“Modafinil in Recovery after Stroke (MIRAS): A Retrospective Study” (2020) Journal of Stroke and Cerebrovascular Diseases
Modafinil in Recovery after Stroke (MIRAS): A Retrospective Study
(2020) Journal of Stroke and Cerebrovascular Diseases, 29 (4), art. no. 104645, .
Cross, D.B.a , Tiu, J.c , Medicherla, C.a , Ishida, K.a , Lord, A.a , Czeisler, B.a , Wu, C.a , Golub, D.a , Karoub, A.b , Hernandez, C.a , Yaghi, S.a , Torres, J.a
a NYU Langone Health, Department of Neurology, New York, NY, United States
b University of Michigan Medical School, Ann Arbor, MI, United States
c Washington University in St. Louis, St. Louis, MO, United States
Abstract
Background and Purpose: Acute rehabilitation is known to enhance stroke recovery. However, poststroke lethargy and fatigue can hinder participation in rehabilitation therapies. We hypothesized that in patients with moderate to severe stroke complicated by poststroke fatigue and lethargy early stimulant therapy with modafinil increases favorable discharge disposition defined as transfer to acute inpatient rehabilitation or home. Methods: We retrospectively reviewed a cohort of patients with acute stroke admitted to the stroke service over a 3-year period. All patients 18 years or older with confirmed ischemic or hemorrhagic stroke, an NIHSS greater than or equal to 5 and documentation of fatigue/lethargy in clinical documentation were included. We compared patients that were treated with modafinil 50-200 mg to those managed with standard care. The primary outcome measure was discharge disposition. Secondary outcome was 90 day modified Rankin score (mRS). Statistical significance was determined using chi-square test for association and logistic regression models. Logistic regression models were derived in 2 ways with both raw data and an adjusted model that accounted for age, sex, and NIHSS score to account for the lack of randomization. Results: This study included 199 stroke patients (145 ischemic, 54 hemorrhagic). Seventy-two (36.2%) were treated with modafinil and 129 (64.8%) were discharged to acute inpatient rehabilitation, while none were recommended for discharge home. Median NIHSS for modafinil patients was 13.5 versus 11 for standard care patients (P =.059). In adjusted models, modafinil was associated with higher odds of favorable discharge disposition (OR 2.00, 95% CI 1.01-3.95). Favorable outcome at 90 days defined as mRS less than or equal to 2 occurred more frequently with modafinil (5.6% versus 3.3%) but this did not achieve statistical significance (P >.1). These results occurred despite the modafinil group requiring longer ICU stays and having more in-hospital complications such as infections and need for percutaneous gastrostomy tubes. The benefit of modafinil was seen across all subgroups except those with severe stroke (NIHSS ≥ 15). There were no significant adverse events associated with modafinil administration. Conclusions: Modafinil use in acute in-hospital stroke patients with moderate stroke complicated by lethargy and fatigue was associated with improved discharge disposition. Randomized controlled trials are needed to further study the safety, efficacy, and long-term effects of modafinil in this patient population. © 2020 Elsevier Inc.
Author Keywords
Fatigue; modafinil; rehabilitation; stroke
Document Type: Article
Publication Stage: Final
Source: Scopus
“Quantitative Characterization of the Neuropeptide Level Changes in Dorsal Horn and Dorsal Root Ganglia Regions of the Murine Itch Models” (2020) Journal of Proteome Research
Quantitative Characterization of the Neuropeptide Level Changes in Dorsal Horn and Dorsal Root Ganglia Regions of the Murine Itch Models
(2020) Journal of Proteome Research, 19 (3), pp. 1248-1257.
Tillmaand, E.G., Anapindi, K.D.B., De La Toba, E.A., Guo, C.J., Krebs, J., Lenhart, A.E., Liu, Q., Sweedler, J.V.
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Chronic itch can be extremely devastating and, in many cases, difficult to treat. One challenge in treating itch disorders is the limited understanding of the multitude of chemical players involved in the communication of itch sensation from the peripheral to the central nervous system. Neuropeptides are intercellular signaling molecules that are known to be involved in the transmission of itch signals from primary afferent neurons, which detect itch in the skin, to higher-order circuits in the spinal cord and brain. To investigate the role of neuropeptides in transmitting itch signals, we generated two mouse models of chronic itch-Acetone-Ether-Water (AEW, dry skin) and calcipotriol (MC903, atopic dermatitis). For peptide identification and quantitation, we analyzed the peptide content of dorsal root ganglia (DRG) and dorsal horn (DH) tissues from chronically itchy mice using liquid chromatography coupled to tandem mass spectrometry. De novo-assisted database searching facilitated the identification and quantitation of 335 peptides for DH MC903, 318 for DH AEW, 266 for DRG MC903, and 271 for DRG AEW. Of these quantifiable peptides, we detected 30 that were differentially regulated in the tested models, after accounting for multiple testing correction (q ≤ 0.1). These include several peptide candidates derived from neuropeptide precursors, such as proSAAS, protachykinin-1, proenkephalin, and calcitonin gene-related peptide, some of them previously linked to itch. The peptides identified in this study may help elucidate our understanding about these debilitating disorders. Data are available via ProteomeXchange with identifier PXD015949.
Author Keywords
label-free quantitation; liquid chromatography; mass spectrometry; peptidomics; Skyline
Document Type: Article
Publication Stage: Final
Source: Scopus
“Glibenclamide reverses cardiovascular abnormalities of Cantu syndrome driven by KATP channel overactivity” (2020) Journal of Clinical Investigation
Glibenclamide reverses cardiovascular abnormalities of Cantu syndrome driven by KATP channel overactivity
(2020) Journal of Clinical Investigation, 130 (3), pp. 1116-1121. Cited 1 time.
McClenaghan, C.a b c , Huang, Y.a b c i , Yan, Z.a d , Harter, T.M.a b c , Halabi, C.M.a e , Chalk, R.f , Kovacs, A.g , Van Haaften, G.h , Remedi, M.S.a d , Nichols, C.G.a b c
a Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Cell Biology, Washington University School of Medicine, Saint Louis, MO, United States
c Department of Physiology, Washington University School of Medicine, Saint Louis, MO, United States
d Division of Endocrinology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, United States
e Division of Nephrology, Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, United States
f Structural Genomics Consortium, University of Oxford, Oxford, United Kingdom
g Department of Medicine, Washington University School of Medicine, Saint Louis, MO, United States
h Center for Molecular Medicine, Department of Genetics, University Medical Center Utrecht, Utrecht, Netherlands
i Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
Abstract
Cantu syndrome (CS) is a complex disorder caused by gain-of-function (GoF) mutations in ABCC9 and KCNJ8, which encode the SUR2 and Kir6.1 subunits, respectively, of vascular smooth muscle (VSM) KATP channels. CS includes dilated vasculature, marked cardiac hypertrophy, and other cardiovascular abnormalities. There is currently no targeted therapy, and it is unknown whether cardiovascular features can be reversed once manifest. Using combined transgenic and pharmacological approaches in a knockin mouse model of CS, we have shown that reversal of vascular and cardiac phenotypes can be achieved by genetic downregulation of KATP channel activity specifically in VSM, and by chronic administration of the clinically used KATP channel inhibitor, glibenclamide. These findings demonstrate that VSM KATP channel GoF underlies CS cardiac enlargement and that CS-associated abnormalities are reversible, and provide evidence of in vivo efficacy of glibenclamide as a therapeutic agent in CS. © 2020, American Society for Clinical Investigation.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Iterative image reconstruction in transcranial photoacoustic tomography based on the elastic wave equation” (2020) Physics in Medicine and Biology
Iterative image reconstruction in transcranial photoacoustic tomography based on the elastic wave equation
(2020) Physics in Medicine and Biology, 65 (5), p. 055009.
Poudel, J., Na, S., Wang, L.V., Anastasio, M.A.
Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Dr., St. Louis, MO 63130, United States of America
Abstract
Photoacoustic computed tomography (PACT) is an emerging computed imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the photoacoustically induced initial pressure distribution within tissue. The PACT reconstruction problem corresponds to a time-domain inverse source problem, where the initial pressure distribution is recovered from the measurements recorded on an aperture outside the support of the source. A major challenge in transcranial PACT of the brain is to compensate for aberrations and attenuation in the measured data due to the propagation of the photoacoustic wavefields through the skull. To properly account for these effects, a wave equation-based inversion method can be employed that can model the heterogeneous elastic properties of the medium. In this study, an optimization-based image reconstruction method for 3D transcranial PACT is developed based on the elastic wave equation. To accomplish this, a forward-adjoint operator pair based on a finite-difference time-domain discretization of the 3D elastic wave equation is utilized to compute penalized least squares estimates of the initial pressure distribution. Computer-simulation and experimental studies are conducted to investigate the robustness of the reconstruction method to model mismatch and its ability to effectively resolve cortical and superficial brain structures.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Designing Graphs for Decision-Makers” (2020) Policy Insights from the Behavioral and Brain Sciences
Designing Graphs for Decision-Makers
(2020) Policy Insights from the Behavioral and Brain Sciences, 7 (1), pp. 52-63.
Zacks, J.M.a , Franconeri, S.L.b
a Washington University in St. LouisMO, United States
b Northwestern University, Evanston, IL, United States
Abstract
Data graphics can be a powerful aid to decision-making—if they are designed to mesh well with human vision and understanding. Perceiving data values can be more precise for some graphical types, such as a scatterplot, and less precise for others, such as a heatmap. The eye can extract some types of statistics from large arrays in an eyeblink, as quickly as recognizing an object or face. But perceiving some patterns in visualized numbers—particularly comparisons within a dataset—is slow and effortful, unfolding over a series of operations that are guided by attention and previous experience. Effective data graphics map important messages onto visual patterns that are easily extracted, likely to be attended, and as consistent as possible with the audience’s previous experience. User-centered design methods, which rely on iteration and experimentation to improve a design, are critical tools for creating effective data visualizations. © The Author(s) 2019.
Author Keywords
data visualization; graphs; user-centered design; vision
Document Type: Article
Publication Stage: Final
Source: Scopus
“Early Childhood Trauma Impact on Adolescent Brain Development, Decision Making Abilities, and Delinquent Behaviors: Policy Implications for Juveniles Tried in Adult Court Systems” (2020) Juvenile and Family Court Journal
Early Childhood Trauma Impact on Adolescent Brain Development, Decision Making Abilities, and Delinquent Behaviors: Policy Implications for Juveniles Tried in Adult Court Systems
(2020) Juvenile and Family Court Journal, 71 (1), pp. 5-17.
Williams, A.
Brown school, Washington University in St. Louis, United States
Abstract
By examining previous literature on the brain’s developmental process during adolescence, this paper aims to determine how early childhood trauma potentially effects decision making in adolescence through exploring self-regulation theory. Through a self-regulation framework, the hope is to determine the connection, if any, between early childhood trauma, delinquent behavior, and involvement in the juvenile justice system. The author insists that not only do adolescents have less culpability due to their brain developmental stage compared to adults, but also early childhood trauma puts adolescents at a greater risk of impaired self-regulation which allows for more probable delinquent behavior. This paper also considers implications for social policy makers and youth advocates concerned with juvenile offenders tried in adult courts and existing racial disparities in the system. © 2020 National Council of Juvenile and Family Court Judges
Author Keywords
adolescent brain development; adverse childhood experiences; juvenile delinquency; juveniles tried in adult courts; policy; trauma
Document Type: Article
Publication Stage: Final
Source: Scopus
“Low burden strategies are needed to reduce smoking in rural healthcare settings: A lesson from cancer clinics” (2020) International Journal of Environmental Research and Public Health
Low burden strategies are needed to reduce smoking in rural healthcare settings: A lesson from cancer clinics
(2020) International Journal of Environmental Research and Public Health, 17 (5), art. no. 1728, .
Ramsey, A.T.a b , Baker, T.B.c , Pham, G.a , Stoneking, F.a , Smock, N.a , Colditz, G.A.b d , James, A.S.b d , Liu, J.b d , Bierut, L.J.a b , Chen, L.-S.a b
a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States
b Alvin J. Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Medicine, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53726, United States
d Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Rural populations face significant smoking-related health disparities, such as a higher prevalence of lung cancer and cancer mortality, higher prevalence of smoking, and lower likelihood of receiving cessation treatment than urban counterparts. A significant proportion of health disparities in rural populations could be eliminated with low-barrier, easy-access treatment delivery methods for smoking cessation. In this study, we assessed treatment engagement among patients in rural and urban settings. Then, we examined the effect of an electronic health record-based smoking cessation module on patient receipt of evidence-based cessation care. As part of a quality improvement project, we retrospectively observed 479,798 unique patients accounting for 1,426,089 outpatient clinical encounters from June 2018–March 2019 across 766 clinics in the greater St. Louis, southern Illinois, and mid-Missouri regions. Smoking prevalence was higher in rural versus urban clinics (20.7% vs. 13.9%, 6.7% [6.3, 7.1], odds ratio = 1.6 [1.6, 1.6], p < 0.0001), and yet rural smokers were nearly three times less likely than their urban counterparts to receive any smoking cessation treatment after adjusting for patients clustering within clinics (9.6% vs. 25.8%, −16.2% [−16.9, −15.5], odds ratio = 0.304 [0.28, 0.33], p < 0.0001). Although not yet scaled up in the rural setting, we examined the effects of a low-burden, point-of-care smoking module currently implemented in cancer clinics. After adjusting for patient clustering within clinics, patients were more likely to receive smoking treatment in clinics that implemented the module versus clinics that did not implement the module (31.2% vs. 17.5%, 13.7% [10.8, 16.6], odds ratio = 2.1 [1.8, 2.6], p < 0.0001). The point-of-care treatment approach offers a promising solution for rural settings, both in and outside the context of cancer care. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Cancer care; Decision support; Electronic health record; Health disparities; Implementation strategies; Rural; Smoking cessation treatment; Tobacco use
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Association of Blood Pressure With Outcomes in Acute Stroke Thrombectomy” (2020) Hypertension (Dallas, Tex. : 1979)
Association of Blood Pressure With Outcomes in Acute Stroke Thrombectomy
(2020) Hypertension (Dallas, Tex. : 1979), 75 (3), pp. 730-739.
Malhotra, K.a , Goyal, N.b , Katsanos, A.H.c , Filippatou, A.d , Mistry, E.A.e , Khatri, P.f , Anadani, M.g h , Spiotta, A.M.h , Sandset, E.C.i j , Sarraj, A.k , Magoufis, G.l , Krogias, C.m , Tönges, L.m , Safouris, A.l , Elijovich, L.n , Goyal, M.o , Arthur, A.n , Alexandrov, A.V.b , Tsivgoulis, G.b d
a From the Department of Neurology, Allegheny Health Network, Pittsburgh, United States
b Department of Neurology, University of Tennessee, A.V.A
c Department of Neurology, McMaster University/Population Health Research InstituteHamilton, Bermuda
d Second Department of Neurology, “Attikon” University Hospital, National and Kapodistrian University of Athens
e Department of Neurology, Vanderbilt University, Nashville, United States
f Department of Neurology, University of Cincinnati
g Department of Neurology, Washington University School of Medicine, St Louis, United States
h Department of Neurosurgery, Medical University of South Carolina
i Department of Neurology, Stroke Unit, Oslo University Hospital
j Norwegian Air Ambulance FoundationOslo, Norway
k Department of Neurology, UT Houston
l Stroke Unit, Metropolitan Hospital
m Department of Neurology, Ruhr-University Bochum, Germany (C.K., St. Josef-Hospital
n Department of Neurosurgery, University of Tennessee/Semmes-Murphey Clinic
o Departments of Radiology and Clinical Neurosciences, University of Calgary, AB
Abstract
Limited data exist evaluating the effect of blood pressure (BP) on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with mechanical thrombectomy (MT). We sought to evaluate the association of BP levels on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with MT. Studies were identified that reported the association of systolic BP (SBP) or diastolic BP levels before, during, or after MT on the outcomes of patients with acute ischemic stroke treated with MT. Unadjusted and adjusted analyses of studies reporting odds ratios (ORadj) per 10 mm Hg BP increment were performed. Our analysis included 25 studies comprising 6474 patients. Higher pre-MT mean SBP (P=0.008) and post-MT maximum SBP (P=0.009) levels were observed in patients who died within 3 months. Patients with 3-month functional independence were noted to have lower pre-MT (P<0.001) and post-MT maximum SBP levels (P<0.001). In adjusted analyses, increasing post-MT maximum SBP and diastolic BP levels were associated with 3-month mortality (ORadj, 1.19 [95% CI,1.00-1.43]; I2=78%, P value for Cochran Q test: 0.001) and symptomatic intracranial hemorrhage (ORadj, 1.65 [95% CI, 1.11-2.44]; I2=0%, P value for Cochran Q test: 0.80), respectively. Increasing pre- and post-MT mean SBP levels were associated with lower odds of 3-month functional independence (ORadj, 0.86 [95% CI, 0.77-0.96]; I2=18%, P value for Cochran Q test: 0.30) and (ORadj, 0.80 [95% CI, 0.72-0.89]; I2=0%, P value for Cochran Q test: 0.51), respectively. In conclusion, elevated BP levels before and after MT are associated with adverse outcomes among patients with acute ischemic stroke with large vessel occlusion.
Author Keywords
blood pressure; consensus; intracranial hemorrhages; odds ratio; thrombectomy
Document Type: Article
Publication Stage: Final
Source: Scopus
“Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism” (2020) The Journal of Clinical Endocrinology and Metabolism
Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism
(2020) The Journal of Clinical Endocrinology and Metabolism, 105 (3), .
Tahoun, M.a , Chandler, J.C.b , Ashton, E.c , Haston, S.b , Hannan, A.c , Kim, J.S.b , D’Arco, F.c , Bockenhauer, D.c , Anderson, G.c , Lin, M.-H.d , Marzouk, S.a , Saied, M.H.a , Miner, J.H.d , Dattani, M.T.b c , Waters, A.M.b c
a Clinical and Chemical Pathology Department, Faculty of Medicine, Alexandria University, Egypt
b UCL Great Ormond Street Institute of Child Health, University College London, United Kingdom
c Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom
d Division of Nephrology, Department of Medicine, Washington University School of Medicine, St Louis, MO, United States
Abstract
CONTEXT: Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome). CASE DESCRIPTION: This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel for steroid-resistant nephrotic syndrome, compound heterozygous missense mutations were identified in LAMB2 (c.737G>A p.Arg246Gln, c.3982G>C p.Gly1328Arg). Immunohistochemical analysis revealed reduced glomerular laminin β2 expression compared to control kidney and a thin basement membrane on electron microscopy. Laminin β2 is expressed during pituitary development and Lamb2-/- mice exhibit stunted growth, abnormal neural retinae, and here we show, abnormal parenchyma of the anterior pituitary gland. CONCLUSION: We propose that patients with genetically undefined optic nerve hypoplasia syndrome should be screened for albuminuria and, if present, screened for mutations in LAMB2. © Endocrine Society 2019.
Author Keywords
LAMB2; optic nerve hypoplasia syndrome; Pierson syndrome
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Monitoring the itinerary of lysosomal cholesterol in Niemann-Pick Type C1-deficient cells after cyclodextrin treatment” (2020) Journal of Lipid Research
Monitoring the itinerary of lysosomal cholesterol in Niemann-Pick Type C1-deficient cells after cyclodextrin treatment
(2020) Journal of Lipid Research, 61 (3), pp. 403-412.
Feltes, M.a , Gale, S.E.a , Moores, S.a , Ory, D.S.a , Schaffer, J.E.a b
a Department of Medicine, Washington University School of Medicine, St. Louis, MO
b Joslin Diabetes Center, Harvard Medical School, MA, Boston
Abstract
Niemann-Pick disease type C (NPC) disease is a lipid-storage disorder that is caused by mutations in the genes encoding NPC proteins and results in lysosomal cholesterol accumulation. 2-Hydroxypropyl-β-cyclodextrin (CD) has been shown to reduce lysosomal cholesterol levels and enhance sterol homeostatic responses, but CD’s mechanism of action remains unknown. Recent work provides evidence that CD stimulates lysosomal exocytosis, raising the possibility that lysosomal cholesterol is released in exosomes. However, therapeutic concentrations of CD do not alter total cellular cholesterol, and cholesterol homeostatic responses at the ER are most consistent with increased ER membrane cholesterol. To address these disparate findings, here we used stable isotope labeling to track the movement of lipoprotein cholesterol cargo in response to CD in NPC1-deficient U2OS cells. Although released cholesterol was detectable, it was not associated with extracellular vesicles. Rather, we demonstrate that lysosomal cholesterol trafficks to the plasma membrane (PM), where it exchanges with lipoprotein-bound cholesterol in a CD-dependent manner. We found that in the absence of suitable extracellular cholesterol acceptors, cholesterol exchange is abrogated, cholesterol accumulates in the PM, and reesterification at the ER is increased. These results support a model in which CD promotes intracellular redistribution of lysosomal cholesterol, but not cholesterol exocytosis or efflux, during the restoration of cholesterol homeostatic responses. Copyright © 2020 Feltes et al.
Author Keywords
2-hydroxpropyl-β-cyclodextrin; cellular homeostasis; drug therapy; lipoproteins; lysosomal storage disorder; stable isotope tracers; trafficking
Document Type: Article
Publication Stage: Final
Source: Scopus
“Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state” (2020) eLife
Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state
(2020) eLife, 9, art. no. e53901, .
Taylor, K.C.a b , Kang, P.W.c , Hou, P.c , Yang, N.-D.c , Kuenze, G.b d , Smith, J.A.a b , Shi, J.c , Huang, H.a b , White, K.M.c , Peng, D.a b e , George, A.L., Jr.f , Meiler, J.b d g , McFeeters, R.L.h , Cui, J.c , Sanders, C.R.a b i
a Department of Biochemistry, Vanderbilt University, Nashville, TN 37240, United States
b Center for Structural Biology, Vanderbilt University, Nashville, TN 37240, United States
c Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders and Cardiac Bioelectricity, Arrhythmia Center, Washington University, St. Louis, MO 63130, United States
d Departments of Chemistry and Pharmacology, Vanderbilt University, Nashville, TN 37240, United States
e Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States
f Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
g Department of Bioinformatics, Vanderbilt University Medical Center, Nashville, TN 37232, United States
h Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, United States
i Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
Abstract
Voltage-gated ion channels feature voltage sensor domains (VSDs) that exist in three distinct conformations during activation: resting, intermediate, and activated. Experimental determination of the structure of a potassium channel VSD in the intermediate state has previously proven elusive. Here, we report and validate the experimental three-dimensional structure of the human KCNQ1 voltage-gated potassium channel VSD in the intermediate state. We also used mutagenesis and electrophysiology in Xenopus laevis oocytes to functionally map the determinants of S4 helix motion during voltage-dependent transition from the intermediate to the activated state. Finally, the physiological relevance of the intermediate state KCNQ1 conductance is demonstrated using voltage-clamp fluorometry. This work illuminates the structure of the VSD intermediate state and demonstrates that intermediate state conductivity contributes to the unusual versatility of KCNQ1, which can function either as the slow delayed rectifier current (IKs) of the cardiac action potential or as a constitutively active epithelial leak current. © 2020, eLife Sciences Publications Ltd. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Neural mechanisms of economic choices in mice” (2020) eLife
Neural mechanisms of economic choices in mice
(2020) eLife, 9, art. no. e49669, .
Kuwabara, M., Kang, N., Holy, T.E., Padoa-Schioppa, C.
Department of Neuroscience, Washington University in St Louis, St Louis, MO 63110, United States
Abstract
Economic choices entail computing and comparing subjective values. Evidence from primates indicates that this behavior relies on the orbitofrontal cortex. Conversely, previous work in rodents provided conflicting results. Here we present a mouse model of economic choice behavior, and we show that the lateral orbital (LO) area is intimately related to the decision process. In the experiments, mice chose between different juices offered in variable amounts. Choice patterns closely resembled those measured in primates. Optogenetic inactivation of LO dramatically disrupted choices by inducing erratic changes of relative value and by increasing choice variability. Neuronal recordings revealed that different groups of cells encoded the values of individual options, the binary choice outcome and the chosen value. These groups match those previously identified in primates, except that the neuronal representation in mice is spatial (in monkeys it is good-based). Our results lay the foundations for a circuit-level analysis of economic decisions. © 2020, eLife Sciences Publications Ltd. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Ordinary Claims Require Ordinary Evidence: A Lack of Direct Support for Equalitarian Bias in the Social Sciences” (2020) Psychological Inquiry
Ordinary Claims Require Ordinary Evidence: A Lack of Direct Support for Equalitarian Bias in the Social Sciences
(2020) Psychological Inquiry, 31 (1), pp. 42-47.
Lai, C.K.
Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
Document Type: Note
Publication Stage: Final
Source: Scopus
“Perimortem versus postmortem damage: The recent case of Cioclovina 1” (2020) American Journal of Physical Anthropology
Perimortem versus postmortem damage: The recent case of Cioclovina 1
(2020) American Journal of Physical Anthropology, .
Soficaru, A.D.a , Trinkaus, E.b
a Department of Archaeology, University of Southampton, Southampton, United Kingdom
b Department of Anthropology, Washington University, Saint Louis, MO, United States
Abstract
Objectives: Kranioti, Grigorescu, and Harvati have recently described (PLoS One 2019, 14(7),e0216718) the breakage to the Cioclovina 1 earlier Upper Paleolithic cranium as indicating fatal interhuman blunt trauma. We have reassessed their analysis in terms of the specimen’s condition at discovery, its current condition, and the post-discovery history of the cranium. Materials and Methods: The original Cioclovina 1 neurocranium and currently associated pieces were visually assessed for the nature of the damage to them, and the records of its discovery, the original 1942 photographs, and their subsequent history in Bucharest were reviewed. Results: The damage to Cioclovina 1, attributed by Kranioti and colleagues to perimortem blunt trauma, was not present at the time of its 1940–41 discovery in the Peştera Cioclovina Uscată. The “trauma” is from the World War II bombing of the University of Bucharest and subsequent attempts to restore the cranium. The damage does not, and cannot, document interhuman violence in the Pleistocene. Conclusions: Although other cases of antemortem and perimortem trauma are known from the earlier Upper Paleolithic, and Pleistocene humans more broadly, there is absolutely no evidence of perimortem trauma on the Cioclovina 1 cranium. Proper assessment of levels and patterns of human trauma in the Pleistocene must be based on the correct paleontological, taphonomic, and historical assessment of the fossil remains in question. © 2020 Wiley Periodicals, Inc.
Author Keywords
cranium; late Pleistocene; trauma; violence
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Auditory exposure of high-risk infants discharged from the NICU and the impact of social factors” (2020) Acta Paediatrica, International Journal of Paediatrics
Auditory exposure of high-risk infants discharged from the NICU and the impact of social factors
(2020) Acta Paediatrica, International Journal of Paediatrics, .
Liszka, L.a , Heiny, E.a , Smith, J.b , Schlaggar, B.L.c d , Mathur, A.e , Pineda, R.a f g h
a Washington University Program in Occupational Therapy, St. Louis, MO, United States
b Saint Louis Children’s Hospital Department of Quality, Safety and Practice Excellence, St. Louis, MO, United States
c Kennedy Krieger Institute, Baltimore, MD, United States
d Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States
e Division of Neonatal-Perinatal Medicine, SSM Health Cardinal Glennon Children’s Hospital, St. Louis, MO, United States
f Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
g Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, United States
h Department of Pediatrics, Keck School of Medicine, Los Angeles, CA, United States
Abstract
Aim: To (a) define the early home auditory environment of high-risk infants within one month of neonatal intensive care unit (NICU) discharge, (b) compare auditory exposures in the home environment to the NICU environment, and (c) define relationships between maternal/infant factors and auditory exposures within the home. Methods: Seventy-three high-risk infants (48 high-risk infants in the NICU at term-equivalent age and 25 high-risk infants in the home following NICU discharge) had auditory exposures measured. Results: An average of 1.3 hours more noise (P ≤.001) and 2 hours less silence (P =.01) were observed in the NICU compared with the home, but differences varied based on whether comparing to an open ward or private room. Infants with public insurance, lower household income and mothers without a college education were exposed to an average of 2.8, 3.0 and 2.3 hours more TV/electronic sounds respectively (P <.05). An average of 1744 fewer adult words (P =.03) were spoken in households with public insurance. There was an average of 3.1 hours less silence and 4.5 dB louder stimuli among households with lower income (P <.05). Conclusion: Elucidating differences across environments can lead to interventions to foster appropriate auditory exposures to improve language development of high-risk infants. © 2020 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd
Author Keywords
high-risk; insurance; language; preterm; TV
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Multiparametric imaging hippocampal neurodegeneration and functional connectivity with simultaneous PET/MRI in Alzheimer’s disease” (2020) European Journal of Nuclear Medicine and Molecular Imaging
Multiparametric imaging hippocampal neurodegeneration and functional connectivity with simultaneous PET/MRI in Alzheimer’s disease
(2020) European Journal of Nuclear Medicine and Molecular Imaging, .
Yan, S.a b c , Zheng, C.b , Cui, B.d , Qi, Z.a c , Zhao, Z.a c , An, Y.a c , Qiao, L.e , Han, Y.f , Zhou, Y.b , Lu, J.a c d
a Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 Kingshighway Blvd., St. Louis, MO, United States
c Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China
d Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
e Department of Neurology, Yuquan Hospital, Clinical Neuroscience Institute, Medical Center, Tsinghua University, Beijing, China
f Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
Abstract
Purpose: The objective of this study is to investigate the hippocampal neurodegeneration and its associated aberrant functions in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients using simultaneous PET/MRI. Methods: Forty-two cognitively normal controls (NC), 38 MCI, and 22 AD patients were enrolled in this study. All subjects underwent 18F-FDG PET/functional MRI (fMRI) and high-resolution T1-weighted MRI scans on a hybrid GE Signa PET/MRI scanner. Neurodegeneration in hippocampus and its subregions was quantified by regional gray matter volume and 18F-FDG standardized uptake value ratio (SUVR) relative to cerebellum. An iterative reblurred Van Cittert iteration method was used for voxelwise partial volume correction on 18F-FDG PET images. Regional gray matter volume was estimated from voxel-based morphometric analysis with MRI. fMRI data were analyzed after slice time correction and head motion correction using statistical parametric mapping (SPM12) with DPARSF toolbox. The regions of interest including hippocampus, cornu ammonis (CA1), CA2/3/dentate gyrus (DG), and subiculum were defined in the standard MNI space. Results: Patient groups had reduced SUVR, gray matter volume, and functional connectivity compared to NC in CA1, CA2/3/DG, and subiculum (AD < MCI < NC). There was a linear correlation between the left CA2/3DG gray matter volume and 18F-FDG SUVR in AD patients (P < 0.001, r = 0.737). Significant correlation was also found between left CA2/3/DG-superior medial frontal gyrus functional connectivity and left CA2/3/DG hypometabolism in patients with AD. The functional connectivity of right CA1-precuneus in patients with MCI and right subiculum-superior frontal gyrus in patients with AD was positively correlated with mini mental status examination scores (P < 0.05). Conclusion: Our findings demonstrate that the associations existed at subregional hippocampal level between the functional connectivity measured by fMRI and neurodegeneration measured by structural MRI and 18F-FDG PET. Our results may provide a basis for precision neuroimaging of hippocampus in AD. © 2020, The Author(s).
Author Keywords
Alzheimer’s disease; Hippocampal subregions; Hybrid PET/MRI; Neurodegeneration; Voxel-based morphometric analysis
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Neuroactive steroids alphaxalone and CDNC24 are effective hypnotics and potentiators of GABAA currents, but are not neurotoxic to the developing rat brain” (2020) British Journal of Anaesthesia
Neuroactive steroids alphaxalone and CDNC24 are effective hypnotics and potentiators of GABAA currents, but are not neurotoxic to the developing rat brain
(2020) British Journal of Anaesthesia, .
Tesic, V.a , Joksimovic, S.M.a , Quillinan, N.a b , Krishnan, K.c , Covey, D.F.c d , Todorovic, S.M.a b , Jevtovic-Todorovic, V.a
a Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
b Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
c Department of Developmental Biology, Washington University School of Medicine, St LouisMO, United States
d Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St LouisMO, United States
Abstract
Background: The most currently used general anaesthetics are potent potentiators of γ-aminobutyric acid A (GABAA) receptors and are invariably neurotoxic during the early stages of brain development in preclinical animal models. As causality between GABAA potentiation and anaesthetic-induced developmental neurotoxicity has not been established, the question remains whether GABAergic activity is crucial for promoting/enhancing neurotoxicity. Using the neurosteroid analogue, (3α,5α)-3-hydroxy-13,24-cyclo-18,21-dinorchol-22-en-24-ol (CDNC24), which potentiates recombinant GABAA receptors, we examined whether this potentiation is the driving force in inducing neurotoxicity during development. Methods: The neurotoxic potential of CDNC24 was examined vis-à-vis propofol (2,6-diisopropylphenol) and alphaxalone (5α-pregnan-3α-ol-11,20-dione) at the peak of rat synaptogenesis. In addition to the morphological neurotoxicity studies of the subiculum and medial prefrontal cortex (mPFC), we assessed the extra-, pre-, and postsynaptic effects of these agents on GABAergic neurotransmission in acute subicular slices from rat pups. Results: CDNC24, like alphaxalone and propofol, caused dose-dependent hypnosis in vivo, with a higher therapeutic index. CDNC24 and alphaxalone, unlike propofol, did not cause developmental neuroapoptosis in the subiculum and mPFC. Propofol potentiated post- and extrasynaptic GABAA currents as evidenced by increased spontaneous inhibitory postsynaptic current (sIPSC) decay time and prominent tonic currents, respectively. CDNC24 and alphaxalone had a similar postsynaptic effect, but also displayed a strong presynaptic effect as evidenced by decreased frequency of sIPSCs and induced moderate tonic currents. Conclusions: The lack of neurotoxicity of CDNC24 and alphaxalone may be at least partly related to suppression of presynaptic GABA release in the developing brain. © 2020 British Journal of Anaesthesia
Author Keywords
general anaesthetic; prefrontal cortex; presynaptic; subiculum; synaptic transmission; synaptogenesis
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Franz Joseph Gall on hemispheric symmetries” (2020) Journal of the History of the Neurosciences
Franz Joseph Gall on hemispheric symmetries
(2020) Journal of the History of the Neurosciences, .
Eling, P.a , Finger, S.b
a Department of Psychology and Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands
b Department of Psychological and Brain Sciences, and Program in History of Medicine, Washington University, St. Louis, MO, United States
Abstract
Franz Joseph Gall believed that the two cerebral hemispheres are anatomically and functionally similar, so much so that one could substitute for the other following unilateral injuries. He presented this belief during the 1790s in his early public lectures in Vienna, when traveling through Europe between 1805 and 1807, and in the two sets of books he published after settling in France. Gall seemed to derive his ideas about laterality independently of French anatomist Marie François Xavier Bichat (1771–1802), who formulated his “law of symmetry” at about the same time. He would, however, later cite Bichat, whose ideas about mental derangement were different from his own and who also attempted to explain handedness, a subject on which Gall remained silent. The concept of cerebral symmetry would be displaced by mounting clinical evidence for the hemispheres being functionally different, but neither Gall nor Bichat would live to witness the advent of the concept of cerebral dominance. © 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
Author Keywords
cerebral dominance; Christian Heinrich Ernst Bischoff; Franz Joseph Gall; hemispheric differences; laterality; Ludwig Friedrich von Froriep; Marie François Xavier Bichat; organology; Philip Franz von Walther; phrenology
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid” (2020) Annals of Neurology
Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid
(2020) Annals of Neurology, .
Barthélemy, N.R.a , Liu, H.a , Lu, W.a , Kotzbauer, P.T.a b , Bateman, R.J.a b c , Lucey, B.P.a b
a Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, United States
c Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St Louis, MO, United States
Abstract
Tau hyperphosphorylation is an early step in tau-mediated neurodegeneration and is associated with intracellular aggregation of tau as neurofibrillary tangles, neuronal and synaptic loss, and eventual cognitive dysfunction in Alzheimer disease. Sleep loss increases the cerebrospinal fluid concentration of amyloid-β and tau. Using mass spectrometry, we measured tau and phosphorylated tau concentrations in serial samples of cerebrospinal fluid collected from participants who were sleep-deprived, treated with sodium oxybate, or allowed to sleep normally. We found that sleep loss affected phosphorylated tau differently depending on the modified site. These findings suggest a mechanism for sleep loss to increase risk of Alzheimer disease. ANN NEUROL 2020. © 2020 American Neurological Association
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Functional analysis of proposed substrate-binding residues of Hsp104” (2020) PLoS ONE
Functional analysis of proposed substrate-binding residues of Hsp104
(2020) PLoS ONE, 15 (3), art. no. e0230198, .
Howard, M.K., Sohn, B.S., von Borcke, J., Xu, A., Jackrel, M.E.
Department of Chemistry, Washington University, St. Louis, MO, United States
Abstract
Hsp104 is a hexameric AAA+ yeast disaggregase capable of solubilizing disordered aggregates and amyloid. Hsp104 couples ATP hydrolysis to polypeptide translocation through its central channel. Substrate binding by Hsp104 is mediated primarily by two conserved tyrosine residues in nucleotide binding domain (NBD) 1 and NBD2. Recent structural studies have revealed that an additional tyrosine residue (Y650) located in NBD2 appears to contact substrate and may play an important role in Hsp104 function. Here, we functionally analyze the properties of this proposed Hsp104 –substrate interaction. We find that Y650 is not essential for Hsp104 to confer thermotolerance. Supporting these findings, in a potentiated Hsp104 variant background, the Y650A mutation does not abolish potentiation. However, modulation of this site does have subtle effects on the activity of this potentiated Hsp104 variant. We therefore suggest that while Y650 is not essential for Hsp104 function, its modulation may be useful for fine-tuning Hsp104 properties. © 2020 Howard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Cognitive flexibility and persistent post-surgical pain: the FLEXCAPP prospective observational study” (2020) British Journal of Anaesthesia
Cognitive flexibility and persistent post-surgical pain: the FLEXCAPP prospective observational study
(2020) British Journal of Anaesthesia, .
Vila, M.R.a , Todorovic, M.S.a , Tang, C.a , Fisher, M.a , Steinberg, A.a , Field, B.a , Bottros, M.M.a b , Avidan, M.S.a , Haroutounian, S.a b
a Department of Anesthesiology, Washington University School of Medicine in St Louis, St Louis, MO, United States
b Washington University Pain Center, Washington University School of Medicine in St Louis, St Louis, MO, United States
Abstract
Background: Impaired performance on tasks assessing executive function has been linked to chronic pain. We hypothesised that poor performance on tests assessing the ability to adjust thinking in response to changing environmental stimuli (cognitive flexibility) would be associated with persistent post-surgical pain. Methods: We conducted a single-centre prospective observational study in two perioperative cohorts: patients undergoing total knee arthroplasty or noncardiac chest surgical procedures. The co-primary outcome measures compared preoperative performance on the Trail Making Test and the colour–word matching Stroop test between patients who developed persistent post-surgical pain and those who did not. Secondary outcome measures included the associations between these test scores and pain severity at 6 months. Results: Of 300 participants enrolled, 198 provided 6 month follow-up data. There were no significant differences in preoperative Trail Making Test B minus A times (33 vs 34 s; P=0.59) or Stroop interference T-scores (47th vs 48th percentile; P=0.50) between patients with and without persistent post-surgical pain (primary outcome). Of those who reported persistent post-surgical pain, poorer baseline performance on the colour–word matching Stroop test was associated with higher pain scores at 6 months in both knee arthroplasty (r=–0.32; P=0.04) and chest (r=–0.44; P=0.02) surgeries (secondary outcome). Conclusions: Preoperative cognitive flexibility test performance was not predictive of overall persistent post-surgical pain incidence 6 months after surgery. However, poor performance on the colour–word matching Stroop test was independently associated with more severe persistent post-surgical pain in both cohorts. Clinical trial registration: NCT02579538. © 2020 British Journal of Anaesthesia
Author Keywords
arthroplasty; chronic pain; cognition; mastectomy; postoperative pain; thoracotomy
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Syringomyelia in children with closed spinal dysraphism: Long-term outcomes after surgical intervention” (2020) Journal of Neurosurgery: Pediatrics
Syringomyelia in children with closed spinal dysraphism: Long-term outcomes after surgical intervention
(2020) Journal of Neurosurgery: Pediatrics, 25 (3), pp. 319-325.
Bruzek, A.K.a , Starr, J.a , Garton, H.J.L.a , Muraszko, K.M.a , Maher, C.O.a , Strahle, J.M.b
a Department of Neurosurgery, University of Michigan, Ann Arbor, MI, United States
b Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
Abstract
OBJECTIVE The nature of the relationship between spinal cord syrinx and tethered cord is not well known. It is unclear if surgical cord untethering results in resolution or improvement of an associated syrinx. The objective of this study was to report the response of spinal cord syrinx to surgical cord untethering. METHODS The authors retrospectively reviewed all patients with a syrinx and tethered cord who presented to a single institution over an 11-year interval. Patients with open neural tube defects were excluded. Thirty-one patients were identified, 25 of whom had both clinical and imaging follow-up after surgery. Patients were grouped according to etiology of the tethered cord. Clinical outcomes and syrinx characteristics were recorded. RESULTS Of the 25 patients with tethered cord, 68% (n = 17) were male. The average age at presentation was 2.5 years (0–10.1 years) and age at surgery was 3.7 years (range 1 day to 17 years). Etiologies of tethered cord were lipomyelomeningocele (n = 8), thickened/fatty filum (n = 7), intradural lipoma (n = 5), myelocystocele (n = 2), meningocele (n = 2), and diastematomyelia (n = 1). Twenty-three of the patients underwent primary untethering, whereas 2 patients had received untethering previously at another institution. The average syrinx length and width prior to surgery were 4.81 vertebral levels (SD 4.35) and 5.19 mm (SD 2.55 mm), respectively. Conus level ranged from L1 to S3. Patients were followed for an average of 8.4 years (1.35–15.85 years). Overall there was no significant change in syrinx length or width postoperatively; the average syrinx length increased by 0.86 vertebral levels (SD 4.36) and width decreased by 0.72 mm (SD 2.94 mm). Seven of 25 patients had improvement in at least one presenting symptom, including scoliosis, weakness, bowel/bladder dysfunction, and pain. Eight patients had stable presenting symptoms. Six patients were asymptomatic and 5 patients had new or worsening symptoms, which included scoliosis, pain, or sensory changes. CONCLUSIONS Although some syrinxes improved after surgery for tethered cord, radiological improvement was not consistent and did not appear to be associated with change in clinical symptoms. The decision to surgically untether a cord should be focused on the clinical symptoms and not the presence of a syrinx alone. Further studies are needed to confirm this finding. ©AANS 2020
Author Keywords
Congenital; Spinal dysraphism; Spine; Syrinx; Tethered cord
Document Type: Article
Publication Stage: Final
Source: Scopus
“Uncovering the complex genetics of human personality: response from authors on the PGMRA Model” (2019) Molecular Psychiatry
Uncovering the complex genetics of human personality: response from authors on the PGMRA Model
(2019) Molecular Psychiatry, . Cited 3 times.
Zwir, I.a b , Mishra, P.c , Del-Val, C.b , Gu, C.C.d , de Erausquin, G.A.e , Lehtimäki, T.c , Cloninger, C.R.a f
a Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, United States
b University of Granada, Department of Computer Science, Granada, Spain
c Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center – Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
d Washington University, School of Medicine, Division of Biostatistics, St. Louis, MO, United States
e University of Texas Rio-Grande Valley, School of Medicine, Department of Psychiatry and Neurology, and Institute of Neurosciences, Harlingen, TX, United States
f Washington University, School of Arts and Sciences, Department of Psychological and Brain Sciences, and School of Medicine, Department of Genetics, St. Louis, MO, United States
Document Type: Letter
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access