnosis of CMV retinitis and clinical features of CMV retinitis lesions. RESULTS Sixteen patients (15.5%) were diagnosed as having CMV retinitis, of whom 5 (31%) had bilateral disease. Of the 21 eyes (10.2%) with CMV retinitis, 7 (33%) had visual symptoms. Retinitis lesions occupied less than 10% of the total retinal surface area in 13 of 21 eyes (62%) and did not involve the posterior pole (ie, zone 1) in 15 of 21 eyes (71%). Mean logMAR visual acuity in affected eyes was 0.41 (95%CI, 0.11-0.71; Snellen equivalent, 20/50 [95%CI, 20/25-20/100]). The mean sensitivity for the 3 remote graders in detecting CMV retinitis on fundus photography was 30.2%(95%CI, 10.5%-52.4%), and mean specificity was 99.1% (95%CI, 97.8%-100.0%). The CMV retinitis lesions missed by the remote graders (false-negative findings) were more likely to be small (P =.001) and located in the peripheral retina (P =.04). CONCLUSIONS AND RELEVANCE Patients undergoing screening at a clinic for HIV treatment had less extensive retinitis than patients in recent reports from an ophthalmology clinic. Retinal photography with the camera used in this study was not highly sensitive in detecting CMV retinitis but may identify disease with an immediate threat to vision. Improved accuracy will require a camera that can more easily image the peripheral retina.


Document Type: Article
Source: Scopus




Hughes, M.L.a , Lowe, D.A.a , Shine, H.E.a , Carpenter, B.D.b , Balsis, S.a
Using the alzheimer's association web site to improve knowledge of alzheimer's disease in health care providers
(2015) American Journal of Alzheimer's Disease and other Dementias, 30 (1), pp. 98-100. 

DOI: 10.1177/1533317514559827


a Department of Psychology, Texas A and M UniversityCollege Station, TX, United States
b Department of Psychology, Washington University in St LouisSt Louis, MO, United States


Abstract
Background: The purpose of the current study was to investigate whether an informative Web site is effective at producing higher scores for an individuals knowledge of Alzheimers disease (AD) relative to those who do not visit a Web site. Methods: A total of 552 participants completed the study on Amazons Mechanical Turk; half were randomly assigned to visit alz.org, while a control group did not. Both groups were given the AD Knowledge Scale (ADKS) to assess their knowledge of AD. Results: Participants who visited alz.org scored significantly higher on the ADKS than those in the control group. Participants who were health care workers demonstrated higher scores than others in the experimental condition. Findings indicate that the Alzheimers Association Web site is effective at producing higher scores for AD knowledge relative to no Web site at all and that it is especially helpful for health care workers compared to those who are not health care workers.


Author Keywords
ADKS;  Alzheimer's Association;  Alzheimer's disease;  Alzheimer's Disease Knowledge Scale;  dementia

 


Document Type: Article
Source: Scopus

 

 

February 20, 2015

Cantoni, C.a , Bollman, B.a , Licastro, D.b , Xie, M.c , Mikesell, R.a , Schmidt, R.c , Yuede, C.M.a , Galimberti, D.d , Olivecrona, G.e , Klein, R.S.f , Cross, A.H.a , Otero, K.g , Piccio, L.a
TREM2 regulates microglial cell activation in response to demyelination in vivo
(2015) Acta Neuropathologica, 19 p. Article in Press. 


a Department of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8111St Louis, MO, United States
b CBM Scrl -Genomics, Area Science Park, BasovizzaTrieste, Italy
c Department of Pathology and Immunology, Washington University School of MedicineSt Louis, MO, United States
d Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale PoliclinicoMilan, Italy
e Department of Medical Biosciences/Physiological Chemistry, Umeå UniversityUmeå, Sweden
f Department of Medicine, Washington University School of MedicineSt Louis, MO, United States
g Immunology Research, Biogen Idec, 12 Cambridge CenterCambridge, MA, United States


Abstract
Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2−/−) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2−/− microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2−/− microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage.


Author Keywords
Cuprizone-induced demyelination;  Microglia;  Phagocytosis;  TREM2


Document Type: Article in Press
Source: Scopus




Lenze, S.N., Rodgers, J., Luby, J.
A pilot, exploratory report on dyadic interpersonal psychotherapy for perinatal depression
(2015) Archives of Women's Mental Health, 7 p. Article in Press. 


Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 S. EuclidSt. Louis, MO, United States


Abstract
Perinatal depression is a major public health burden impacting both mothers and their offspring. The purpose of this study was to develop and test the acceptability and feasibility of a novel psychotherapeutic intervention that integrates an evidence-based intervention for depression, interpersonal psychotherapy (IPT), with postpartum dyadic psychotherapy focused on emotional development in the context of the mother-infant relationship. Nine women between 12 and 30 weeks gestation with Edinburgh Depression Scale (EDS) scores >12 were entered into treatment. Three out of nine women dropped out of the study after initiating treatment (one lost to follow-up antepartum; two lost to follow-up postpartum). Seven out of eight women (87 %) reported clinically significant improvements in EDS scores from baseline to 37–39 weeks gestation, and all women had clinically significant improvements at 12 months postpartum. A small randomized controlled trial is underway to further examine the feasibility and acceptability of the intervention.


Author Keywords
Depression;  Interpersonal psychotherapy;  Mother-infant interactions;  Postpartum;  Pregnancy


Document Type: Article in Press
Source: Scopus




Lanier, P.a b , Kohl, P.L.b c , Raghavan, R.b c , Auslander, W.b c
A Preliminary Examination of Child Well-Being of Physically Abused and Neglected Children Compared to a Normative Pediatric Population
(2015) Child Maltreatment, 20 (1), pp. 72-79. 


a School of Social Work, University of North Carolina at Chapel HillChapel Hill, NC, United States
b Brown Center for Violence and Injury Prevention, Washington University in St. LouisSt. Louis, MO, United States
c Brown School of Social Work, Washington University in St. LouisSt. Louis, MO, United States


Abstract
Federal mandates require state child welfare systems to monitor and improve outcomes for children in three areas: safety, permanency, and well-being. Research across separate domains of child well-being indicates maltreated children may experience lower pediatric health–related quality of life (HRQL). This study assessed well-being in maltreated children using the Pediatric Quality of Life Inventory (PedsQL 4.0), a widely used measure of pediatric HRQL. The PedsQL 4.0 was used to assess well-being in a sample of children (N = 129) receiving child welfare services following reports of alleged physical abuse or neglect. We compared total scores and domain scores for this maltreated sample to those of a published normative sample. Within the maltreated sample, we also compared well-being by child and family demographic characteristics. As compared with a normative pediatric population, maltreated children reported significantly lower total, physical, and psychosocial health. We found no significant differences in total and domain scores based on child and parent demographics within the maltreated sample. This preliminary exploration indicates children receiving child welfare services have significantly lower well-being status than the general child population and have considerable deficits in social and emotional functioning. These findings support continued investment in maltreatment prevention and services to improve the well-being of victims of maltreatment.


Author Keywords
child maltreatment;  children in child welfare;  physical health


Document Type: Article
Source: Scopus




Fowler, P.J.a , Motley, D.b , Zhang, J.c , Rolls-Reutz, J.c , Landsverk, J.d
Adolescent Maltreatment in the Child Welfare System and Developmental Patterns of Sexual Risk Behaviors
(2015) Child Maltreatment, 20 (1), pp. 50-60. 


a Washington University in St. LouisSt. Louis, MO, United States
b DePaul UniversityChicago, IL, United States
c Rady Children’s HospitalSan Diego, CA, United States
d Oregon Social Learning CenterEugene, OR, United States


Abstract
In this longitudinal study, we tested whether adolescent maltreatment and out-of-home placement as a response to maltreatment altered developmental patterns of sexual risk behaviors in a nationally representative sample of youth involved in the child welfare system. Participants included adolescents aged 13 to 17 (M = 15.5, SD = 1.49) at baseline (n = 714), followed over 18 months. Computer-assisted interviews were used to collect self-reported sexual practices and experiences of physical and psychological abuse at both time points. Latent transition analyses were used to identify three patterns of sexual risk behaviors: abstainers, safe sex with multiple partners, and unsafe sex with multiple partners. Most adolescents transitioned to safer sexual behavior patterns over time. Adolescents exhibiting the riskiest sexual practices at baseline were most likely to report subsequent abuse and less likely to be placed into out-of-home care. Findings provide a more nuanced understanding of sexual risk among child welfare–involved adolescents and inform practices to promote positive transitions within the system.


Author Keywords
adolescent;  child maltreatment;  child welfare;  longitudinal;  sexual risk behavior


Document Type: Article
Source: Scopus




Helwani, M.A.a , Avidan, M.S.a , Ben Abdallah, A.a , Kaiser, D.J.a , Clohisy, J.C.b , Hall, B.L.c , Kaiser, H.A.a
Effects of regional versus general anesthesia on outcomes after total hip arthroplasty: A retrospective propensity-matched cohort study
(2015) Journal of Bone and Joint Surgery - American Volume, 97 (3), pp. 186-193. 


a Department of Anesthesiology, Washington University in St. Louis School of Medicine, 660 South Euclid AvenueSt. Louis, MO, United States
b Department of Orthopedic Surgery, Washington University in St. Louis School of Medicine, 660 South Euclid AvenueSt. Louis, MO, United States
c Department of Surgery, Washington University in St. Louis School of Medicine, 660 South Euclid AvenueSt. Louis, MO, United States


Abstract
Background: Many orthopaedic surgical procedures can be performed with either regional or general anesthesia. We hypothesized that total hip arthroplasty with regional anesthesia is associated with less postoperative morbidity and mortality than total hip arthroplasty with general anesthesia. Methods: This retrospective propensity-matched cohort study utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database included patients who had undergone total hip arthroplasty from 2007 through 2011. Aftermatching, logistic regression was used to determine the association between the type of anesthesia and deep surgical site infections, hospital length of stay, thirty-day mortality, and cardiovascular and pulmonary complications. Results: Of 12,929 surgical procedures, 5103 (39.5%) were performed with regional anesthesia. The adjusted odds for deep surgical site infections were significantly lower in the regional anesthesia group than in the general anesthesia group (odds ratio [OR] = 0.38; 95% confidence interval [CI] = 0.20 to 0.72; p < 0.01). The hospital length of stay (geometric mean) was decreased by 5% (95% CI = 3% to 7%; p < 0.001) with regional anesthesia, which translates to 0.17 day for each total hip arthroplasty. Regional anesthesia was also associated with a 27% decrease in the odds of prolonged hospitalization (OR = 0.73; 95% CI = 0.68 to 0.89; p < 0.001). The mortality rate was not significantly lower with regional anesthesia (OR = 0.78; 95% CI = 0.43 to 1.42; p > 0.05). The adjusted odds for cardiovascular complications (OR = 0.61; 95% CI = 0.44 to 0.85) and respiratory complications (OR = 0.51; 95% CI = 0.33 to 0.81) were all lower in the regional anesthesia group. Conclusions: Compared with general anesthesia, regional anesthesia for total hip arthroplasty was associated with a reduction in deep surgical site infection rates, hospital length of stay, and rates of postoperative cardiovascular and pulmonary complications. These findings could have an important medical and economic impact on health-care practice. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Document Type: Review
Source: Scopus




Speirs, C.K.a , Simpson, J.R.a , Robinson, C.G.a , Dewees, T.A.a , Tran, D.D.b , Linette, G.b , Chicoine, M.R.c , Dacey, R.G.c , Rich, K.M.c , Dowling, J.L.c , Leuthardt, E.C.c , Zipfel, G.J.c , Kim, A.H.c , Huang, J.a
Impact of 1p/19q codeletion and histology on outcomes of Anaplastic gliomas treated with radiation therapy and temozolomide
(2015) International Journal of Radiation Oncology Biology Physics, 91 (2), pp. 268-276. 


a Department of Radiation Oncology, Washington University, School of Medicine, 4921 Parkview Pl., Campus Box 8224St. Louis, MO, United States
b Department of Medicine, Division of Medical Oncology, Washington UniversitySt. Louis, MO, United States
c Department of Neurosurgery, Washington University, School of MedicineSt. Louis, MO, United States


Abstract
Purpose: Anaplastic gliomas represent a heterogeneous group of primary high-grade brain tumors, and the optimal postoperative treatment remains controversial. In this report, we present our institutional data on the clinical outcomes of radiation therapy (RT) plus temozolomide (RT + TMZ) for anaplastic gliomas, stratified by histology and 1p/19q codeletion. Methods and Materials: A single-institution retrospective review was conducted of patients with supratentorial anaplastic oligodendroglioma (AO), mixed anaplastic oligoastrocytoma (AOA), and anaplastic astrocytoma (AA). After surgery, RT was delivered at a median total dose of 60 Gy (range, 31.6-63 Gy) in daily fractions. All patients received standard concurrent TMZ, with or without adjuvant TMZ. Histological/molecular subtypes were defined as codeleted AO/AOA, non-codeleted AO/AOA, and AA. Results: From 2000 to 2012, 111 cases met study criteria and were evaluable. Codeleted AO/AOA had superior overall survival (OS) to non-codeleted AO/AOA (91% vs 68% at 5 years, respectively, P=.02), whereas progression-free survival (PFS) was not significantly different (70% vs 46% at 5 years, respectively, P=.10). AA had inferior OS to non-codeleted AO/AOA (37% vs 68% at 5 years, respectively, P=.007) and inferior PFS (27% vs 46%, respectively, PZ.03). On multivariate analysis, age, performance status, and histological or molecular subtype were independent predictors for both PFS and OS. Compared to historical controls, RT + TMZ provided comparable OS to RT with procarbazine, lomustine, and vincristine (RT + PCV) for codeleted AO/AOA, superior OS to RT alone for non-codeleted AO/AOA, and similar OS to RT alone for AA. Conclusions: RT + TMZ may be a promising treatment for both codeleted and noncodeleted AO/AOA, but its role for AA remains unclear.


Document Type: Article
Source: Scopus




Heaton, R.K.a , Franklin, D.R., Jr.a , Deutsch, R.a , Letendre, S.a , Ellis, R.J.a , Casaletto, K.a , Marquine, M.J.a , Woods, S.P.a , Vaida, F.a , Atkinson, J.H.a b , Marcotte, T.D.a , McCutchan, J.A.a , Collier, A.C.c , Marra, C.M.c , Clifford, D.B.d , Gelman, B.B.e , Sacktor, N.f , Morgello, S.g , Simpson, D.M.g , Abramson, I.a , Gamst, A.C.a , Fennema-Notestine, C.a , Smith, D.M.a , Grant, I.a
Neurocognitive change in the era of HIV combination antiretroviral therapy: The longitudinal CHARTER study
(2015) Clinical Infectious Diseases, 60 (3), pp. 473-480. Cited 1 time.


a University of CaliforniaSan Diego, CA, United States
b Veterans Affairs San Diego Healthcare SystemCA, United States
c University of WashingtonSeattle, United States
d Washington UniversitySt Louis, MO, United States
e University of Texas, Medical BranchGalveston, United States
f Johns Hopkins UniversityBaltimore, MD, United States
g Icahn School of Medicine at Mount SinaiNew York, NY, United States


Abstract
Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P <. 0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.


Author Keywords
antiretroviral therapy;  cognitive change;  comorbidities;  HIV


Document Type: Article
Source: Scopus




Greene, D.J.a b , Koller, J.M.b , Robichaux-Viehoever, A.c , Bihun, E.C.b , Schlaggar, B.L.a c d e , Black, K.J.a b c d
Reward enhances tic suppression in children within months of tic disorder onset
(2015) Developmental Cognitive Neuroscience, 11, pp. 65-74. 


a Department of Radiology, Washington University School of Medicine, United States Department of Radiology, United States
b Department of Psychiatry, Washington University School of Medicine, United States
c Department of Neurology, Washington University School of Medicine, United States
d Department of Anatomy and Neurobiology, Washington University School of Medicine, United States
e Department of Pediatrics, Washington University School of Medicine, United States


Abstract
Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic.


Author Keywords
Inhibitory control;  Reinforcement;  Reward;  Suppression;  Tics;  Tourette syndrome

 


Document Type: Article
Source: Scopus

 

February 13, 2015

Treiman, R.a , Decker, K.a , Kessler, B.a , Pollo, T.C.b
Variation and repetition in the spelling of young children
(2015) Journal of Experimental Child Psychology, 132, pp. 99-110. 


a Department of Psychology, Washington University in St. LouisSt. Louis, MO, United States
b Departamento de Psicologia, Universidade Federal de São João Del-ReiSão João Del-Rei, Brazil


Abstract
A number of investigators have suggested that young children, even those who do not yet represent the phonological forms of words in their spellings, tend to use different strings of letters for different words. However, empirical evidence that children possess a concept of between-word variation has been weak. In a study by Pollo, Kessler, and Treiman (2009), in fact, prephonological spellers were more likely to write different words in the same way than would be expected on the basis of chance, not less likely. In the current study, preschool-age prephonological and phonological spellers showed a tendency to repeat spellings and parts of spellings that they had recently used. However, even prephonological spellers (mean age. ~. 4. years 8. months) showed more repetition when spelling the same word twice in succession than when spelling different words. The results suggest that children who have not yet learned to use writing to represent the sounds of speech show some knowledge that writing represents words and, thus, should vary to show differences between them. The results further suggest that in spelling, as in other domains, children have a tendency to repeat recent behaviors.


Author Keywords
Between-word variation;  Phonology;  Priming;  Repetition;  Spelling;  Writing


Document Type: Article
Source: Scopus

Richard, C.D.a b , Tanenbaum, A.c d , Audit, B.e , Arneodo, A.e , Khalil, A.a b d , Frankel, W.N.a b f
SWDreader: A wavelet-based algorithm using spectral phase to characterize spike-wave morphological variation in genetic models of absence epilepsy
(2015) Journal of Neuroscience Methods, 242, pp. 127-140. 


a The Jackson LaboratoryBar Harbor, ME, United States
b Graduate School for Biomedical Sciences and Engineering, University of MaineOrono, ME, United States
c Department of Neurology, School of Medicine, Washington UniversitySt. Louis, MO, United States
d CompuMAINE Lab, Department of Mathematics, University of MaineOrono, ME, United States
e Laboratoire de Physique, CNRS UMR 5672, Université de Lyon, École Normale Supérieure de LyonLyon, France
f Tufts University School of Medicine, Sackler SchoolBoston, MA, United States


Abstract
Background: Spike-wave discharges (SWD) found in neuroelectrical recordings are pathognomonic to absence epilepsy. The characteristic spike-wave morphology of the spike-wave complex (SWC) constituents of SWDs can be mathematically described by a subset of possible spectral power and phase values. Morlet wavelet transform (MWT) generates time-frequency representations well-suited to identifying this SWC-associated subset. New method: MWT decompositions of SWDs reveal spectral power concentrated at harmonic frequencies. The phase relationships underlying SWC morphology were identified by calculating the differences between phase values at SWD fundamental frequency from the 2nd, 3rd, and 4th harmonics, then using the three phase differences as coordinates to generate a density distribution in a {360°. ×. 360°. ×. 360°} phase difference space. Strain-specific density distributions were generated from SWDs of mice carrying the Gria4, Gabrg2, or Scn8a mutations to determine whether SWC morphological variants reliably mapped to the same regions of the distribution, and if distribution values could be used to detect SWD. Comparison with existing methods: To the best of our knowledge, this algorithm is the first to employ spectral phase to quantify SWC morphology, making it possible to computationally distinguish SWC morphological subtypes and detect SWDs. Results/conclusions: Proof-of-concept testing of the SWDfinder algorithm shows: (1) a major pattern of variation in SWC morphology maps to one axis of the phase difference distribution, (2) variability between the strain-specific distributions reflects differences in the proportions of SWC subtypes generated during SWD, and (3) regularities in the spectral power and phase profiles of SWCs can be used to detect waveforms possessing SWC-like morphology.


Author Keywords
Absence epilepsy;  Fundamental frequency;  Harmonic analysis;  Morlet wavelet transform;  Morphology;  Mouse mutant;  Phase differences;  Seizure detection algorithm;  Spike-wave complex;  Spike-wave discharge


Document Type: Article
Source: Scopus

Ostendorf, A.P.a , Wong, M.a b
mTOR Inhibition in Epilepsy: Rationale and Clinical Perspectives
(2015) CNS Drugs, 9 p. Article in Press. 


a Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid AvenueSt. Louis, MO, United States
b The Hope Center for Neurological Disorders, Washington University School of Medicine, Box 8111, 660 South Euclid AvenueSt. Louis, MO, United States


Abstract
Despite a large number of available medical options, many individuals with epilepsy are refractory to existing therapies that mainly target neurotransmitter or ion channel activity. A growing body of preclinical data has uncovered a molecular pathway that appears crucial in many genetic and acquired epilepsy syndromes. The mammalian target of rapamycin (mTOR) pathway regulates a number of cellular processes required in the growth, metabolism, structure, and cell-cell interactions of neurons and glia. Rapamycin and similar compounds inhibit mTOR complex 1 and decrease seizures, delay seizure development, or prevent epileptogenesis in many animal models of mTOR hyperactivation. However, the exact mechanisms by which mTOR inhibition drives decreased seizure activity have not been completely determined. Nonetheless, these preclinical data have led to limited use in humans with epilepsy due to tuberous sclerosis complex and polyhydramnios, megalencephaly, and symptomatic epilepsy with promising results. Currently, larger controlled studies are underway using mTOR inhibitors in individuals with tuberous sclerosis complex and intractable epilepsy.


Document Type: Article in Press
Source: Scopus

Pruett, J.R., Jr.a , Kandala, S.a , Petersen, S.E.b c , Povinelli, D.J.d
Brief Report: Theory of Mind, Relational Reasoning, and Social Responsiveness in Children With and Without Autism: Demonstration of Feasibility for a Larger-Scale Study
(2015) Journal of Autism and Developmental Disorders, 9 p. Article in Press. 


a Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8134St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8111St. Louis, MO, United States
c Department of Psychology, Washington University, One Brookings DriveSt. Louis, MO, United States
d Department of Biology, University of Louisiana, P.O. Box 42451Lafayette, LA, United States


Abstract
Understanding the underpinnings of social responsiveness and theory of mind (ToM) will enhance our knowledge of autism spectrum disorder (ASD). We hypothesize that higher-order relational reasoning (higher-order RR: reasoning necessitating integration of relationships among multiple variables) is necessary but not sufficient for ToM, and that social responsiveness varies independently of higher-order RR. A pilot experiment tested these hypotheses in n = 17 children, 3–14, with and without ASD. No child failing 2nd-order RR passed a false belief ToM test. Contrary to prediction, Social Responsiveness Scale scores did correlate with 2nd-order RR performance, likely due to sample characteristics. It is feasible to translate this comparative cognition-inspired line of inquiry for full-scale studies of ToM, higher-order RR, and social responsiveness in ASD.


Author Keywords
Analogical reasoning;  Autism;  Cognition;  Relational reasoning;  Social responsiveness;  Theory of mind


Document Type: Article in Press
Source: Scopus

Maddox, G.B.a b , Balota, D.A.a
Retrieval practice and spacing effects in young and older adults: An examination of the benefits of desirable difficulty
(2015) Memory and Cognition, 15 p. Article in Press. 


a Washington University in St. LouisSt. Louis, MO, United States
b Rhodes College, 110 Clough HallMemphis, TN, United States


Abstract
In the present study, we examined how the function relating continued retrieval practice (e.g., one, three, or five tests) and long-term memory retention is modulated by desirable difficulty (R. A. Bjork, 1994). Of particular interest was how retrieval difficulty differed across young and older adults and across manipulations of lag (Exp. 1) and spacing (Exp. 2). To extend on previous studies, the acquisition phase response latency was used as a proxy for retrieval difficulty, and our analysis of final-test performance was conditionalized on acquisition phase retrieval success, to more directly examine the influence of desirable difficulty on retention. The results from Experiment 1 revealed that continued testing in the short-lag condition led to consistent increases in retention, whereas continued testing in the long-lag condition led to increasingly smaller benefits in retention for both age groups. The results from Experiment 2 revealed that repeated spaced testing enhanced retention relative to taking one spaced test, for both age groups; however, repeated massed testing only enhanced retention over taking one test for young adults. Across both experiments, the response latency results were overall consistent with an influence of desirable difficulty on retention. The discussion focuses on the role of desirable difficulty during encoding in producing the benefits of lag, spacing, and testing.


Author Keywords
Refreshing;  Retrieval practice aging;  Spacing effect;  Testing effect


Document Type: Article in Press
Source: Scopus

Hood, A.a c , Pulvers, K.a , Spady, T.J.b , Kliebenstein, A.a , Bachand, J.a
Anxiety mediates the effect of acute stress on working memory performance when cortisol levels are high: a moderated mediation analysis
(2015) Anxiety, Stress and Coping, 18 p. Article in Press. 


a Department of Psychology, California State University San Marcos, San Marcos, CA, 92096, USA
b Department of Biological Sciences, California State University San Marcos, San Marcos, CA, 92096, USA
c Department of Psychology, Washington University in St Louis, St Louis, MO, 63130, USA


Abstract
Background: Anxiety is an aversive emotional state characterized by perceived uncontrollability and hypervigilance to threat that can frequently cause disruptions in higher-order cognitive processes like working memory. The attentional control theory (ACT) predicts that anxiety negatively affects the working memory system. Design: This study tested the association between anxiety and working memory after the addition of stress and measured the glucocorticoid, cortisol. To better understand this relationship, we utilized a moderated mediation model. Methods: Undergraduate students from a public university (N = 103) self-reported their anxiety levels. Participants first completed a short-term memory test. During and after a forehead cold pressor task (stress vs. control procedure) participants completed a working memory test. Salivary cortisol was taken at baseline and after the last working memory test. Results: Overall, acute stress had no effect on working memory. However, we found that anxiety levels mediated the influence of condition (stressed vs. control) on working memory, but only among those individuals who had high cortisol levels after exposure to acute stress, supporting a moderated mediation model. Conclusions: These results imply that activation of the hypothalamic–pituitary–adrenal axis was necessary for working memory impairment in anxious individuals. These results provide support for the ACT.


Author Keywords
ACT;  BAI;  bootstrapping;  glucocorticoids;  mediation;  stress


Document Type: Article in Press
Source: Scopus

Foster, K.A.a , Bowland, S.E.b , Vosler, A.N.c
All the Pain Along with All the Joy: Spiritual Resilience in Lesbian and Gay Christians
(2015) American Journal of Community Psychology, 11 p. Article in Press. 


a College of Social Work, University of South Carolina, 29208Columbia, SC, United States
b School of Social Work, Eastern Washington UniversityCheney, WA, United States
c George Warren Brown School of Social Work, Washington University in St. LouisSt. Louis, MO, United States


Abstract
Resilience among lesbian and gay (LG) Christians has received limited attention. We present results from a qualitative study of 27 LG Christians, for whom religion had high salience. The study explored the process of integrating sexual orientation with spirituality. Moving from recognition of incongruence between faith and sexual orientation to integration was found to be a resilience-building process. Through descriptive and process approaches, we identified three primary pathways individuals used to integrate their faith and sexual orientation: transforming theological meaning; finding a safe-enough congregation; and finding an affirming congregation. Some worked for social justice within congregations as part of the resilience-building process. We discuss important decision points for LG Christians that included critical evaluation of extant and potential support systems, redefining scripture and tradition, and transforming communities. A model for LG Christian Spiritual Resilience is presented.


Author Keywords
Affirming congregations;  Christianity;  Gay;  Identity integration;  Lesbian;  Spiritual resilience


Document Type: Article in Press
Source: Scopus

Heaps, J.M.a , Sithinamsuwan, P.b , Paul, R.a , Lerdlum, S.e , Pothisri, M.d , Clifford, D.c , Tipsuk, S.k , Catella, S.f , Busovaca, E.g , Fletcher, J.L.K.k , Raudabaugh, B.h , Ratto-Kim, S.i j , Valcour, V.f , Ananworanich, J.i j , On Behalf Of The Search 007/011 Study Groupsl
Association between brain volumes and HAND in cART-naïve HIV+ individuals from Thailand
(2015) Journal of NeuroVirology, 8 p. Article in Press. 


a Missouri Institute of Mental Health, University of Missouri-St. LouisSt. Louis, MO, United States
b Department of Medicine, Division of Neurology, Phramongkutklao HospitalBangkok, Thailand
c Department of Neurology, Washington UniversitySt. Louis, MO, United States
d Chulalongkorn University HospitalBangkok, Thailand
e Faculty of Medicine, Chulalongkorn UniversityBangkok, Thailand
f Memory and Aging Center, UCSF Department of Neurology, University of CaliforniaSan Francisco, CA, United States
g Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Medical CenterNew York, NY, United States
h Columbia University School of NursingNew York, NY, United States
i U.S. Military HIV Research Program, Walter Reed Army Institute of Research Silver Spring, MD., Henry M. Jackson Foundation for the Advancement of Military MedicineBethesda, MD, United States
j SEARCH, The Thai Red Cross AIDS Research CenterBangkok, Thailand
k Memory and Aging Center, UCSF Department of Neurology, University of CaliforniaSan Francisco, CA, United States


Abstract
This study aimed to determine the effects of human immunodeficiency virus (HIV) on brain structure in HIV-infected individuals with and without HIV-associated neurocognitive disorders (HAND). Twenty-nine HIV-uninfected controls, 37 HIV+, treatment-naïve, individuals with HAND (HIV+HAND+; 16 asymptomatic neurocognitive impairment (ANI), 12 mild neurocognitive disorder (MND), and 9 HIV-associated dementia HAD), and 37 HIV+, treatment-naïve, individuals with normal cognitive function (HIV+HAND−) underwent magnetic resonance imaging (MRI) and neuropsychological assessment. The HIV-infected participants had a mean (SD) age of 35 (7) years, mean (interquartile range (IQR)) CD4 count of 221 (83–324), and mean (IQR) log10 plasma viral load of 4.81 (4.39–5.48). Six regions of interest were selected for analyses including total and subcortical gray matter, total white matter, caudate, corpus callosum, and thalamus. The HIV+/HAND+ group exhibited significantly smaller brain volumes compared to the HIV-uninfected group in subcortical gray and total gray matter; however, there were no statistically significant differences in brain volumes between the HIV+HAND+ and HIV+HAND− groups or between HIV+/HAND− and controls. CD4 count at time of combination antiretroviral therapy (cART) initiation was associated with total and subcortical gray matter volumes but not with cognitive measures. Plasma viral load correlated with neuropsychological performance but not brain volumes. The lack of significant differences in brain volumes between HIV+HAND+ and HIV+HAND− suggests that brain atrophy is not a sensitive measure of HAND in subjects without advanced immunosuppression. Alternatively, current HAND diagnostic criteria may not sufficiently distinguish patients based on MRI measures of brain volumes.


Author Keywords
Cognition;  HIV-associated neurocognitive disorder;  Neuroimaging;  Thailand


Document Type: Article in Press
Source: Scopus

Ostermann, J.a b , Njau, B.c , Mtuy, T.d , Brown, D.S.b e , Mühlbacher, A.b f , Thielman, N.a g
One size does not fit all: HIV testing preferences differ among high-risk groups in Northern Tanzania
(2015) AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV, 9 p. Article in Press. 


a Duke Global Health Institute, Duke University, Durham, NC, USA
b Center for Health Policy and Inequalities Research, Duke University, Durham, NC, USA
c Community Health Department, Kilimanjaro Christian Medical College, Moshi, Tanzania
d Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK
e Brown School, Washington University in St. Louis, St. Louis, Missouri, USA
f Institut Gesundheitsökonomie und Medizinmanagement, Hochschule Neubrandenburg, Neubrandenburg, Germany
g School of Medicine, Duke University, Durham, NC, USA


Abstract
In order to maximize the effectiveness of “Seek, Test, and Treat” strategies for curbing the HIV epidemic, new approaches are needed to increase the uptake of HIV testing services, particularly among high-risk groups. Low HIV testing rates among such groups suggest that current testing services may not align well with the testing preferences of these populations. Female bar workers and male mountain porters have been identified as two important high-risk groups in the Kilimanjaro Region of Tanzania. We used conventional survey methods and a discrete choice experiment (DCE), a preference elicitation method increasingly applied by economists and policy-makers to inform health policy and services, to analyze trade-offs made by individuals and quantify preferences for HIV testing services. Bivariate descriptive statistics were used to analyze differences in survey responses across groups. Compared to 486 randomly selected community members, 162 female bar workers and 194 male Kilimanjaro porters reported 2–3 times as many lifetime sexual partners (p < 0.001), but similar numbers of lifetime HIV tests (median 1–2 across all groups). For the DCE, participants' stated choices across 12,978 hypothetical HIV testing scenarios (422 female and 299 male participants × 9 choice tasks × 2 alternatives) were analyzed using gender-specific mixed logit models. Direct assessments and the DCE data demonstrated that barworkers were less likely to prefer home testing and were more concerned about disclosure issues compared with their community counterparts. Male porters preferred testing in venues where antiretroviral therapy was readily available. Both high-risk groups were less averse to traveling longer distances to test compared to their community counterparts. These results expose systematic differences in HIV testing preferences across high-risk populations compared to their community peers. Tailoring testing options to the preferences of high-risk populations should be evaluated as a means of improving uptake of testing in these populations.


Author Keywords
discrete choice experiment;  HIV diagnosis;  HIV testing;  preferences;  Tanzania


Document Type: Article in Press
Source: Scopus

Storm, B.C.a , Angello, G.b , Buchli, D.R.c , Koppel, R.H.d , Little, J.L.e , Nestojko, J.F.e
A review of retrieval-induced forgetting in the contexts of learning, eyewitness memory, social cognition, autobiographical memory, and creative cognition
(2015) Psychology of Learning and Motivation - Advances in Research and Theory, 62, pp. 141-194. 


a Department of Psychology, University of CaliforniaSanta Cruz, CA, United States
b Department of Psychology, Texas A and M UniversityCollege Station, TX, United States
c Department of Psychology, University of CaliforniaLos Angeles, CA, United States
d Department of Psychology, University of Illinois at ChicagoChicago, IL, United States
e Department of Psychology, Washington University in St. LouisSt. Louis, MO, United States


Abstract
Retrieving information from memory can cause the forgetting of other information in memory, a phenomenon referred to as retrieval-induced forgetting. Over the past 20years, retrieval-induced forgetting has been observed in a variety of experimental contexts and has been argued to impact a number of cognitive and psychological processes. Not simply a laboratory phenomenon, retrieval-induced forgetting appears to have important implications for furthering our basic understanding of memory and behavior. In the present chapter, we provide a selective review of retrieval-induced forgetting in five contexts-learning and education, eyewitness memory, social cognition, autobiographical memory, and creative cognition-and discuss the importance of studying retrieval-induced forgetting in situations beyond the typical retrieval-practice paradigm.


Author Keywords
Autobiographical memory;  Creative cognition;  Eyewitness memory;  Memory;  Retrieval-induced forgetting;  Social cognition;  Testing effects


Document Type: Article
Source: Scopus

Dick, D.M.a , Agrawal, A.b , Keller, M.C.c , Adkins, A.a , Aliev, F.a , Monroe, S.d , Hewitt, J.K.b , Kendler, K.S.a , Sher, K.J.e
Candidate Gene–Environment Interaction Research: Reflections and Recommendations
(2015) Perspectives on Psychological Science, 10 (1), pp. 37-59. 


a Department of Psychiatry, Virginia Commonwealth University, United States
b Department of Psychiatry, Washington University in St. Louis, United States
c Institute for Behavioral Genetics, University of Colorado Boulder, United States
d Department of Psychology, University of Notre Dame, United States
e Department of Psychological Sciences, University of Missouri, United States


Abstract
Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing the understanding of the development of psychopathology. It represents a clear theoretical advance over studying these factors in isolation. However, research at the intersection of multiple fields creates many challenges. We review several reasons why the rapidly expanding candidate gene–environment interaction (cG×E) literature should be considered with a degree of caution. We discuss lessons learned about candidate gene main effects from the evolving genetics literature and how these inform the study of cG×E. We review the importance of the measurement of the gene and environment of interest in cG×E studies. We discuss statistical concerns with modeling cG×E that are frequently overlooked. Furthermore, we review other challenges that have likely contributed to the cG×E literature being difficult to interpret, including low power and publication bias. Many of these issues are similar to other concerns about research integrity (e.g., high false-positive rates) that have received increasing attention in the social sciences. We provide recommendations for rigorous research practices for cG×E studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes.


Author Keywords
candidate genes;  genetics;  gene–environment interaction;  G×E


Document Type: Article
Source: Scopus

Kamath, A.A., Limbrick, D.L., Smyth, M.D.
Characterization of postoperative fevers after hemispherotomy
(2014) Child's Nervous System, 31 (2), 6 p. 


Department of Neurological Surgery, St. Louis Children’s Hospital, Washington University School of Medicine, One Children’s Place, Suite 4S20St. Louis, MO, United States


Abstract
Objective: Patients who have undergone hemispherotomy for intractable epilepsy tend to develop postoperative fevers, which can be severe and/or prolonged, for unclear reasons. The purpose of this paper is to characterize postoperative fever curves after hemispherotomy based on factors including seizure etiology, perioperative blood loss, and the presence or absence of ventricular drainage.

Methods: We present 72 patients who underwent hemispherotomy at our institution between 1995 and 2013 by four surgeons. Data including daily maximum body temperature, seizure etiology, ventricular drain use, steroid and antipyretic use, and seizure control were gathered retrospectively based on electronic records including operative summaries, nursing notes, discharge summaries, and follow-up clinic notes.

Results: Seventy-two patients from 11 weeks to 21 years old (mean 7.4 years old) underwent hemispherotomy between 1995 and 2013. Sixty (83 %) had fevers postoperatively, while the remainder were afebrile. Patients without external ventricular drains had higher and more prolonged fevers compared to those with drains (p = 0.003). Patients with Rasmussen’s encephalitis tended to have higher postoperative fevers than patients with other seizure etiologies (p = 0.005), while patients with cortical dysplasia and polymicrogyria tended to have less severe fevers (p = 0.027 and 0.017, respectively). Fifty-five patients (76 %) had freedom from disabling seizures (Engel class I), and 96 % showed worthwhile improvement or better (Engel classes I–III).

Conclusion: Postoperative fever can be anticipated in hemispherotomy patients, may vary based on certain seizure etiologies, and may be mitigated by routinely utilizing external ventricular drainage. Hemispherotomy is an effective surgical procedure for intractable epilepsy in selected patients.


Author Keywords
Epilepsy;  Hemispherectomy;  Hemispherotomy;  Postoperative fever;  Ventriculostomy


Document Type: Article
Source: Scopus

Zhang, Y.a , Inder, T.E.b , Neil, J.J.c , Dierker, D.L.d , Alexopoulos, D.e , Anderson, P.J.f , Van Essen, D.C.d
Cortical structural abnormalities in very preterm children at 7years of age
(2015) NeuroImage, . Article in Press. 


a Division of Biomedical and Biological Science, Washington University School of Medicine, St Louis, MO, USA
b Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
c Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
d Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO, USA
e Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
f Clinical Sciences, Murdoch Children's Research Institute, Victoria, Australia


Abstract
We analyzed long-lasting alterations in brain morphometry associated with preterm birth using volumetric and surface-based analyses applied to children at age 7. years. Comparison of 24 children born very preterm (VPT) to 24 healthy term-born children revealed reductions in total cortical gray matter volume, white matter volume, cortical surface area and gyrification index. Regional cortical shape abnormalities in VPT children included the following: shallower anterior superior temporal sulci, smaller relative surface area in the inferior sensori-motor cortex and posterior superior temporal cortex, larger relative surface area and a cingulate sulcus that was shorter or more interrupted in medial frontoparietal cortex. These findings indicate a complex pattern of regional vulnerabilities in brain development that may contribute to the diverse and long-lasting neurobehavioral consequences that can occur after very premature birth.


Author Keywords
Cortical surface;  Folding;  MRI;  Relative surface area;  Structural abnormality;  Very preterm;  Volume


Document Type: Article in Press
Source: Scopus

Lachin, J.M.a , White, N.H.b , Hainsworth, D.P.c , Sun, W.a , Cleary, P.A.a , Nathan, D.M.d
Effect of intensive Diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC
(2015) Diabetes, 64 (2), pp. 631-642. Cited 1 time.


a George Washington UniversityRockville, MD, United States
b Washington UniversitySt. Louis, MO, United States
c University of MissouriColumbia, MO, United States
d Massachusetts General HospitalBoston, MA, United States


Abstract
The Diabetes Control and Complications Trial (DCCT) demonstrated that a mean of 6.5 years of intensive therapy aimed at near-normal glucose levels reduced the risk of development and progression of retinopathy by as much as 76% compared with conventional therapy. The Epidemiology of Diabetes Interventions and Complications study (EDIC) observational follow-up showed that the risk of further progression of retinopathy 4 years after the DCCT ended was also greatly reduced in the former intensive group, despite nearly equivalent levels of HbA1c, a phenomenon termed metabolic memory. Metabolic memory was shown to persist through 10 years of follow-up. We now describe the risk of further progression of retinopathy, progression to proliferative diabetic retinopathy, clinically significant macular edema, and the need for intervention (photocoagulation or anti-VEGF) over 18 years of follow-up in EDIC. The cumulative incidence of each retinal outcome continues to be lower in the former intensive group. However, the year-to-year incidence of these outcomes is now similar, owing in large part to a reduction in risk in the former conventional treatment group.


Document Type: Article
Source: Scopus

Pekmezci, M.a , Reuss, D.E.b , Hirbe, A.C.c , Dahiya, S.d , Gutmann, D.H.e , Von Deimling, A.b , Horvai, A.E.f , Perry, A.a g
Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas
(2015) Modern Pathology, 28 (2), pp. 187-200. 


a Division of Neuropathology, Department of Pathology, University of California San Francisco, 505 Parnassus AvenueSan Francisco, CA, United States
b Department Neuropathology, German Cancer Consortium (DKTK), University of HeidelbergHeidelberg, Germany
c Division of Medical Oncology, Department of Medicine, Washington University School of MedicineSt Louis, MO, United States
d Department of Pathology and Immunology, Washington University School of MedicineSt Louis, MO, United States
e Department of Neurology, Washington University School of MedicineSt Louis, MO, United States
f Department of Pathology, University of California San FranciscoSan Francisco, CA, United States
g Department of Neurological Surgery, University of California San FranciscoSan Francisco, CA, United States


Abstract
Cellular schwannoma is an uncommon, but well-recognized, benign peripheral nerve sheath tumor, which can be misdiagnosed as malignant peripheral nerve sheath tumor. To develop consensus diagnostic criteria for cellular schwannoma, we reviewed 115 malignant peripheral nerve sheath tumor and 26 cellular schwannoma cases from two institutions. Clinical data were retrieved from the electronic medical records, and morphologic features, maximal mitotic counts, Ki67 labeling indices, and immunohistochemical profiles (SOX10, SOX2, p75NTR, p16, p53, EGFR, and neurofibromin) were assessed. Several features distinguish cellular schwannoma from malignant peripheral nerve sheath tumor. First, in contrast to patients with malignant peripheral nerve sheath tumor, no metastases or disease-specific deaths were found in patients with cellular schwannoma. More specifically, 5-year progression-free survival rates were 100 and 18%, and 5-year disease-specific survival rates were 100 and 32% for cellular schwannoma and malignant peripheral nerve sheath tumor, respectively. Second, the presence of Schwannian whorls, a peritumoral capsule, subcapsular lymphocytes, macrophage-rich infiltrates, and the absence of fascicles favored the diagnosis of cellular schwannoma, while the presence of perivascular hypercellularity, tumor herniation into vascular lumens, and necrosis favor malignant peripheral nerve sheath tumor. Third, complete loss of SOX10, neurofibromin or p16 expression, or the presence of EGFR immunoreactivity was specific for malignant peripheral nerve sheath tumor (P<0.001 for each). Expression of p75NTR was observed in 80% of malignant peripheral nerve sheath tumors compared with 31% of cellular schwannomas (P<0.001). Fourth, Ki-67 labeling indices ≥20% were highly predictive of malignant peripheral nerve sheath tumor (87% sensitivity and 96% specificity). Taken together, the combinations of these histopathological and immunohistochemical features provide useful criteria to distinguish between malignant peripheral nerve sheath tumor and cellular schwannoma with high sensitivity and specificity. Additional retrospective and prospective multicenter studies with larger data sets will be required to validate these findings.


Document Type: Review
Source: Scopus

Kulke, M.H.a , Shah, M.H.b , Benson, A.B., IIIc , Bergsland, E.d , Berlin, J.D.e , Blaszkowsky, L.S.f , Emerson, L.g , Engstrom, P.F.h , Fanta, P.i , Giordano, T.j , Goldner, W.S.k , Halfdanarson, T.R.l , Heslin, M.J.m , Kandeel, F.n , Kunz, P.L.o , Kuvshinoff, B.W., IIp , Lieu, C.q , Moley, J.F.r , Munene, G.s , Pillarisetty, V.G.t , Saltz, L.u , Sosa, J.A.v , Strosberg, J.R.w , Vauthey, J.-N.x , Wolfgang, C.y , Yao, J.C.x , Burns, J.z , Freedman-Cass, D.z
Neuroendocrine tumors, version 1.2015
(2015) JNCCN Journal of the National Comprehensive Cancer Network, 13 (1), pp. 78-108. 


a Dana-Farber/Brigham and Women's Cancer Center, United States
b Ohio State University Comprehensive Cancer Center, James Cancer Hospital, Solove Research Institute, United States
c Robert H. Lurie Comprehensive Cancer Center, Northwestern University, United States
d UCSF Helen Diller Family Comprehensive Cancer Center, United States
e Vanderbilt-Ingram Cancer Center, United States
f Massachusetts General Hospital Cancer Center, United States
g Huntsman Cancer Institute, University of Utah, United States
h Fox Chase Cancer Center, United States
i UC San Diego Moores Cancer Center, United States
j University of Michigan Comprehensive Cancer Center, United States
k Fred and Pamela Buffett Cancer Center, Nebraska Medical Center, United States
l Mayo Clinic Cancer Center, United States
m University of Alabama, Birmingham Comprehensive Cancer Center, United States
n City of Hope Comprehensive Cancer Center, United States
o Stanford Cancer Institute, United States
p Roswell Park Cancer Institute, United States
q University of Colorado Cancer Center, United States
r Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, United States
s St. Jude Children's Research Hospital, University of Tennessee Health Science Center, United States
t University of Washington, Seattle Cancer Care Alliance, United States
u Memorial Sloan Kettering Cancer Center, United States
v Duke Cancer Institute, United States
w Moffitt Cancer Center, United States
x University of Texas MD Anderson Cancer Center, United States
y Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, United States
z NCCN, United States


Abstract
Neuroendocrine tumors (NETs) comprise a broad family of tumors that may or may not be associated with symptoms attributable to hormonal hypersecretion. The NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine Tumors discuss the diagnosis and management of both sporadic and hereditary NETs. This selection from the guidelines focuses on sporadic NETs of the pancreas, gastrointestinal tract, lung, and thymus.


Document Type: Article
Source: Scopus

Baker, M.G.a , Criswell, S.R.b , Racette, B.A.b c , Simpson, C.D.a , Seixas, N.S.a d , Checkoway, H.e , Sheppard, L.a
Neurological outcomes associated with low-level manganese exposure in an inception cohort of asymptomatic welding trainees
(2015) Scandinavian Journal of Work, Environment and Health, 41 (1), pp. 94-101. 


a Department of Environmental and Occupational Health Sciences, University of WashingtonSeattle, DE, United States
b Department of Neurology, Washington University School of MedicineSt. Louis, MT, United States
c Faculty of Health Sciences, School of Public Health, University of WitwatersrandJohannesburg, South Africa
d Department of Biostatistics, University of WashingtonSeattle, DE, United States
e Department of Family and Preventive Medicine, University of California San DiegoSan Diego, CA, United States


Abstract
Objective Long-term, high-level exposure to manganese (Mn) is associated with impaired central nervous system (CNS) function. We quantitatively explored relations between low-level Mn exposure and selected neurological outcomes in a longitudinal inception cohort of asymptomatic welder trainees. Methods Welders with no previous occupational Mn exposure were observed approximately every three months over the course of the five-quarter traineeship. Fifty-six welders were assessed for motor function using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) and Grooved Pegboard tests. A subset of 17 also had MRI scans to assess T1-weighted indices. Personal exposure to Mn in welding fume was quantitatively assessed during the study period using a mixed model to obtain estimates of subject-specific exposure level by welding type. These estimates were summed to estimate cumulative exposure at the time of each neurological outcome test. Results When adjusting for possible learning effects, there were no associations between cumulative exposure and UPDRS3 score or Grooved Pegboard time. T1-weighted indices of the basal ganglia (caudate, anterior putamen, posterior putamen, and combined basal ganglia, but not the pallidal index) exhibited statistically significant increases in signal intensity in relation to increased cumulative Mn exposure. Conclusions This study demonstrates that T1-weighted changes can be detected in the brain even at very low levels of exposure among humans before any clinically evident deficits. This suggests that with continued followup we could identify a T1 threshold of toxicity at which clinical symptoms begin to manifest


Author Keywords
Biomarker of effect;  Biomarker of exposure;  Effect;  Exposure;  Grooved pegboard;  Learning effect;  MRI;  UPDRS3;  Welder


Document Type: Article
Source: Scopus

Rempel, D.a , Gerr, F.b , Harris-Adamson, C.a , Hegmann, K.T.c , Thiese, M.S.c , Kapellusch, J.d , Garg, A.d , Burt, S.e , Bao, S.f , Silverstein, B.f , Merlino, L.b , Dale, A.M.g , Evanoff, B.g
Personal and workplace factors and median nerve function in a pooled study of 2396 US workers
(2015) Journal of Occupational and Environmental Medicine, 57 (1), pp. 98-104. 


a Division of Occupational and Environmental Medicine, University of California at San Francisco, 1301 South 46th St Bldg 163Richmond, CA, United States
b Department of Occupational and Environmental Health, College of Public Health, University of Iowa, United States
c Rocky Mountain Center for Occupational and Environmental Health, University of UtahSalt Lake City, United States
d Department of Occupational Science and Technology, University of Wisconsin-Milwaukee, United States
e National Institute for Occupational Safety and HealthCincinnati, OH, United States
f Safety and Health Assessment and Research for Prevention Program, Washington State Department of Labor and IndustriesOlympia, United States
g Division of General Medical Science (Drs Dale and Evanoff), Washington University, School of MedicineSaint Louis, United States


Abstract
OBJECTIVE:: Evaluate associations between personal and workplace factors and median nerve conduction latency at the wrist. METHODS:: Baseline data on workplace psychosocial and physical exposures were pooled from four prospective studies of production and service workers (N = 2396). During the follow-up period, electrophysiologic measures of median nerve function were collected at regular intervals. RESULTS:: Significant adjusted associations were observed between age, body mass index, sex, peak hand force, duration of forceful hand exertions, Threshold Limit Value for Hand Activity Limit, forceful repetition rate, wrist extension, and decision latitude on median nerve latencies. CONCLUSIONS:: Occupational and nonoccupational factors have adverse effects on median nerve function. Measuring median nerve function eliminates possible reporting bias that may affect symptom-based carpal tunnel syndrome case definitions. These results suggest that previously observed associations between carpal tunnel syndrome and occupational factors are not the result of such reporting bias.


Document Type: Article
Source: Scopus

Akbari, S.H.A.a , Holekamp, T.F.a , Murphy, T.M.a , Mercer, D.a , Leonard, J.R.c d , Smyth, M.D.a b , Park, T.S.a b , Limbrick, D.D., Jr.a b
Surgical management of complex multiloculated hydrocephalus in infants and children
(2014) Child's Nervous System, 31 (2), 7 p. 


a Department of Neurological Surgery, St. Louis Children’s Hospital, Washington University School of Medicine, Washington University in St. Louis, One Children’s Place, Suite 4S20St. Louis, MO, United States
b Department of Pediatrics, St. Louis Children’s Hospital, Washington University School of Medicine, Washington University in St. LouisSt. Louis, MO, United States
c Department of Neurosurgery, Nationwide Children’s Hospital, The Ohio State University College of Medicine, The Ohio State UniversityColumbus, OH, United States
d Department of Neurosciences, Nationwide Children’s Hospital, The Ohio State University College of Medicine, The Ohio State UniversityColumbus, OH, United States


Abstract
Objective: Multiloculated hydrocephalus may occur as a consequence of intraventricular hemorrhage or infection and is characterized by enlargement of multiple noncommunicating intraventricular and/or periventricular cysts. In this study, we report the outcomes of open and endoscopic fenestration for multiloculated hydrocephalus at our institution.

Methods: Records of children who underwent endoscopic or open fenestration at St. Louis Children’s Hospital from 1999 to 2011 were analyzed. The cause of MLH, operative parameters, length of hospital stay, and subsequent shunt intervention rate were recorded.

Results: Twenty-five subjects were identified for study. Twelve subjects underwent open craniotomy and 13 underwent endoscopic fenestration. Endoscopic fenestration was associated with decreased blood loss, operative time, and length of stay (p = 0.003, 0.002, 0.02, respectively). Subjects undergoing craniotomy had an average of 5.1 ± 4.5 subsequent shunt-related interventions versus 3.1 ± 4.0 in the endoscopy group (p = 0.25). The craniotomy group’s median subsequent shunt revision rate was 0.74 interventions per year versus 0.50 interventions per year in the endoscopy group (p = 0.51). Fifty percent of subjects in the open fenestration group required additional fenestration surgery compared to 38.5 % in the endoscopic group (p = 0.70).

Conclusion: Both open and endoscopic fenestration appeared effective at improving shunt management. The endoscopic technique may offer advantages in operative time, blood loss, and length of hospital stay. These data suggest that endoscopic fenestration may be used as the initial approach for treatment of multiloculated hydrocephalus, with craniotomy and open fenestration used for more severe or refractory cases.


Author Keywords
Cystic hydrocephalus;  Fenestration;  Intraventricular hemorrhage;  Loculated hydrocephalus;  Multiloculated hydrocephalus;  Ventriculitis


Document Type: Article
Source: Scopus

Del Brutto, O.H.a , Sedler, M.J.b , Mera, R.M.c , Lama, J.d , Gruen, J.A.b , Phelan, K.J.b , Cusick, E.H.b , Zambrano, M.e , Brown, D.L.f
The association of ankle-brachial index with silent cerebral small vessel disease: results of the Atahualpa Project
(2015) International Journal of Stroke, . Article in Press. 


a School of Medicine Universidad Espíritu Santo Guayaquil Ecuador
b School of Medicine Stony Brook University New York, NY USA
c Gastroenterology Department Vanderbilt University Nashville, TN USA
d Imaging Department Hospital-Clínica Kennedy Guayaquil Ecuador
e Community Center the Atahualpa Project. Atahualpa Ecuador
f Cardiovascular Division Washington University School of Medicine St. Louis, MO USA


Abstract
Background: An abnormal ankle-brachial index has been associated with overt stroke and coronary heart disease, but little is known about its relationship with silent cerebral small vessel disease. Aim: To assess the value of ankle-brachial index as a predictor of silent small vessel disease in an Ecuadorian geriatric population. Methods: Stroke-free Atahualpa residents aged ≥60 years were identified during a door-to-door survey. Ankle-brachial index determinations and brain magnetic resonance imaging were performed in consented persons. Ankle-brachial index ≤0·9 and ≥1·4 were proxies of peripheral artery disease and noncompressible arteries, respectively. Using logistic regression models adjusted for age, gender, and cardiovascular health status, we evaluated the association between abnormal ankle-brachial index with silent lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. Results: Mean age of the 224 participants was 70±8 years, 60% were women, and 80% had poor cardiovascular health status. Ankle-brachial index was ≤0·90 in 37 persons and ≥1·4 in 17. Magnetic resonance imaging showed lacunar infarcts in 27 cases, moderate-to-severe white matter hyperintensities in 47, and cerebral microbleeds in 26. Adjusted models showed association of lacunar infarcts with ankle-brachial index≤0·90 (OR: 3·72, 95% CI: 1·35-10·27, P=0·01) and with ankle-brachial index≥1·4 (OR: 3·85, 95% CI: 1·06-14·03, P=0·04). White matter hyperintensities were associated with ankle-brachial index≤0·90 (P=0·03) and ankle-brachial index≥1·4 (P=0·02) in univariate analyses. There was no association between ankle-brachial index groups and cerebral microbleeds. Conclusions: In this population-based study conducted in rural Ecuador, apparently healthy individuals aged ≥60 years with ankle-brachial index values ≤0·90 and ≥1·4 are almost four times more likely to have a silent lacunar infarct. Ankle-brachial index screening might allow recognition of asymptomatic people who need further investigation and preventive therapy.


Author Keywords
Ankle-brachial index;  Cerebral small vessel disease;  Peripheral artery disease;  Population-based study;  Silent lacunar strokes;  White matter hyperintensities


Document Type: Article in Press
Source: Scopus

Brandon Westover, M.a b , Ching, S.c , Kumaraswamy, V.M.a , Akeju, O.d , Pierce, E.d e , Cash, S.S.a b , Kilbride, R.f , Brown, E.N.d e g , Purdon, P.L.d e g
The human burst suppression electroencephalogram of deep hypothermia
(2015) Clinical Neurophysiology, . Article in Press. 


a Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
b Department of Neurology, Harvard Medical School, Boston, MA, USA
c Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
d Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
e Department of Anaesthesiology, Harvard Medical School, Boston, MA, USA
f Department of Neurology, Beaumont Hospital, Dublin, Ireland
g Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA, USA


Abstract
Objective: Deep hypothermia induces 'burst suppression' (BS), an electroencephalogram pattern with low-voltage 'suppressions' alternating with high-voltage 'bursts'. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity. Methods: We recorded scalp electroencephalograms from eleven patients undergoing deep hypothermia during cardiac surgery with complete circulatory arrest, and analyzed these using methods of spectral analysis. Results: Within patients, the depth of BS systematically depends on the depth of hypothermia, though responses vary between patients except at temperature extremes. With decreasing temperature, burst lengths increase, and burst amplitudes and lengths decrease, while the spectral content of bursts remains constant. Conclusions: These findings support an existing theoretical model in which the common mechanism of burst suppression across diverse etiologies is the cyclical diffuse depletion of metabolic resources, and suggest the new hypothesis of local micro-network dropout to explain decreasing burst amplitudes at lower temperatures. Significance: These results pave the way for accurate noninvasive tracking of brain metabolic state during surgical procedures under deep hypothermia, and suggest new testable predictions about the network mechanisms underlying burst suppression.


Author Keywords
Burst suppression;  Electroencephalogram;  Hypothermia

Document Type: Article in Press
Source: Scopus