“A Casz1–NuRD complex regulates temporal identity transitions in neural progenitors” (2021) Scientific Reports
A Casz1–NuRD complex regulates temporal identity transitions in neural progenitors
(2021) Scientific Reports, 11 (1), art. no. 3858, .
Mattar, P.a f g , Jolicoeur, C.a , Dang, T.f g , Shah, S.f g , Clark, B.S.b c , Cayouette, M.a d e
a Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada
b John F. Hardesty, MD, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Anatomy and Cell Biology, and Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada
e Department of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada
f Department of Cell and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
g Ottawa Health Research Institute (OHRI), Ottawa, ON K1H 8L6, Canada
Abstract
Neural progenitor cells undergo identity transitions during development to ensure the generation different types of neurons and glia in the correct sequence and proportions. A number of temporal identity factors that control these transitions in progenitor competence have been identified, but the molecular mechanisms underlying their function remain unclear. Here, we asked how Casz1, the mammalian orthologue of Drosophila castor, regulates competence during retinal development. We show that Casz1 is required to control the transition between neurogenesis and gliogenesis. Using BioID proteomics, we reveal that Casz1 interacts with the nucleosome remodeling and deacetylase (NuRD) complex in retinal cells. Finally, we show that both the NuRD and the polycomb repressor complexes are required for Casz1 to promote the rod fate and suppress gliogenesis. As additional temporal identity factors have been found to interact with the NuRD complex in other contexts, we propose that these factors might act through this common biochemical process to regulate neurogenesis. © 2021, The Author(s).
Funding details
Research to Prevent BlindnessRPB
Canadian Institutes of Health ResearchCIHRFDN 159936, PJT 166032
National Institutes of HealthNIHR00EY027844
Document Type: Article
Publication Stage: Final
Source: Scopus
“Ethanol, neurosteroids and cellular stress responses: Impact on central nervous system toxicity, inflammation and autophagy” (2021) Neuroscience and Biobehavioral Reviews
Ethanol, neurosteroids and cellular stress responses: Impact on central nervous system toxicity, inflammation and autophagy
(2021) Neuroscience and Biobehavioral Reviews, 124, pp. 168-178.
Fujii, C., Zorumski, C.F., Izumi, Y.
Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Alcohol intake can impair brain function, in addition to other organs such as the liver and kidney. In the brain ethanol can be detrimental to memory formation, through inducing the integrated stress response/endoplasmic reticulum stress/unfolded protein response and the molecular mechanisms linking stress to other events such as NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammation and autophagy. This literature review aims to provide an overview of our current understanding of the molecular mechanisms involved in ethanol-induced damage with endoplasmic reticulum stress, integrated stress response, NLRP3 inflammation and autophagy, while discussing the impact of neurosteroids and oxysterols, including allopregnanolone, 25-hydroxycholesterol and 24S-hydroxycholesterol, on the central nervous system. © 2021 Elsevier Ltd
Author Keywords
24S-Hydroxycholesterol; 25-Hydroxycholesterol; Acetaldehyde; Alcohol; Allopregnanolone; Apoptosis; Cell death; Cytokine; Fetal alcohol syndrome; Golgi apparatus; Hippocampus; Lipopolysaccharide; Liver X receptor; Long-term potentiation; Memory; Microglia; Neurotoxicity; NLRP3; Oxysterol; Quercetin; Reactive oxygen species; Salubrinal
Document Type: Review
Publication Stage: Final
Source: Scopus
“SARM1 is required in human derived sensory neurons for injury-induced and neurotoxic axon degeneration” (2021) Experimental Neurology
SARM1 is required in human derived sensory neurons for injury-induced and neurotoxic axon degeneration
(2021) Experimental Neurology, 339, art. no. 113636, .
Chen, Y.-H.c d , Sasaki, Y.a , DiAntonio, A.b c , Milbrandt, J.b c
a Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Needleman Center for Neurometabolism and Axonal Therapeutics, Washington University School of Medicine, St. Louis, MO 63110, United States
d Genome Engineering and iPSC Center, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Axonal degeneration contributes to the pathogenesis of many neurodegenerative disorders, motivating efforts to dissect the mechanism of pathological axon loss in order to develop therapies for axonal preservation. SARM1 is a particularly attractive therapeutic target, as it is an inducible NAD+ cleaving enzyme that is required for axon loss in multiple mouse models of traumatic and degenerative neurological disease. However, it is essential to establish whether SARM1 triggers axon degeneration in human neurons before proceeding with the development of SARM1-directed therapeutics. Here we combine genome engineering with the production of human stem cell-derived neurons to test the role of human SARM1 in traumatic and neurotoxic axon degeneration. We have generated two independent SARM1 knockout human iPSC lines that do not express SARM1 protein upon differentiation into neurons. We have developed a modified sensory neuron differentiation protocol that generates human sensory neurons with high yield and purity. We find that SARM1 is required for axon degeneration in response to both physical trauma and in a cellular model of chemotherapy-induced peripheral neuropathy. Finally, we identify cADPR as a biomarker of SARM1 enzyme activity in both healthy and injured human sensory neurons. These findings are consistent with prior molecular and cellular studies in mouse neurons, and highlight the therapeutic potential of SARM1 inhibition for the prevention and treatment of human neurological disease. © 2021 Elsevier Inc.
Author Keywords
Axon degeneration; NADase; Neurodegeneration; Sarmoptosis; TIR domain
Funding details
National Institutes of HealthNIHR01CA219866, RF1AG013730, RO1NS087632
National Cancer InstituteNCIP30 CA091842
Document Type: Article
Publication Stage: Final
Source: Scopus
“Think big, start small: How nanomedicine could alleviate the burden of rare cns diseases” (2021) Pharmaceuticals
Think big, start small: How nanomedicine could alleviate the burden of rare cns diseases
(2021) Pharmaceuticals, 14 (2), art. no. 109, pp. 1-21.
Faouzi, A.a , Roullin, V.G.b
a Center for Clinical Pharmacology, St. Louis College of Pharmacy, Washington University School of Medicine, St. Louis, MO 63131, United States
b Laboratoire de Nanotechnologies Pharmaceutiques, Faculté de Pharmacie, Université de Montréal, Montréal, QC H3T 1J4, Canada
Abstract
The complexity and organization of the central nervous system (CNS) is widely modu-lated by the presence of the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB), which both act as biochemical, dynamic obstacles impeding any type of undesirable ex-ogenous exchanges. The disruption of these barriers is usually associated with the development of neuropathologies which can be the consequence of genetic disorders, local antigenic invasions, or autoimmune diseases. These disorders can take the shape of rare CNS-related diseases (other than Alzheimer’s and Parkinson’s) which a exhibit relatively low or moderate prevalence and could be part of a potential line of treatments from current nanotargeted therapies. Indeed, one of the most promising therapeutical alternatives in that field comes from the development of nanotechnologies which can be divided between drug delivery systems and diagnostic tools. Unfortunately, the num-ber of studies dedicated to treating these rare diseases using nanotherapeutics is limited, which is mostly due to a lack of interest from industrial pharmaceutical companies. In the present review, we will provide an overview of some of these rare CNS diseases, discuss the physiopathology of these disorders, shed light on how nanotherapies could be of interest as a credible line of treatment, and finally address the major issues which can hinder the development of efficient therapies in that area. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
CNS disorders; Drug delivery systems; Nanomedicine; Nanotechnologies; Orphan diseases; Rare pathologies
Funding details
191486
Philippe Foundation
Natural Sciences and Engineering Research Council of CanadaNSERCRGPIN/06506-2014
Document Type: Review
Publication Stage: Final
Source: Scopus
“Test-Retest Reliability of Neural Correlates of Response Inhibition and Error Monitoring: An fMRI Study of a Stop-Signal Task” (2021) Frontiers in Neuroscience
Test-Retest Reliability of Neural Correlates of Response Inhibition and Error Monitoring: An fMRI Study of a Stop-Signal Task
(2021) Frontiers in Neuroscience, 15, art. no. 624911, .
Korucuoglu, O.a , Harms, M.P.a , Astafiev, S.V.a , Golosheykin, S.a , Kennedy, J.T.a , Barch, D.M.a b , Anokhin, A.P.a
a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States
Abstract
Response inhibition (RI) and error monitoring (EM) are important processes of adaptive goal-directed behavior, and neural correlates of these processes are being increasingly used as transdiagnostic biomarkers of risk for a range of neuropsychiatric disorders. Potential utility of these purported biomarkers relies on the assumption that individual differences in brain activation are reproducible over time; however, available data on test-retest reliability (TRR) of task-fMRI are very mixed. This study examined TRR of RI and EM-related activations using a stop signal task in young adults (n = 56, including 27 pairs of monozygotic (MZ) twins) in order to identify brain regions with high TRR and familial influences (as indicated by MZ twin correlations) and to examine factors potentially affecting reliability. We identified brain regions with good TRR of activations related to RI (inferior/middle frontal, superior parietal, and precentral gyri) and EM (insula, medial superior frontal and dorsolateral prefrontal cortex). No subcortical regions showed significant TRR. Regions with higher group-level activation showed higher TRR; increasing task duration improved TRR; within-session reliability was weakly related to the long-term TRR; motion negatively affected TRR, but this effect was abolished after the application of ICA-FIX, a data-driven noise removal method. © Copyright © 2021 Korucuoglu, Harms, Astafiev, Golosheykin, Kennedy, Barch and Anokhin.
Author Keywords
error monitoring; familial influences; fMRI; response inhibition; stop-signal task; test-retest reliability
Funding details
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
National Institutes of HealthNIHR01DA018899, R01HD083614, R21DA038834
National Institute on Drug AbuseNIDA
Document Type: Article
Publication Stage: Final
Source: Scopus
“Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis” (2021) Multiple Sclerosis Journal
Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis
(2021) Multiple Sclerosis Journal, .
Harroud, A.a h , Marrie, R.A.b j , Fitzgerald, K.C.c , Salter, A.d , Lu, Y.e , Patel, M.f , Kowalec, K.g i
a Department of Neurology, University of California San Francisco, San Francisco, CA, United States
b Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
c Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
d Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States
e Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
f College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada
g Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
h Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, United States
i College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada
j Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
Abstract
Background: Major depressive disorder (MDD) is common in multiple sclerosis (MS) and its incidence rises before MS diagnosis. However, the causality and direction of this association remain unclear. Objective: The objective is to investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR). Methods: We selected genetic instruments associated with risk of MDD (n = 660,937 cases; 1,453,489 controls) and MS (n = 47,429 cases; 68,374 controls). Using two-sample MR, we examined putative causal effects in either direction, with sensitivity analyses to assess pleiotropy. Also, we adjusted for body mass index (BMI) in multivariable MR. Results: We found no effect of genetic liability to MDD on the odds of MS (OR = 1.07/doubling in odds, 95% CI = 0.90–1.28). Similarly, our findings did not support a causal effect of genetic liability to MS on MDD (OR = 1.00/doubling in odds, 95% CI = 0.99–1.01). Despite heterogeneity, sensitivity analyses indicated that bias from pleiotropy was unlikely. Conversely, genetic predisposition toward higher BMI increased the odds of MS (OR = 1.34/SD increase, 95% CI = 1.09–1.65) and MDD (OR = 1.08, 95% CI = 1.01–1.15). Conclusion: This study does not support a causal association between MDD genetic liability and MS susceptibility, and vice versa. Genetic evidence suggesting commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis. © The Author(s), 2021.
Author Keywords
genetic epidemiology; major depressive disorder; Mendelian randomization; Multiple sclerosis
Funding details
Multiple Sclerosis Society of CanadaMSSOCFAN-1808-32256
National Multiple Sclerosis Society
TA-1805-31136
University of ManitobaUM
National Institutes of HealthNIH
National Institute of Mental HealthNIMHK01, 1K01MH121582-01
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Upper extremity transvenous access for neuroendovascular procedures: An international multicenter case series” (2021) Journal of NeuroInterventional Surgery
Upper extremity transvenous access for neuroendovascular procedures: An international multicenter case series
(2021) Journal of NeuroInterventional Surgery, art. no. 017102, .
Abecassis, I.J.a , Saini, V.a b , Phillips, T.J.c , Osbun, J.W.d , Martínez-Galdámez, M.e , Nada, A.a f , Levitt, M.R.g , Crowley, R.W.h , Sattur, M.G.i , Spiotta, A.M.i , Luther, E.a , Chen, S.H.a , Burks, J.a , Jabbour, P.j , Sweid, A.j , Psychogios, M.N.k , Park, M.S.l , Yavagal, D.R.a b , Peterson, E.C.a , Waqas, M.m , Dossani, R.H.m , Davies, J.M.m , Brehm, A.k , Selkirk, G.D.c , Fox, W.C.n , Abud, D.G.o , Galvan Fernandez, J.p , Schüller Arteaga, M.p , Starke, R.M.a
a Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United States
b Neurology, University of Miami, Miami, FL, United States
c Neurological Intervention and Imaging Service of Western Australia, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
d Neurosurgery, Washington University in Saint Louis School of Medicine, Saint Louis, MO, United States
e Interventional Neuroradiology/Endovascular Neurosurgery, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
f Neurological Surgery, Port Said University, Port Said, Egypt
g Neurological Surgery, University of Washington School of Medicine, Seattle, WA, United States
h Department of Neurosurgery, Rush University Medical Center, Chicago, IL, United States
i Neurosurgery, Medical University of South Carolina, Charleston, SC, United States
j Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, United States
k Department of Neuroradiology, Clinic of Radiology and Nuclear Medicine, Basel, University Hospital Basel, Switzerland
l Neurosurgery, University of Virginia, Charlottesville, VA, United States
m Neurosurgery, University at Buffalo, Buffalo, NY, United States
n Neurosurgery, Mayo Clinic Hospital Jacksonville, Jacksonville, FL, United States
o Interventional Neuroradiology, Medical School of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
p Interventional Neuroradiology and Endovascular Neurosurgery, Hospital Clinico Universitario de Valladolid, Valladolid, Castilla y León, Spain
Abstract
Background: Radial artery access for transarterial procedures has gained recent traction in neurointerventional due to decreased patient morbidity, technical feasibility, and improved patient satisfaction. Upper extremity transvenous access (UETV) has recently emerged as an alternative strategy for the neurointerventionalist, but data are limited. Our objective was to quantify the use of UETV access in neurointerventions and to measure failure and complication rates. Methods: An international multicenter retrospective review of medical records for patients undergoing UETV neurointerventions or diagnostic procedures was performed. We also present our institutional protocol for obtaining UETV and review the existing literature. Results: One hundred and thirteen patients underwent a total of 147 attempted UETV procedures at 13 centers. The most common site of entry was the right basilic vein. There were 21 repeat puncture events into the same vein following the primary diagnostic procedure for secondary interventional procedures without difficulty. There were two minor complications (1.4%) and five failures (ie, conversion to femoral vein access) (3.4%). Conclusions: UETV is safe and technically feasible for diagnostic and neurointerventional procedures. Further studies are needed to determine the benefit over alternative venous access sites and the effect on patient satisfaction. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
Author Keywords
angiography; intervention; technique
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Disrupted Salience and Cingulo-Opercular Network Connectivity During Impaired Rapid Instructed Task Learning in Schizophrenia” (2021) Clinical Psychological Science
Disrupted Salience and Cingulo-Opercular Network Connectivity During Impaired Rapid Instructed Task Learning in Schizophrenia
(2021) Clinical Psychological Science, .
Sheffield, J.M.a , Mohr, H.b , Ruge, H.b , Barch, D.M.c d
a Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, United States
b Department of Psychology, Technische Universität Dresden, Germany
c Department of Psychological & Brain Science, Washington University in St. Louis, United States
d Department of Psychiatry, Washington University in St. Louis, United States
Abstract
Rapid instructed task learning (RITL) is the uniquely human ability to transform task information into goal-directed behavior without relying on trial-and-error learning. RITL is a core cognitive process supported by functional brain networks. In patients with schizophrenia, RITL ability is impaired, but the role of functional network connectivity in these RITL deficits is unknown. We investigated task-based connectivity of eight a priori network pairs in participants with schizophrenia (n = 29) and control participants (n = 31) during the performance of an RITL task. Multivariate pattern analysis was used to determine which network connectivity patterns predicted diagnostic group. Of all network pairs, only the connectivity between the cingulo-opercular network (CON) and salience network (SAN) during learning classified patients and control participants with significant accuracy (80%). CON-SAN connectivity during learning was significantly associated with task performance in participants with schizophrenia. These findings suggest that impaired interactions between identification of salient stimuli and maintenance of task goals contributes to RITL deficits in participants with schizophrenia. © The Author(s) 2021.
Author Keywords
cingulo-opercular network; cognitive deficits; MVPA; rapid instructed task learning; salience network; schizophrenia
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Cognitive performance as a predictor of healthcare transition in sickle cell disease” (2021) British Journal of Haematology
Cognitive performance as a predictor of healthcare transition in sickle cell disease
(2021) British Journal of Haematology, .
Saulsberry-Abate, A.C.a , Partanen, M.b , Porter, J.S.c , Podila, P.S.B.d , Hodges, J.R.a , King, A.A.e , Wang, W.C.a , Schreiber, J.E.f g , Zhao, X.h , Kang, G.h , Jacola, L.M.c , Hankins, J.S.a
a Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN, United States
b Princess Maxima Center for Pediatric Oncology, Heidelberglaan, Netherlands
c Department of Psychology, St. Jude Children’s Research Hospital, Memphis, TN, United States
d Methodist Comprehensive Sickle Cell Center, Methodist University Hospital, Memphis, TN, United States
e Program in Occupational Therapy and Departments of Pediatrics and Medicine, Washington University, St. Louis, MO, United States
f Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
g Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
h Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, United States
Abstract
Neurocognitive deficits in sickle cell disease (SCD) may impair adult care engagement. We investigated the relationship between neurocognitive functioning and socio-environmental factors with healthcare transition outcomes. Adolescents aged 15–18 years who had neurocognitive testing and completed a visit with an adult provider were included. Transition outcomes included transfer interval from paediatric to adult care and retention in adult care at 12 and 24 months. Eighty adolescents (59% male, 64% HbSS/HbSβ0-thalassaemia) were included. Mean age at adult care transfer was 18·0 (±0·3) years and transfer interval was 2·0 (±2·3) months. Higher IQ (P = 0·02; PFDR = 0·05) and higher verbal comprehension (P = 0·008; PFDR = 0·024) were associated with <2 and <6 month transfer intervals respectively. Better performance on measures of attention was associated with higher adult care retention at 12 and 24 months (P = 0·009; PFDR = 0·05 and P = 0·04; PFDR = 0·12 respectively). Transfer intervals <6 months were associated with smaller households (P = 0·02; PFDR = 0·06) and households with fewer children (P = 0·02; PFDR = 0·06). Having a working parent was associated with less retention in adult care at 12 and 24 months (P = 0·01; P = 0·02 respectively). Lower IQ, verbal comprehension, attention difficulties and environmental factors may negatively impact transition outcomes. Neurocognitive function should be considered in transition planning for youth with SCD. © 2021 British Society for Haematology and John Wiley & Sons Ltd
Author Keywords
health literacy; neurocognition; sickle cell disease; silent infarcts; socio-determinants of health; transition to adult care
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Recent advances on extracellular vesicles in central nervous system diseases” (2021) Clinical Interventions in Aging
Recent advances on extracellular vesicles in central nervous system diseases
(2021) Clinical Interventions in Aging, 16, pp. 257-274.
Jin, T.a , Gu, J.a , Li, Z.a , Xu, Z.b , Gui, Y.a
a Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China
b Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Extracellular vesicles (EVs) are particles released by multiple cells, encapsu-lated by lipid bilayers and containing a variety of biological materials, including proteins, nucleic acids, lipids and metabolites. With the advancement of separation and characterization methods, EV subtypes and their complex and diverse functions have been recognized. In the central nervous system (CNS), EVs are involved in various physiolo-gical and pathological processes, such as regulation of neuronal firing, synaptic plasticity, formation and maintenance of myelin sheath, propagation of neuroinflammation, neuro-protection, and spread and removal of toxic protein aggregates. Activity-dependent alteration of constituents enables EVs to reflect the change of cell and tissue states, and the wide distribution of EVs in biological fluids endows them with potential as diagnostic and prognostic biomarkers for CNS diseases, including neurodegenerative disease, cerebrovascular disease, traumatic brain disease, and brain tumor. Favorable biocompatibility, ability of crossing the blood–brain barrier and protecting contents from degradation, give promising therapeutic effects of EVs, either collected from mesenchymal stem cells culture conditioned media, or designed as drug delivery vehicles loaded with specific agents. In this review, we summarized EVs’ basic biological proper-ties, and mainly focused on their applications in CNS diseases. © 2021 Jin et al.
Author Keywords
Blood–brain barrier; CNS; EVs; Exosomes; Neurodegenerative disease; Stroke
Funding details
Natural Science Foundation of Zhejiang ProvinceZJNSFY19H090018
2020KY602
National Natural Science Foundation of ChinaNSFC81401038
Document Type: Review
Publication Stage: Final
Source: Scopus
“A Timely Call to Arms: COVID-19, the Circadian Clock, and Critical Care” (2021) Journal of Biological Rhythms
A Timely Call to Arms: COVID-19, the Circadian Clock, and Critical Care
(2021) Journal of Biological Rhythms, .
Haspel, J.a , Kim, M.b , Zee, P.b , Schwarzmeier, T.c , Montagnese, S.d , Panda, S.e , Albani, A.c f , Merrow, M.c
a Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
c Institute of Medical Psychology, Faculty of Medicine, LMU Munich, Munich, Germany
d Department of Medicine, University of Padova, Padova, Italy
e Salk Institute for Biological Studies, La Jolla, CA, United States
f Department of Medicine IV, LMU Munich, Munich, Germany
Abstract
We currently find ourselves in the midst of a global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly infectious novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss aspects of SARS-CoV-2 biology and pathology and how these might interact with the circadian clock of the host. We further focus on the severe manifestation of the illness, leading to hospitalization in an intensive care unit. The most common severe complications of COVID-19 relate to clock-regulated human physiology. We speculate on how the pandemic might be used to gain insights on the circadian clock but, more importantly, on how knowledge of the circadian clock might be used to mitigate the disease expression and the clinical course of COVID-19. © 2021 The Author(s).
Author Keywords
circadian clock; COVID-19; critical care; nutrition; rhythm; SARS-CoV-2; zeitgeber
Funding details
Volkswagen Foundation
Ludwig-Maximilians-Universität MünchenLMU
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Incongruent electrodiagnostic and sonographic evaluations of a trifid median nerve in carpal tunnel syndrome” (2021) Muscle and Nerve
Incongruent electrodiagnostic and sonographic evaluations of a trifid median nerve in carpal tunnel syndrome
(2021) Muscle and Nerve, .
Colorado, B.S.
Departments of Orthopedic Surgery and Neurology, Washington University School of Medicine, St. Louis, MO, United States
Document Type: Letter
Publication Stage: Article in Press
Source: Scopus
“From Hypnos to Ephialtes: waking up to the consequences of accidental awareness during obstetric general anaesthesia” (2021) Anaesthesia
From Hypnos to Ephialtes: waking up to the consequences of accidental awareness during obstetric general anaesthesia
(2021) Anaesthesia, .
Palanisamy, A.a , Paech, M.J.b
a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b King Edward Memorial Hospital, Perth, Australia
Author Keywords
anaesthesia; awareness; general; obstetric
Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus
“The association between manic symptoms in adolescence and preschool symptoms: The importance of family history” (2021) Bipolar Disorders
The association between manic symptoms in adolescence and preschool symptoms: The importance of family history
(2021) Bipolar Disorders, .
Charatcharungkiat, N., Luby, J., Tillman, R., Vogel, A.
Early Emotional Development Program, William Greenleaf Eliot Division of Child and Adolescent Psychiatry, Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
Abstract
Objectives: First, to investigate whether specific manic symptoms in preschool predict manic symptom severity in adolescence. Second, to investigate the interaction between family history (FH) of bipolar disorder (BP) and preschool manic symptoms in predicting later adolescent manic symptom severity. Methods: This analysis utilized data from the Preschool Depression Study (PDS) which followed 306 preschoolers aged 3–6 years over time since 2003. Only subjects who had data both at baseline (age 3–6 years) and at or after age 12 were included (n = 122). Baseline manic symptom severity scores and diagnoses were assessed by the Preschool Age Psychiatric Assessment (PAPA). Manic symptoms severity at age ≥12 was assessed by the Kiddie Mania Rating Scale (KMRS). FH were ascertained by Family Interview for Genetic Studies (FIGS). Multilevel models of KMRS total score at age ≥12 by preschool mania symptoms with gender, baseline age, baseline ADHD, as well as baseline MDD diagnosis as covariates, and false discovery rate correction were used in statistical analysis. Results: Hypertalkativity, flight of ideas, uninhibited gregariousness, decreased need for sleep (DNFS), and increased motor pressure/ motor activity/ energy in preschool were associated with increased KMRS score at age ≥12. Racing thoughts, inappropriate laughing, and DNFS in early childhood were associated with higher manic symptoms in adolescence in subjects with FH of BP compared to those without FH. Conclusion: The longitudinal clinical importance of displaying manic symptoms (racing thoughts, inappropriate laughing, and DNFS) in early childhood varies by FH. Among the aforementioned symptoms, DNFS was a robust predictor of later manic symptoms. Assessing FH of BP is very important in clinical risk prediction from early childhood. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Author Keywords
adolescence; adolescent; bipolar; childhood; family history; juvenile; mania; manic symptoms; pediatric; preschool
Funding details
National Institute of Mental HealthNIMHR25 MH112473, T32 MH100019, R01 MH090786
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer’s disease modification” (2021) Alzheimer’s and Dementia
Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer’s disease modification
(2021) Alzheimer’s and Dementia, .
Izzo, N.J.a , Yuede, C.M.b , LaBarbera, K.M.a , Limegrover, C.S.a , Rehak, C.a , Yurko, R.a , Waybright, L.a , Look, G.a , Rishton, G.a , Safferstein, H.a , Hamby, M.E.a , Williams, C.a , Sadlek, K.a , Edwards, H.M.b , Davis, C.S.c , Grundman, M.d e , Schneider, L.S.f , DeKosky, S.T.g , Chelsky, D.h , Pike, I.i , Henstridge, C.j , Blennow, K.k l , Zetterberg, H.k l m , LeVine, H., IIIn , Spires-Jones, T.L.o , Cirrito, J.R.b , Catalano, S.M.a
a Cognition Therapeutics Inc., Pittsburgh, PA, United States
b Washington University, St. Louis, MO, United States
c CSD Biostatistics Inc., Oro Valley, AZ, United States
d Global R&D Partners, San Diego, CA, United States
e University of California San Diego, San Diego, CA, United States
f Keck School of Medicine of USC, Los Angeles, CA, United States
g McKnight Brain Institute, University of Florida, Gainesville, FL, United States
h Caprion Biosciences, Montreal, QC, Canada
i Proteome Sciences, London, United Kingdom
j University of Dundee School of Medicine, Dundee, United Kingdom
k University of Gothenburg, Mölndal, Sweden
l Sahlgrenska University Hospital, Mölndal, Sweden
m UCL Institute of Neurology, London, United Kingdom
n Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States
o The University of Edinburgh, Edinburgh, United Kingdom
Abstract
Introduction: Amyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer’s disease (AD) patients’ brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812’s effect on Aβ oligomer pathobiology in preclinical AD models and evaluated CT1812’s impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). Methods: Experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APPSwe/PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer-induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPPSwe/Lnd+ and wild-type littermates. A multicenter, double-blind, placebo-controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini-Mental State Examination 18–26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme-linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo-treated dosing groups. Results: CT1812 significantly and dose-dependently displaced Aβ oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aβ oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD-related proteins dysregulated in CSF. Discussion: These preclinical studies demonstrate the novel disease-modifying mechanism of action of CT1812 against AD and Aβ oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease-related signaling pathways in AD patients, supporting further development of CT1812. © 2021 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association
Author Keywords
Abeta oligomers; Alzheimer’s disease; clinical trial; sigma-2 receptor; synapse
Funding details
National Institute on AgingNIAAG037337, AG051593, AG054176, AG055247
National Institute of Neurological Disorders and StrokeNINDSNS080576, NS083175
Alzheimer’s Drug Discovery FoundationADDF20100501
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Quality of life in isolated dystonia: Non-motor manifestations matter” (2021) Journal of Neurology, Neurosurgery and Psychiatry
Quality of life in isolated dystonia: Non-motor manifestations matter
(2021) Journal of Neurology, Neurosurgery and Psychiatry, art. no. jnnp-2020-325193, .
Junker, J.a b , Berman, B.D.c , Hall, J.d , Wahba, D.W.e , Brandt, V.f , Perlmutter, J.S.g , Jankovic, J.h , Malaty, I.A.i , Wagle Shukla, A.i , Reich, S.G.j , Espay, A.J.k , Duque, K.R.k , Patel, N.l , Roze, E.m n , Vidailhet, M.m n , Jinnah, H.A.o , Brüggemann, N.a b p
a Department of Neurology, University of Luebeck, Luebeck, Germany
b Institute of Neurogenetics, University of Luebeck, Luebeck, Germany
c Department of Neurology, Virginia Commonwealth University, Richmond, VA, United States
d Southampton Education School, University of Southampton, Southampton, United Kingdom
e BayCare Laboratories, BayCare Health Systems, Tampa, FL, United States
f School of Psychology, Centre for Innovation in Mental Health, University of Southampton, Southampton, United Kingdom
g Departments of Neurology, Radiology, Neuroscience, Physical Therapy and Occupational Therapy, Washington University in St. Louis, St. Louis, MO, United States
h Parkinsons’ Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, United States
i Department of Neurology, Fixel Institute for Neurologic Disorders, University of Florida, Gainesville, FL, United States
j Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, United States
k Department of Neurology, University of Cincinnati, Cincinnati, OH, United States
l Department of Neurology, Henry Ford Hospital West Bloomfield, West Bloomfield, MI, United States
m Departement de Neurologie, AP-HP, Hopital de la Pitie-Salpetriere, Paris, France
n Institut du Cerveau-Paris Brain Institute-ICM, Inserm 1127, Cnrs 7225, Sorbonne Universités, Paris, France
o Department of Neurology and Human Genetics, Emory University, Atlanta, GA, United States
p Center of Brain, Behavior and Metabolism, University of Luebeck, Luebeck, Germany
Abstract
Objective: To evaluate the relationship between health-related quality of life (HR-QoL) and both physical and psychiatric factors in a large, international, multicentre cohort of patients with isolated dystonia, the Dystonia Coalition. Methods: Natural history data from 603 patients with isolated dystonia (median age 57 years (IQR: 48 to 64 years), 67.0% women) were prospectively acquired and analysed. HR-QoL (RAND 36-Item Health Survey), severity of depressive symptoms, generalised anxiety (Hospital Anxiety and Depression Scale) and social anxiety (Liebowitz Social Anxiety Scale) were assessed. Dystonia severity (Burke-Fahn-Marsden Dystonia Rating Scale) and dystonic tremor were examined. Statistical predictors of HR-QoL were calculated using saturated path analysis. Results: Reduced HR-QoL was strongly associated with the degree of depressive symptoms and generalised and social anxiety (8/8 RAND 36 subscales, p≤0.001). Increased dystonia severity was associated with worse physical functioning, physical and emotional role functioning and social functioning (all p≤0.001). The presence of tremor correlated with worse physical functioning and pain (all p≤0.006). Younger age was associated with reduced emotional well-being and vitality (all p≤0.006). There were no HR-QoL differences between sexes. Conclusion: HR-QoL in isolated dystonia is strongly associated with psychiatric and physical features. While current standard of care focus on motor aspects of dystonia, comprehensive care should address both physical and mental aspects of health. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Deep learning-based T1-enhanced selection of linear attenuation coefficients (DL-TESLA) for PET/MR attenuation correction in dementia neuroimaging” (2021) Magnetic Resonance in Medicine
Deep learning-based T1-enhanced selection of linear attenuation coefficients (DL-TESLA) for PET/MR attenuation correction in dementia neuroimaging
(2021) Magnetic Resonance in Medicine, .
Chen, Y.a , Ying, C.b , Binkley, M.M.a , Juttukonda, M.R.c d , Flores, S.e , Laforest, R.e , Benzinger, T.L.S.e , An, H.a e b e
a Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
c Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States
d Department of Radiology, Harvard Medical School, Boston, MA, United States
e Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
Abstract
Purpose: The accuracy of existing PET/MR attenuation correction (AC) has been limited by a lack of correlation between MR signal and tissue electron density. Based on our finding that longitudinal relaxation rate, or R1, is associated with CT Hounsfield unit in bone and soft tissues in the brain, we propose a deep learning T1-enhanced selection of linear attenuation coefficients (DL-TESLA) method to incorporate quantitative R1 for PET/MR AC and evaluate its accuracy and longitudinal test–retest repeatability in brain PET/MR imaging. Methods: DL-TESLA uses a 3D residual UNet (ResUNet) for pseudo-CT (pCT) estimation. With a total of 174 participants, we compared PET AC accuracy of DL-TESLA to 3 other methods adopting similar 3D ResUNet structures but using UTE (Formula presented.), or Dixon, or T1-MPRAGE as input. With images from 23 additional participants repeatedly scanned, the test–retest differences and within-subject coefficient of variation of standardized uptake value ratios (SUVR) were compared between PET images reconstructed using either DL-TESLA or CT for AC. Results: DL-TESLA had (1) significantly lower mean absolute error in pCT, (2) the highest Dice coefficients in both bone and air, (3) significantly lower PET relative absolute error in whole brain and various brain regions, (4) the highest percentage of voxels with a PET relative error within both ±3% and ±5%, (5) similar to CT test–retest differences in SUVRs from the cerebrum and mean cortical (MC) region, and (6) similar to CT within-subject coefficient of variation in cerebrum and MC. Conclusion: DL-TESLA demonstrates excellent PET/MR AC accuracy and test–retest repeatability. © 2021 International Society for Magnetic Resonance in Medicine
Author Keywords
attenuation correction; deep learning; Dixon; MR/CT conversion; PET/MR; UTE
Funding details
National Institutes of HealthNIHUL1TR002345
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Let’s Gamble: How a Poor Visualization Can Elicit Risky Behavior” (2020) Proceedings – 2020 IEEE Visualization Conference, VIS 2020
Let’s Gamble: How a Poor Visualization Can Elicit Risky Behavior
(2020) Proceedings – 2020 IEEE Visualization Conference, VIS 2020, art. no. 9331315, pp. 196-200.
Bancilhon, M., Liu, Z., Ottley, A.
Washington University in St. Louis
Abstract
Data visualizations are standard tools for assessing and communicating risks. However, it is not always clear which designs are optimal or how encoding choices might influence risk perception and decision-making. In this paper, we report the findings of a large-scale gambling game that immersed participants in an environment where their actions impacted their bonuses. Participants chose to either enter a lottery or receive guaranteed monetary gains based on five visualization designs. By measuring risk perception and observing decision-making, we present suggestive evidence that people were more likely to gamble when presented area proportioned triangle and circle designs. Using our results, we model risk perception and discuss how our findings can improve visualization selection. © 2020 IEEE.
Author Keywords
Decision Theory; Evaluation methods; Human-centered computing; Risk Behavior; Visualization
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus