“Levetiracetam Prophylaxis for Children Admitted With Traumatic Brain Injury” (2022) Pediatric Neurology
Levetiracetam Prophylaxis for Children Admitted With Traumatic Brain Injury
(2022) Pediatric Neurology, 126, pp. 114-119.
Surtees, T.-L.a , Kumar, I.b , Garton, H.J.L.c , Rivas-Rodriguez, F.d , Parmar, H.d , McCaffery, H.b , Riebe-Rodgers, J.b , Shellhaas, R.A.b
a Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, United Statesb Departments of Pediatrics, University of Michigan, Ann Arbor, MI, United Statesc Neurosurgery, University of Michigan, Ann Arbor, MI, United Statesd Radiology, University of Michigan, Ann Arbor, MI, United States
AbstractBackground: Prophylactic antiseizure medications (ASMs) for pediatric traumatic brain injury (TBI) are understudied. We evaluated clinical and radiographic features that inform prescription of ASMs for pediatric TBI. We hypothesized that despite a lack of evidence, levetiracetam is the preferred prophylactic ASM but that prophylaxis is inconsistently prescribed. Methods: This retrospective study assessed children admitted with TBI from January 1, 2017, to December 31, 2019. TBI severity was defined using Glasgow Coma Scale (GCS) scores. Two independent neuroradiologists reviewed initial head computed tomography and brain magnetic resonance imaging. Fisher exact tests and descriptive and regression analyses were conducted. Results: Among 167 children with TBI, 44 (26%) received ASM prophylaxis. All 44 (100%) received levetiracetam. Prophylaxis was more commonly prescribed for younger children, those with neurosurgical intervention, and abnormal neuroimaging (particularly intraparenchymal hematoma) (odds ratio = 10.3, confidence interval 1.8 to 58.9), or GCS ≤12. Six children (13.6%), all on ASM, developed early posttraumatic seizures (EPTSs). Of children with GCS ≤12, four of 17 (23.5%) on levetiracetam prophylaxis developed EPTSs, higher than the reported rate for phenytoin. Conclusions: Although some studies suggest it may be inferior to phenytoin, levetiracetam was exclusively used for EPTS prophylaxis. Intraparenchymal hematoma >1 cm was the single neuroimaging feature associated with ASM prophylaxis regardless of the GCS score. Yet these trends are not equivalent to optimal evidence-based management. We still observed important variability in neuroimaging characteristics and TBI severity for children on prophylaxis. Thus, further study of ASM prophylaxis and prevention of pediatric EPTSs is warranted. © 2021 Elsevier Inc.
Author KeywordsEarly posttraumatic seizure; Pediatric; Seizure prophylaxis; Traumatic brain injury
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids” (2021) Cell Stem Cell
Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids(2021) Cell Stem Cell, 28 (12), pp. 2153-2166.e6.
Popova, G.a b c , Soliman, S.S.a b c , Kim, C.N.a b c , Keefe, M.G.a b c , Hennick, K.M.a b c , Jain, S.d , Li, T.c e , Tejera, D.c e , Shin, D.a b c , Chhun, B.B.f , McGinnis, C.S.g , Speir, M.h , Gartner, Z.J.f g i j , Mehta, S.B.f , Haeussler, M.h , Hengen, K.B.k , Ransohoff, R.R.l , Piao, X.c d e m , Nowakowski, T.J.a b c e f
a Department of Anatomy, University of California, San Francisco, San Francisco, CA, United Statesb Department of Psychiatry, University of California, San Francisco, San Francisco, CA, United Statesc Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, United Statesd Division of Neonatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United Statese Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United Statesf Chan Zuckerberg Biohub, San Francisco, CA, United Statesg Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, United Statesh Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, United Statesi Center for Cellular Construction, University of California, San Francisco, San Francisco, CA, United Statesj Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, United Statesk Department of Biology, Washington University in St. Louis, St. Louis, MO, United Statesl Department of Cell Biology, Harvard Medical School, Boston, MA, United Statesm Newborn Brain Research Institute, University of California, San Francisco, San Francisco, CA, United States
AbstractMicroglia are resident macrophages in the brain that emerge in early development and respond to the local environment by altering their molecular and phenotypic states. Fundamental questions about microglia diversity and function during development remain unanswered because we lack experimental strategies to interrogate their interactions with other cell types and responses to perturbations ex vivo. We compared human microglia states across culture models, including cultured primary and pluripotent stem cell-derived microglia. We developed a “report card” of gene expression signatures across these distinct models to facilitate characterization of their responses across experimental models, perturbations, and disease conditions. Xenotransplantation of human microglia into cerebral organoids allowed us to characterize key transcriptional programs of developing microglia in vitro and reveal that microglia induce transcriptional changes in neural stem cells and decrease interferon signaling response genes. Microglia additionally accelerate the emergence of synchronized oscillatory network activity in brain organoids by modulating synaptic density. © 2021 Elsevier Inc.
Author Keywordsdouble-stranded DNA breaks; human microglia; induced microglia; interferon response; iPSC; microglia; microglia culture; neuro-immune; organoid activity; organoids
Funding detailsF32 1F32MH118785National Institutes of HealthNIHP01 NS083513, R01 NS108446, R01 NS118442Simons FoundationSFSFARI 491371
Document Type: ArticlePublication Stage: FinalSource: Scopus
“A MYT1L syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation” (2021) Neuron
A MYT1L syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation(2021) Neuron, 109 (23), pp. 3775-3792.e14.
Chen, J.a b , Lambo, M.E.c , Ge, X.d , Dearborn, J.T.e , Liu, Y.a b , McCullough, K.B.a b , Swift, R.G.a b , Tabachnick, D.R.a b , Tian, L.c , Noguchi, K.b f , Garbow, J.R.d f g , Constantino, J.N.b f , Gabel, H.W.h , Hengen, K.B.c , Maloney, S.E.b f , Dougherty, J.D.a b f
a Department of Genetics, Washington University School of Medicine, St. Louis, MO, United Statesb Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United Statesc Department of Biology, Washington University School of Medicine, St. Louis, MO, United Statesd Department of Radiology, Washington University School of Medicine, St. Louis, MO, United Statese Department of Medicine, Washington University School of Medicine, St. Louis, MO, United Statesf Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, United Statesg Alvin J Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United Statesh Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
AbstractHuman genetics have defined a new neurodevelopmental syndrome caused by loss-of-function mutations in MYT1L, a transcription factor known for enabling fibroblast-to-neuron conversions. However, how MYT1L mutation causes intellectual disability, autism, ADHD, obesity, and brain anomalies is unknown. Here, we developed a Myt1l haploinsufficient mouse model that develops obesity, white-matter thinning, and microcephaly, mimicking common clinical phenotypes. During brain development we discovered disrupted gene expression, mediated in part by loss of Myt1l gene-target activation, and identified precocious neuronal differentiation as the mechanism for microcephaly. In contrast, in adults we discovered that mutation results in failure of transcriptional and chromatin maturation, echoed in disruptions in baseline physiological properties of neurons. Myt1l haploinsufficiency also results in behavioral anomalies, including hyperactivity, muscle weakness, and social alterations, with more severe phenotypes in males. Overall, our findings provide insight into the mechanistic underpinnings of this disorder and enable future preclinical studies. © 2021 Elsevier Inc.
Author KeywordsADHD; ASD; Autism; Chromatin Accessibility; Hyperactivity; ID; Neuronal Differentiation; Social Motivation; Transcription
Funding detailsNational Institutes of HealthNIH5UL1TR002345, R01MH107515, R01MH124808Brain and Behavior Research FoundationBBRFWashington University in St. LouisWUSTLInstitute of Clinical and Translational SciencesICTSP50 HD103525Washington University School of Medicine in St. LouisWUSMPenn State Clinical and Translational Science InstituteCTSI
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Identification of disease-linked hyperactivating mutations in UBE3A through large-scale functional variant analysis” (2021) Nature Communications
Identification of disease-linked hyperactivating mutations in UBE3A through large-scale functional variant analysis(2021) Nature Communications, 12 (1), art. no. 6809, .
Weston, K.P.a , Gao, X.a , Zhao, J.a , Kim, K.-S.a , Maloney, S.E.b , Gotoff, J.c , Parikh, S.d , Leu, Y.-C.e , Wu, K.-P.e , Shinawi, M.f , Steimel, J.P.g , Harrison, J.S.h , Yi, J.J.a
a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United Statesb Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United Statesc Department of Pediatrics, Geisinger Medical Center, Danville, PA 17822, United Statesd Department of Neurogenetics, Neurosciences Institute, Cleveland Clinic, Cleveland, OH 44106, United Statese Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwanf Division of Genetics and Genomic Medicine, Department of Pediatrics, St. Louis Children’s Hospital, Washington University School of Medicine, St. Louis, MO 63110, United Statesg Deparment of Mechanical Engineering, University of the Pacific, Stockton, CA 95211, United Statesh Department of Chemistry, University of the Pacific, Stockton, CA 95211, United States
AbstractThe mechanisms that underlie the extensive phenotypic diversity in genetic disorders are poorly understood. Here, we develop a large-scale assay to characterize the functional valence (gain or loss-of-function) of missense variants identified in UBE3A, the gene whose loss-of-function causes the neurodevelopmental disorder Angelman syndrome. We identify numerous gain-of-function variants including a hyperactivating Q588E mutation that strikingly increases UBE3A activity above wild-type UBE3A levels. Mice carrying the Q588E mutation exhibit aberrant early-life motor and communication deficits, and individuals possessing hyperactivating UBE3A variants exhibit affected phenotypes that are distinguishable from Angelman syndrome. Additional structure-function analysis reveals that Q588 forms a regulatory site in UBE3A that is conserved among HECT domain ubiquitin ligases and perturbed in various neurodevelopmental disorders. Together, our study indicates that excessive UBE3A activity increases the risk for neurodevelopmental pathology and suggests that functional variant analysis can help delineate mechanistic subtypes in monogenic disorders. © 2021, The Author(s).
Funding detailsNational Institute of Mental HealthNIMHR01MH122786Brain and Behavior Research FoundationBBRFAlfred P. Sloan FoundationSimons FoundationSF387972Whitehall FoundationAngelman Syndrome FoundationASFNational Alliance for Research on Schizophrenia and DepressionNARSAD
Document Type: ArticlePublication Stage: FinalSource: Scopus
“SARS-CoV-2: A potential trigger of dermato-neuro syndrome in a patient with scleromyxedema” (2021) JAAD Case Reports
SARS-CoV-2: A potential trigger of dermato-neuro syndrome in a patient with scleromyxedema(2021) JAAD Case Reports, 18, pp. 99-102.
Fritz, M.a , Tinker, D.b , Wessel, A.W.c , Morris, G.M.b , Goldenberg, L.d , Fesler, M.d , Rukmangadachar, L.e , Hurley, M.Y.b
a University of Kentucky College of Medicine, Lexington, KY, United Statesb Department of Dermatology, Saint Louis University, St. Louis, MO, United Statesc Washington University School of Medicine, St. Louis, MO, United Statesd Division of Hematology, Oncology, & Cellular Therapy, Department of Internal Medicine, Saint Louis University, St. Louis, MO, United Statese Department of Neurology, Saint Louis University, St. Louis, MO, United States
Author KeywordsCOVID-19; dermato-neuro syndrome; epilepsy; IVIG; mucinoses; SARS-CoV-2; scleromyxedema
Document Type: ArticlePublication Stage: FinalSource: Scopus
“A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function” (2021) Science Advances
A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function(2021) Science Advances, 7 (48), art. no. eabf6935, .
Xiao, M.-F.a , Roh, S.-E.a , Zhou, J.a , Chien, C.-C.a , Lucey, B.P.b , Craig, M.T.c , Hayes, L.N.a , Coughlin, J.M.d , Markus Leweke, F.e f , Jia, M.a , Xu, D.a , Zhou, W.g , Conover Talbot, C.h , Arnold, D.B.i , Staley, M.d , Jiang, C.d , Reti, I.M.d , Sawa, A.a d j k , Pelkey, K.A.l , McBain, C.J.l , Savonenko, A.m , Worley, P.F.a n
a Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United Statesb Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United Statesc Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdomd Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United Statese Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germanyf Youth Mental Health Team, Brain and Mind Centre, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australiag Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United Statesh Transcriptomics and Deep Sequencing Core Facility, Johns Hopkins University School of Medicine, Baltimore, MD, United Statesi Department of Biology, Section of Molecular and Computational Biology, University of Southern California, Los Angeles, CA, United Statesj Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, Baltimore, MD, United Statesk Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United Statesl Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, Bethesda, MD, United Statesm Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, United Statesn Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
AbstractSchizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition. NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses and is coupled to circadian behavior. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. Modeling NPTX2 loss of function results in failure of parvalbumin interneurons in their adaptive contribution to behavioral stress, and animals exhibit multiple neuropsychiatric domains. Because the genetics of schizophrenia encompasses diverse proteins that contribute to excitatory synapse plasticity, the identified vulnerability of NPTX2 function can provide a framework for assessing the impact of genetics and the intersection with stress. © 2021 American Association for the Advancement of Science. All rights reserved.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Brief Electrical Stimulation Accelerates Axon Regeneration and Promotes Recovery Following Nerve Transection and Repair in Mice” (2021) The Journal of Bone and Joint Surgery. American Volume
Brief Electrical Stimulation Accelerates Axon Regeneration and Promotes Recovery Following Nerve Transection and Repair in Mice(2021) The Journal of Bone and Joint Surgery. American Volume, 103 (20), p. e80.
Sayanagi, J., Acevedo-Cintrón, J.A., Pan, D., Schellhardt, L., Hunter, D.A., Snyder-Warwick, A.K., Mackinnon, S.E., Wood, M.D.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
AbstractBACKGROUND: Clinical outcomes following nerve injury repair can be inadequate. Pulsed-current electrical stimulation (ES) is a therapeutic method that facilitates functional recovery by accelerating axon regeneration. However, current clinical ES protocols involve the application of ES for 60 minutes during surgery, which can increase operative complexity and time. Shorter ES protocols could be a strategy to facilitate broader clinical adoption. The purpose of the present study was to determine if a 10-minute ES protocol could improve outcomes. METHODS: C57BL/6J mice were randomized to 3 groups: no ES, 10 minutes of ES, and 60 minutes of ES. In all groups, the sciatic nerve was transected and repaired, and, in the latter 2 groups, ES was applied after repair. Postoperatively, changes to gene expression from dorsal root ganglia were measured after 24 hours. The number of motoneurons regenerating axons was determined by retrograde labeling at 7 days. Histomorphological analyses of the nerve were performed at 14 days. Function was evaluated serially with use of behavioral tests up to 56 days postoperatively, and relative muscle weight was evaluated. RESULTS: Compared with the no-ES group, both ES groups demonstrated increased regeneration-associated gene expression within dorsal root ganglia. The 10-minute and 60-minute ES groups demonstrated accelerated axon regeneration compared with the no-ES group based on increased numbers of labeled motoneurons regenerating axons (mean difference, 202.0 [95% confidence interval (CI), 17.5 to 386.5] and 219.4 [95% CI, 34.9 to 403.9], respectively) and myelinated axon counts (mean difference, 559.3 [95% CI, 241.1 to 877.5] and 339.4 [95% CI, 21.2 to 657.6], respectively). The 10-minute and 60-minute ES groups had improved behavioral recovery, including on grid-walking analysis, compared with the no-ES group (mean difference, 11.9% [95% CI, 3.8% to 20.0%] and 10.9% [95% CI, 2.9% to 19.0%], respectively). There was no difference between the ES groups in measured outcomes. CONCLUSIONS: A 10-minute ES protocol accelerated axon regeneration and facilitated functional recovery. CLINICAL RELEVANCE: The brief (10-minute) ES protocol provided similar benefits to the 60-minute protocol in an acute sciatic nerve transection/repair mice model and merits further studies. Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Neurotoxins subvert the allosteric activation mechanism of SARM1 to induce neuronal loss” (2021) Cell Reports
Neurotoxins subvert the allosteric activation mechanism of SARM1 to induce neuronal loss(2021) Cell Reports, 37 (3), art. no. 109872, .
Wu, T.a d , Zhu, J.a c , Strickland, A.a , Ko, K.W.b , Sasaki, Y.a , Dingwall, C.B.a , Yamada, Y.a , Figley, M.D.b , Mao, X.a , Neiner, A.a , Bloom, A.J.a c , DiAntonio, A.b c , Milbrandt, J.a c
a Department of Genetics, Washington University Medical School, St. Louis, MO 63110, United Statesb Department of Developmental Biology, Washington University Medical School, St. Louis, MO 63110, United Statesc Needleman Center for Neurometabolism and Axonal Therapeutics, Washington University School of Medicine in Saint Louis, St. Louis, MO 63114, United Statesd Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
AbstractSARM1 is an inducible TIR-domain NAD+ hydrolase that mediates pathological axon degeneration. SARM1 is activated by an increased ratio of NMN to NAD+, which competes for binding to an allosteric activating site. When NMN binds, the TIR domain is released from autoinhibition, activating its NAD+ hydrolase activity. The discovery of this allosteric activating site led us to hypothesize that other NAD+-related metabolites might activate SARM1. Here, we show the nicotinamide analog 3-acetylpyridine (3-AP), first identified as a neurotoxin in the 1940s, is converted to 3-APMN, which activates SARM1 and induces SARM1-dependent NAD+ depletion, axon degeneration, and neuronal death. In mice, systemic treatment with 3-AP causes rapid SARM1-dependent death, while local application to the peripheral nerve induces SARM1-dependent axon degeneration. We identify 2-aminopyridine as another SARM1-dependent neurotoxin. These findings identify SARM1 as a candidate mediator of environmental neurotoxicity and suggest that SARM1 agonists could be developed into selective agents for neurolytic therapy. © 2021 The Author(s)
Author Keywordsbase exchange reaction; mass spectrometry; metabolism; myelin; NAMPT; neurolytic block; NMNAT; sciatic nerve; tibial nerve; Vacor
Funding detailsNational Institutes of HealthNIHR01CA219866, R01NS087632, RF1AG013730
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Whole egg consumption and cognitive function among US older adults” (2021) Journal of Human Nutrition and Dietetics
Whole egg consumption and cognitive function among US older adults(2021) Journal of Human Nutrition and Dietetics, .
An, R.a , Li, D.a , McCaffrey, J.b , Khan, N.c
a Department of Brown School, Washington University, St. Louis, MO, United Statesb Office of Extension and Outreach, University of Illinois, Champaign, IL, United Statesc Department of Kinesiology and Community Health, University of Illinois, Champaign, IL, United States
AbstractBackground: Eggs are an affordable food providing many shortfall nutrients with the potential to improve cognitive health. We assessed the relationship between whole egg consumption and cognitive functioning among a US nationally representative sample of older adults. Methods: Individual-level data (2816 adults, aged ≥ 60 years) were obtained from the National Health and Nutrition Examination Survey (NHANES) 2011–2012 and 2013–2014 waves. Cognitive assessments included the Consortium to Establish a Registry for Alzheimer’s Disease Word List Learning Test (CERAD-WL), Word List Recall Test (CERAD-DR), Animal Fluency Test (AF) and Digit Symbol Substitution Test (DSST). A composite cognitive z-score was constructed based on the individual tests to represent one’s overall cognitive functioning. Multiple linear and logistic regressions were performed to examine the effect of whole egg consumption on cognitive functioning, adjusting for individual characteristics and survey design. Results: Approximately 57% of older adults consumed whole eggs, with an average daily intake of 34 g of whole egg equivalent among consumers. The average z-scores of the CERAD-WL, CERAD-DR, AF and DSST tests were −0.08, 0.23, 0.37 and 0.42, respectively, and the overall composite cognitive z-score was 0.24 among older adults. Regression analyses found that neither whole egg consumption status, nor daily intake quantity was associated with cognitive test scores. Conclusions: No association was found between whole egg consumption and cognitive functioning among US older adults. Study limitations included cross-sectional study design and measurement errors. Future studies with longitudinal or experimental design are warranted to examine the possible link between egg consumption and cognition in older adults. © 2021 The British Dietetic Association Ltd.
Author Keywordsattitudes and behaviour; cellular and physiological function; cognition; dietary advice; dietary influences; elderly; food choice; food intake; health eating
Funding detailsEgg Nutrition CenterENC
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Associations between education and dementia in the caribbean and the United States: An international comparison” (2021) Alzheimer’s and Dementia: Translational Research and Clinical Interventions
Associations between education and dementia in the caribbean and the United States: An international comparison(2021) Alzheimer’s and Dementia: Translational Research and Clinical Interventions, 7 (1), art. no. e12204, .
Li, J.a , Llibre-Guerra, J.J.b , Harrati, A.c , Weiss, J.d , Jiménez-Velázquez, I.Z.e , Acosta, D.f , Llibre-Rodriguez, J.J.g , Liu, M.-M.d , Dow, W.H.d h
a Department of Population Health Sciences, Weill Cornell Medical College, Cornell University, 402 E 67th St, New York, NY 10065, United Statesb Department of Neurology, Washington University in St. Louis, St. Louis, MO, United Statesc Department of Primary Care and Population Health, School of Medicine, Stanford University, Stanford, CA, United Statesd Department of Demography, University of California at Berkeley, Berkeley, CA, United Statese Department of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico, United Statesf Universidad Nacional Pedro Henriquez Ureña (UNPHU), Santo Domingo, Dominican Republicg Medical University of Havana, Havana, Cubah School of Public Health, University of California at Berkeley, Berkeley, CA, United States
AbstractIntroduction: Despite high dementia prevalence in Hispanic populations globally, especially Caribbean Hispanics, no study has comparatively examined the association between education and dementia among Hispanics living in the Caribbean Islands and older adults in the United States. Methods: We used data on 6107 respondents aged 65 and older in the baseline wave of the population-based and harmonized 10/66 survey from Cuba, the Dominican Republic, and Puerto Rico, collected between 2003 and 2008, and 11,032 respondents aged 65 and older from the U.S.-based Health and Retirement Study data in 2014, a total of 17,139 individuals. We estimated multivariable logistic regression models examining the association between education and dementia, adjusted for age, income, assets, and occupation. The models were estimated separately for the Caribbean population (pooled and by setting) and the U.S. population by race/ethnicity (Hispanic, Black, and White), followed by pooled models across all populations Results: In the Caribbean population, the relative risk of dementia among low versus high educated adults was 1.45 for women (95% confidence interval [CI] 1.17, 1.74) and 1.92 (95% CI 1.35, 2.49) for men, smaller compared to those in the United States, especially among non-Hispanic Whites (women: 2.78, 95% CI 1.94, 3.61; men: 5.98, 95% CI 4.02, 7.95). Discussion: The differential associations between education and dementia across the Caribbean and US settings may be explained by greater disparities in social conditions in the United States compared to the Caribbean, such as access to health care, healthy behaviors, and social stressors, which serve as potentially important mediators. © 2021 The Authors.
Author KeywordsCaribbean; Dementia; Education; Hispanics; International comparison; Older adults
Funding detailsNational Institutes of HealthNIHK01AG066946, P30AG012839, R01AG064778Robert Wood Johnson FoundationRWJFUniversity of PennsylvaniaJohns Hopkins UniversityJHUT32AG000246
Document Type: ArticlePublication Stage: FinalSource: Scopus
“The reward positivity shows increased amplitude and decreased latency with increasing age in early childhood” (2021) Developmental Science
The reward positivity shows increased amplitude and decreased latency with increasing age in early childhood(2021) Developmental Science, .
Hennefield, L.a , Gilbert, K.a , Whalen, D.a , Giorio, C.a , Camacho, L.E.Q.a , Kelly, D.a , Fleuchaus, E.a , Barch, D.M.a b , Luby, J.L.a , Hajcak, G.c
a Washington University School of Medicine, St. Louis, MO, United Statesb Washington University, St. Louis, MO, United Statesc Florida State University, Tallahassee, FL, United States
AbstractThe reward positivity (RewP) is a widely studied measure of neural response to rewards, yet little is known about normative developmental characteristics of the RewP during early childhood. The present study utilized a pooled community sample of 309 4- to 6-year-old children who participated in the Doors guessing game to examine the latency and amplitude of the RewP. Peak detection of the gain-loss difference waveform was conducted for electrodes Fz, Cz, Pz, Oz and the mean activity in a 100 ms window centered around this peak was analyzed. There was a significant decrease in RewP latency (RewP was earlier) and increase in RewP amplitude (RewP magnitude was larger) with advancing age in this cross-sectional analysis. Further, these were independent effects, as both RewP latency and RewP amplitude were uniquely associated with children’s age. Moreover, our results indicate that the RewP latency in 4- to 6-year-olds falls outside the 250–350 ms window typically used to quantify the RewP (RewP latency in our sample = 381 ms; SD = 60.15). The internal consistency for latency (.64) and amplitude (.27) of the RewP were characterized by moderate to low reliability, consistent with previous work on the reliability of difference scores. Overall, results demonstrate RewP differences in both timing and amplitude across age in early childhood, and suggest that both amplitude and latency of the RewP might function as individual difference measures of reward processing. These findings are discussed in the context of methodological considerations and the development of reward processing across early childhood. © 2021 John Wiley & Sons Ltd.
Author Keywordschildhood; development; ERP; reward positivity; reward processing; RewP
Funding detailsNational Institute of Mental HealthNIMHK23 MH115074, K23 MH118426, L30 MH108015, R01 MH098454, T32 MH100019Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHDF32 HD093273, R21 HD095490
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Scalable and modular wireless-network infrastructure for large-scale behavioural neuroscience” (2021) Nature Biomedical Engineering
Scalable and modular wireless-network infrastructure for large-scale behavioural neuroscience(2021) Nature Biomedical Engineering, .
Qazi, R.a b , Parker, K.E.c d e f , Kim, C.Y.a , Rill, R.g , Norris, M.R.c d e f h , Chung, J.g , Bilbily, J.c d e f i , Kim, J.R.c d e f , Walicki, M.C.c d e f , Gereau, G.B.c d e f , Lim, H.g , Xiong, Y.j , Lee, J.R.k , Tapia, M.A.l , Kravitz, A.V.i , Will, M.J.l , Ha, S.g , McCall, J.G.c d e f h , Jeong, J.-W.a
a School of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Koreab Department of Electrical, Computer and Energy Engineering, University of Colorado, Boulder, CO, United Statesc Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United Statesd Department of Pharmaceutical and Administrative Sciences, University of Health Sciences and Pharmacy in St. Louis, St. Louis, MO, United Statese Center for Clinical Pharmacology, University of Health Sciences and Pharmacy in St. Louis and Washington University School of Medicine, St. Louis, MO, United Statesf Washington University Pain Center, Washington University in St. Louis, St. Louis, MO, United Statesg Department of Computer Science, University of Colorado Boulder, Boulder, CO, United Statesh Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United Statesi Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United Statesj Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United Statesk Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO, United Statesl Department of Psychological Sciences, University of Missouri, Columbia, MO, United States
AbstractThe use of rodents to acquire understanding of the function of neural circuits and of the physiological, genetic and developmental underpinnings of behaviour has been constrained by limitations in the scalability, automation and high-throughput operation of implanted wireless neural devices. Here we report scalable and modular hardware and software infrastructure for setting up and operating remotely programmable miniaturized wireless networks leveraging Bluetooth Low Energy for the study of the long-term behaviour of large groups of rodents. The integrated system allows for automated, scheduled and real-time experimentation via the simultaneous and independent use of multiple neural devices and equipment within and across laboratories. By measuring the locomotion, feeding, arousal and social behaviours of groups of mice or rats, we show that the system allows for bidirectional data transfer from readily available hardware, and that it can be used with programmable pharmacological or optogenetic stimulation. Scalable and modular wireless-network infrastructure should facilitate the remote operation of fully automated large-scale and long-term closed-loop experiments for the study of neural circuits and animal behaviour. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Funding detailsNational Institutes of HealthNIHR01NS117899, R25 MH112473Oak Ridge Associated UniversitiesORAUMinistry of Science, ICT and Future PlanningMSIPNRF-2020M3A9G8018572, NRF-2021R1A2C4001483National Research Foundation of KoreaNRF
Document Type: ArticlePublication Stage: Article in PressSource: Scopus